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Erdei V, Mészár Z, Varga A. The Burning Pain Transcriptome in the Mouse Primary Somatosensory Cortex. Int J Mol Sci 2025; 26:3538. [PMID: 40332032 PMCID: PMC12027419 DOI: 10.3390/ijms26083538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/21/2025] [Accepted: 04/08/2025] [Indexed: 05/08/2025] Open
Abstract
Our previous research has demonstrated that the spinal cord undergoes epigenetic and molecular alterations following non-severe burn injury (BI). However, the primary somatosensory cortex (S1), crucial for pain perception, remains unexplored in this context. Here, we investigated transcriptomic alterations in the S1 cortex of mice subjected to BI or formalin application (FA) to the hind paw, utilizing RNA sequencing (RNA-seq) one hour after injury. RNA-seq identified 1116 differentially expressed genes (DEGs) in BI and 136 DEGs in formalin-induced inflammatory pain. Notably, 82.4% of DEGs in BI and 32.4% in FA were downregulated. A total of 42 upregulated and 17 downregulated overlapping DEGs were identified, indicating significant differences in the cortical processing of pain based on its origins. Gene Ontology analysis reveals that BI upregulated mitochondrial functions and ribosome synthesis, whereas axon guidance, synaptic plasticity, and neurotransmission-related processes were downregulated. By contrast, formalin treatment mainly impacted metabolic processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlights the significance of retrograde endocannabinoid signaling (REC) in the response to burn injury. These findings demonstrate that transcriptomic remodeling in the S1 cortex is dependent on the sensory modality and suggest that the REC network is activated during acute pain responses following BI.
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Affiliation(s)
- Virág Erdei
- Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (V.E.); (Z.M.)
- Department of Radiology, Central Hospital of Northern Pest—Military Hospital, Budapest, H-1134 Budapest, Hungary
| | - Zoltán Mészár
- Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (V.E.); (Z.M.)
| | - Angelika Varga
- Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary; (V.E.); (Z.M.)
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Di Napoli A, Pasquini L, Visconti E, Vaccaro M, Rossi-Espagnet MC, Napolitano A. Gut-brain axis and neuroplasticity in health and disease: a systematic review. LA RADIOLOGIA MEDICA 2025; 130:327-358. [PMID: 39718685 DOI: 10.1007/s11547-024-01938-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 11/26/2024] [Indexed: 12/25/2024]
Abstract
The gut microbiota emerged as a potential modulator of brain connectivity in health and disease. This systematic review details current evidence on the gut-brain axis and its influence on brain connectivity. The initial set of studies included 532 papers, updated to January 2024. Studies were selected based on employed techniques. We excluded reviews, studies without connectivity focus, studies on non-human subjects. Forty-nine papers were selected. Employed techniques in healthy subjects included 15 functional magnetic resonance imaging studies (fMRI), 5 diffusion tensor imaging, (DTI) 1 electroencephalography (EEG), 6 structural magnetic resonance imaging, 2 magnetoencephalography, 1 spectroscopy, 2 arterial spin labeling (ASL); in patients 17 fMRI, 6 DTI, 2 EEG, 9 structural MRI, 1 transcranial magnetic stimulation, 1 spectroscopy, 2 R2*MRI. In healthy subjects, the gut microbiota was associated with connectivity of areas implied in cognition, memory, attention and emotions. Among the tested areas, amygdala and temporal cortex showed functional and structural differences based on bacteria abundance, as well as frontal and somatosensory cortices, especially in patients with inflammatory bowel syndrome. Several studies confirmed the connection between microbiota and brain functions in healthy subjects and patients affected by gastrointestinal to renal and psychiatric diseases.
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Affiliation(s)
- Alberto Di Napoli
- Neuroradiology Unit, NESMOS Department, Sant'Andrea Hospital, La Sapienza University, 00189, Rome, Italy
| | - Luca Pasquini
- Radiology Department, Memorial Sloan Kettering Cancer Center, New York City, 10065, USA.
- Radiology Department, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, 06510, USA.
| | | | - Maria Vaccaro
- Medical Physics Department, Bambino Gesù Children's Hospital, 00165, Rome, Italy
| | | | - Antonio Napolitano
- Medical Physics Department, Bambino Gesù Children's Hospital, 00165, Rome, Italy
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3
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García Mansilla MJ, Rodríguez Sojo MJ, Lista AR, Ayala Mosqueda CV, Ruiz Malagón AJ, Gálvez J, Rodríguez Nogales A, Rodríguez Sánchez MJ. Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential Therapeutic Effects of Probiotics and Their Metabolites. Nutrients 2024; 17:155. [PMID: 39796588 PMCID: PMC11723002 DOI: 10.3390/nu17010155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
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Affiliation(s)
- María José García Mansilla
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
| | - María Jesús Rodríguez Sojo
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - Andrea Roxana Lista
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | | | - Antonio Jesús Ruiz Malagón
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Málaga, Spain
| | - Julio Gálvez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
- CIBER de Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alba Rodríguez Nogales
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
| | - María José Rodríguez Sánchez
- Department of Pharmacology, Centro de investigación Biomédica (CIBM), University of Granada, 18071 Granada, Spain; (M.J.G.M.); (M.J.R.S.); (J.G.); (A.R.N.); (M.J.R.S.)
- Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; (A.R.L.); (C.V.A.M.)
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Zhang RN, Wang YD, Wang HJ, Ke YQ, Shen XD, Huang L, Lin JJ, He WT, Zhao C, Li ZL, Mao R, Wang YJ, Yang G, Li XH. Identification of neural alterations in patients with Crohn's disease with a novel multiparametric brain MRI-based radiomics model. Insights Imaging 2024; 15:289. [PMID: 39613905 DOI: 10.1186/s13244-024-01859-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 11/06/2024] [Indexed: 12/01/2024] Open
Abstract
OBJECTIVES Gut-brain axis dysfunction has emerged as a key contributor to the pathogenesis of Crohn's disease (CD). The elucidation of neural alterations may provide novel insights into its management. We aimed to develop a multiparameter brain MRI-based radiomics model (RM) for characterizing neural alterations in CD patients and to interpret these alterations using multiomics traits. METHODS This prospective study enrolled 230 CD patients and 46 healthy controls (HCs). Participants voluntarily underwent brain MRI and psychological assessment (n = 155), blood metabolomics analysis (n = 260), and/or fecal 16S rRNA sequencing (n = 182). The RM was developed using 13 features selected from 13,870 first-order features extracted from multiparameter brain MRI in training cohort (CD, n = 75; HCs, n = 32) and validated in test cohort (CD, n = 34; HCs, n = 14). Multiomics data (including gut microbiomics, blood metabolomics, and brain radiomics) were compared between CD patients and HCs. RESULTS In the training cohort, area under the receiver operating characteristic curve (AUC) of RM for distinguishing CD patients from HCs was 0.991 (95% confidence interval (CI), 0.975-1.000). In test cohort, RM showed an AUC of 0.956 (95% CI, 0.881-1.000). CD-enriched blood metabolites such as triacylglycerol (TAG) exhibited significant correlations with both brain features detected by RM and CD-enriched microbiota (e.g., Veillonella). One notable correlation was found between Veillonella and Ctx-Lh-Middle-Temporal-CBF-p90 (r = 0.41). Mediation analysis further revealed that dysbiosis, such as of Veillonella, may regulate the blood flow in the middle temporal cortex through TAG. CONCLUSION We developed a multiparameter MRI-based RM that characterized the neural alterations of CD patients, and multiomics data offer potential evidence to support the validity of our model. Our study may offer clues to help provide potential therapeutic targets. CRITICAL RELEVANCE STATEMENT Our brain-gut axis study developed a novel model using multiparameter MRI and radiomics to characterize brain changes in patients with Crohn's disease. We validated this model's effectiveness using multiomics data, making it a potential biomarker for better patient management. KEY POINTS Utilizing multiparametric MRI and radiomics techniques could unveil Crohn's disease's neurophenotype. The neurophenotype radiomics model is interpreted using multiomics data. This model may serve as a novel biomarker for Crohn's disease management.
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Affiliation(s)
- Ruo-Nan Zhang
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Yang-di Wang
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Hai-Jie Wang
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Dongchuan Road, Minhang District, Shanghai, 200241, People's Republic of China
| | - Yao-Qi Ke
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Xiao-di Shen
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Li Huang
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Jin-Jiang Lin
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Wei-Tao He
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Chen Zhao
- MR Research Collaboration Team, Siemens Healthineers, Guangzhou, People's Republic of China
| | - Zhou-Lei Li
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Ren Mao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Ye-Jun Wang
- Youth Innovation Team of Medical Bioinformatics, Shenzhen University Medical School, Shenzhen, 518060, People's Republic of China
- Department of Cell Biology and Genetics, College of Basic Medicine, Shenzhen University Medical School, Shenzhen, 518060, People's Republic of China
| | - Guang Yang
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Dongchuan Road, Minhang District, Shanghai, 200241, People's Republic of China.
| | - Xue-Hua Li
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
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Huang Y, Zheng E, Hu M, Yang X, Lan Q, Yu Y, Xu B. The impact of depression-mediated gut microbiota composition on Irritable Bowel Syndrome: A Mendelian study. J Affect Disord 2024; 360:15-25. [PMID: 38801922 DOI: 10.1016/j.jad.2024.05.119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 05/29/2024]
Abstract
OBJECTIVE This study uses a two-sample Mendelian randomization (MR) analysis to delineate the causal influence of gut microbiota on the occurrence of irritable bowel syndrome (IBS), concurrently assessing the potential mediating function of depression within this framework. METHODS Several two-sample MR methods were used to assess the causal repercussions of gut microbiota on the onset of both IBS and depression. Following this, gut microbiota and depression, which demonstrated notable causal associations, were integrated as exposure variables in a multivariable Mendelian randomization (MVMR) framework to construct a model encompassing gut microbiota, depression, and IBS. Mediation effects were assessed by examining the indirect pathway of gut microbiota → depression → IBS. RESULTS Two-sample MR analysis unveiled a statistically significant causal association (P < 0.05) between specific bacterial group within the gut microbiota, notably p_Actinobacteria(OR = 0.829225), c_Clostridia(OR = 0.798897), s_Desulfovibrio_piger(OR = 1.163912), g_Streptococcus(OR = 1.132735), c_Actinobacteria(OR = 0.829224), and the onset of IBS. In the MVMR analysis, the relationship between depression and IBS was significant across Model 3, Model 7, Model 8, and Model 13 (P < 0.05). Assessment of mediation effects revealed that c_Clostridia and o_Clostridiales indirectly impacted IBS through depression, with masking effect ratios of 168.46 % and 168.44 %, respectively. CONCLUSION These findings underscore a resilient causal association between the composition of gut microbiota and the initiation of IBS. Furthermore, depression serves as a mediator for particular groups of gut bacteria, thereby contributing to the development of IBS. These observations imply that interventions targeting mental health may potentially alleviate the risk of IBS onset attributable to adverse configurations of gut microbiota.
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Affiliation(s)
- Yi Huang
- Department of General Surgery, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Endian Zheng
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Mei Hu
- Postgraduate training base Alliance of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Xinxin Yang
- Department of Infectious Diseases, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Qiaoli Lan
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China
| | - Yingcong Yu
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China.
| | - Beibei Xu
- Department of Gastroenterology, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, Wenzhou 325000, Zhejiang, China.
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Tsai CF, Chuang CH, Tu PC, Chang WC, Wang YP, Liu PY, Wu PS, Lin CY, Lu CL. Interaction of the gut microbiota and brain functional connectivity in late-life depression. J Psychiatry Neurosci 2024; 49:E289-E300. [PMID: 39299780 PMCID: PMC11426387 DOI: 10.1503/jpn.240050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 07/26/2024] [Accepted: 07/30/2024] [Indexed: 09/22/2024] Open
Abstract
BACKGROUND Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD). METHODS We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms. RESULTS We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of Enterobacter, Akkermansiaceae, Hemophilus, Burkholderia, and Rothia was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of Enterobacter (dominant genus among patients with LLD) was positively correlated with both HAMD scores (r = 0.49, p = 0.0004) and group-characterized FC (r = -0.37, p < 0.05), while Odoribacter (dominant genus among controls) was negatively correlated with both HAMD scores (r = -0.30, p = 0.04) and group-characterized FC. LIMITATIONS The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses. CONCLUSION We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.
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Affiliation(s)
- Chia-Fen Tsai
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Chia-Hsien Chuang
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Pei-Chi Tu
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Wan-Chen Chang
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Yen-Po Wang
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Pei-Yi Liu
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Po-Shan Wu
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Chung-Yen Lin
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
| | - Ching-Liang Lu
- From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
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7
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Simpson JB, Walker ME, Sekela JJ, Ivey SM, Jariwala PB, Storch CM, Kowalewski ME, Graboski AL, Lietzan AD, Walton WG, Davis KA, Cloer EW, Borlandelli V, Hsiao YC, Roberts LR, Perlman DH, Liang X, Overkleeft HS, Bhatt AP, Lu K, Redinbo MR. Gut microbial β-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics. Cell Host Microbe 2024; 32:925-944.e10. [PMID: 38754417 PMCID: PMC11176022 DOI: 10.1016/j.chom.2024.04.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 03/18/2024] [Accepted: 04/24/2024] [Indexed: 05/18/2024]
Abstract
Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial β-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation. We demonstrate that a range of FDA-approved drugs prevent this reactivation by intercepting the catalytic cycle of the enzymes in a conserved fashion. Finally, we find that inhibiting GUS in conventional mice reduces free serotonin and increases its inactive glucuronide in the serum and intestines. Our results illuminate the indispensability of gut microbial enzymes in sustaining endobiotic homeostasis and indicate that therapeutic disruptions of this metabolism promote interindividual response variabilities.
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Affiliation(s)
- Joshua B Simpson
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
| | - Morgan E Walker
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
| | - Joshua J Sekela
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
| | - Samantha M Ivey
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
| | - Parth B Jariwala
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
| | - Cameron M Storch
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
| | - Mark E Kowalewski
- Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA
| | - Amanda L Graboski
- Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA
| | - Adam D Lietzan
- Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - William G Walton
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
| | - Kacey A Davis
- Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA
| | - Erica W Cloer
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Valentina Borlandelli
- Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
| | - Yun-Chung Hsiao
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Lee R Roberts
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA
| | - David H Perlman
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA
| | - Xue Liang
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA
| | - Hermen S Overkleeft
- Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
| | - Aadra P Bhatt
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Kun Lu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Matthew R Redinbo
- Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA.
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8
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Cao B, Xu Q, Shi Y, Zhao R, Li H, Zheng J, Liu F, Wan Y, Wei B. Pathology of pain and its implications for therapeutic interventions. Signal Transduct Target Ther 2024; 9:155. [PMID: 38851750 PMCID: PMC11162504 DOI: 10.1038/s41392-024-01845-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 04/08/2024] [Accepted: 04/25/2024] [Indexed: 06/10/2024] Open
Abstract
Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.
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Affiliation(s)
- Bo Cao
- Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
| | - Qixuan Xu
- Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Yajiao Shi
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, 100191, China
| | - Ruiyang Zhao
- Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Hanghang Li
- Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Jie Zheng
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, 100191, China
| | - Fengyu Liu
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, 100191, China.
| | - You Wan
- Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, 100191, China.
| | - Bo Wei
- Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.
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9
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Niu X, Peng Y, Jiang Z, Huang S, Liu R, Zhu M, Shi L. Gamma-band-based dynamic functional connectivity in pigeon entopallium during sample presentation in a delayed color matching task. Cogn Neurodyn 2024; 18:37-47. [PMID: 38406198 PMCID: PMC10881935 DOI: 10.1007/s11571-022-09916-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 10/12/2022] [Accepted: 11/17/2022] [Indexed: 01/09/2023] Open
Abstract
Birds have developed visual cognitions, especially in discriminating colors due to their four types of cones in the retina. The entopallium of birds is thought to be involved in the processing of color information during visual cognition. However, there is a lack of understanding about how functional connectivity in the entopallium region of birds changes during color cognition, which is related to various input colors. We therefore trained pigeons to perform a delayed color matching task, in which two colors were randomly presented in sample stimuli phrases, and the neural activity at individual recording site and the gamma band functional connectivity among local population in entopallium during sample presentation were analyzed. Both gamma band energy and gamma band functional connectivity presented dynamics as the stimulus was presented and persisted. The response features in the early-stimulus phase were significantly different from those of baseline and the late-stimulus phase. Furthermore, gamma band energy showed significant differences between different colors during the early-stimulus phase, but the global feature of the gamma band functional network did not. Further decoding results showed that decoding accuracy was significantly enhanced by adding functional connectivity features, suggesting the global feature of the gamma band functional network did not directly contain color information, but was related to it. These results provided insight into information processing rules among local neuronal populations in the entopallium of birds during color cognition, which is important for their daily life.
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Affiliation(s)
- Xiaoke Niu
- Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical and Information Engineering, ZhengZhou University, Zhengzhou, 450001 China
| | - Yanyan Peng
- Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical and Information Engineering, ZhengZhou University, Zhengzhou, 450001 China
| | - Zhenyang Jiang
- Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical and Information Engineering, ZhengZhou University, Zhengzhou, 450001 China
| | - Shuman Huang
- Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical and Information Engineering, ZhengZhou University, Zhengzhou, 450001 China
| | - Ruibin Liu
- Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical and Information Engineering, ZhengZhou University, Zhengzhou, 450001 China
| | - Minjie Zhu
- Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical and Information Engineering, ZhengZhou University, Zhengzhou, 450001 China
| | - Li Shi
- Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical and Information Engineering, ZhengZhou University, Zhengzhou, 450001 China
- Department of Automation, Tsinghua University, Beijing, 100000 China
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10
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Liang L, Li S, Huang Y, Zhou J, Xiong D, Li S, Li H, Zhu B, Li X, Ning Y, Hou X, Wu F, Wu K. Relationships among the gut microbiome, brain networks, and symptom severity in schizophrenia patients: A mediation analysis. Neuroimage Clin 2024; 41:103567. [PMID: 38271852 PMCID: PMC10835015 DOI: 10.1016/j.nicl.2024.103567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 01/12/2024] [Accepted: 01/12/2024] [Indexed: 01/27/2024]
Abstract
The microbiome-gut-brain axis (MGBA) plays a critical role in schizophrenia (SZ). However, the underlying mechanisms of the interactions among the gut microbiome, brain networks, and symptom severity in SZ patients remain largely unknown. Fecal samples, structural and functional magnetic resonance imaging (MRI) data, and Positive and Negative Syndrome Scale (PANSS) scores were collected from 38 SZ patients and 38 normal controls, respectively. The data of 16S rRNA gene sequencing were used to analyze the abundance of gut microbiome and the analysis of human brain networks was applied to compute the nodal properties of 90 brain regions. A total of 1,691,280 mediation models were constructed based on 261 gut bacterial, 810 nodal properties, and 4 PANSS scores in SZ patients. A strong correlation between the gut microbiome and brain networks (r = 0.89, false discovery rate (FDR) -corrected p < 0.05) was identified. Importantly, the PANSS scores were linearly correlated with both the gut microbiome (r = 0.5, FDR-corrected p < 0.05) and brain networks (r = 0.59, FDR-corrected p < 0.05). The abundance of genus Sellimonas significantly affected the PANSS negative scores of SZ patients via the betweenness centrality of white matter networks in the inferior frontal gyrus and amygdala. Moreover, 19 significant mediation models demonstrated that the nodal properties of 7 brain regions, predominately from the systems of visual, language, and control of action, showed significant mediating effects on the PANSS scores with the gut microbiome as mediators. Together, our findings indicated the tripartite relationships among the gut microbiome, brain networks, and PANSS scores and suggested their potential role in the neuropathology of SZ.
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Affiliation(s)
- Liqin Liang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China
| | - Shijia Li
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; Swammerdam Institute for Life Sciences (SILS), University of Amsterdam, Amsterdam, The Netherlands
| | - Yuanyuan Huang
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China
| | - Jing Zhou
- School of Material Science and Engineering, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China
| | - Dongsheng Xiong
- School of Material Science and Engineering, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China
| | - Shaochuan Li
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China; Realmeta Technology (Guangzhou) Co., Ltd, Guangzhou 510535, China
| | - Hehua Li
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China
| | - Baoyuan Zhu
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China
| | - Xiaobo Li
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA
| | - Yuping Ning
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China
| | - Xiaohui Hou
- Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou 510500, China.
| | - Fengchun Wu
- Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China; Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China.
| | - Kai Wu
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
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11
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Mulder D, Aarts E, Arias Vasquez A, Bloemendaal M. A systematic review exploring the association between the human gut microbiota and brain connectivity in health and disease. Mol Psychiatry 2023; 28:5037-5061. [PMID: 37479779 PMCID: PMC11041764 DOI: 10.1038/s41380-023-02146-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 06/02/2023] [Accepted: 06/16/2023] [Indexed: 07/23/2023]
Abstract
A body of pre-clinical evidence shows how the gut microbiota influence brain functioning, including brain connectivity. Linking measures of brain connectivity to the gut microbiota can provide important mechanistic insights into the bi-directional gut-brain communication. In this systematic review, we therefore synthesized the available literature assessing this association, evaluating the degree of consistency in microbiota-connectivity associations. Following the PRISMA guidelines, a PubMed search was conducted, including studies published up to September 1, 2022. We identified 16 studies that met the inclusion criteria. Several bacterial genera, including Prevotella, Bacteroides, Ruminococcus, Blautia, and Collinsella were most frequently reported in association with brain connectivity. Additionally, connectivity of the salience (specifically the insula and anterior cingulate cortex), default mode, and frontoparietal networks were most frequently associated with the gut microbiota, both in terms of microbial diversity and composition. There was no discernible pattern in the association between microbiota and brain connectivity. Altogether, based on our synthesis, there is evidence for an association between the gut microbiota and brain connectivity. However, many findings were poorly replicated across studies, and the specificity of the association is yet unclear. The current studies show substantial inter-study heterogeneity in methodology and reporting, limiting the robustness and reproducibility of the findings and emphasizing the need to harmonize methodological approaches. To enhance comparability and replicability, future research should focus on further standardizing processing pipelines and employing data-driven multivariate analysis strategies.
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Affiliation(s)
- Danique Mulder
- Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands
| | - Esther Aarts
- Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands
| | - Alejandro Arias Vasquez
- Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
| | - Mirjam Bloemendaal
- Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands
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12
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Yang L, Liu G, Li S, Yao C, Zhao Z, Chen N, Zhang P, Shang Y, Wang Y, Zhang D, Tian X, Zhang J, Yao Z, Hu B. Association of aberrant brain network dynamics with gut microbial composition uncovers disrupted brain-gut-microbiome interactions in irritable bowel syndrome: Preliminary findings. Eur J Neurol 2023; 30:3529-3539. [PMID: 36905309 DOI: 10.1111/ene.15776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 02/07/2023] [Accepted: 03/05/2023] [Indexed: 03/12/2023]
Abstract
BACKGROUND AND PURPOSE Growing evidence suggests that abnormalities in brain-gut-microbiome (BGM) interactions are involved in the pathogenesis of irritable bowel syndrome (IBS). Our study aimed to explore alterations in dynamic functional connectivity (DFC), the gut microbiome and the bidirectional interaction in the BGM. METHODS Resting-state functional magnetic resonance imaging (rs-fMRI), fecal samples and clinical chacteristics were collected from 33 IBS patients and 32 healthy controls. We performed a systematic DFC analysis on rs-fMRI. The gut microbiome was analyzed by 16S rRNA gene sequencing. Associations between DFC characteristics and microbial alterations were explored. RESULTS In the DFC analysis, four dynamic functional states were identified. IBS patients exhibited increased mean dwell and fraction time in State 4, and reduced transitions from State 3 to State 1. Aberrant temporal properties in State 4 were only evident when choosing a short window (36 s or 44 s). Decreased functional connectivity (FC) variability was found in State 1 and State 3 in IBS patients, two of which (independent component [IC]51-IC91, IC46-IC11) showed significant correlations with clinical characteristics. Additionally, we identified nine significantly differential abundances in microbial composition. We also found that IBS-related microbiota were associated with aberrant FC variability, although these exploratory results were obtained at an uncorrected threshold of significance. CONCLUSIONS Although future studies are needed to confirm our results, the findings not only provide a new insight into the dysconnectivity hypothesis in IBS from a dynamic perspective, but also establish a possible link between DFC and the gut microbiome, which lays the foundation for future research on disrupted BGM interactions.
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Affiliation(s)
- Lin Yang
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Guangyao Liu
- Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Functional and Molecular Imaging, Lanzhou, China
| | - Shan Li
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Chaofan Yao
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Ziyang Zhao
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Nan Chen
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Pengfei Zhang
- Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, China
| | - Yingying Shang
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Yin Wang
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Dekui Zhang
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, China
| | - Xiaozhu Tian
- National Demonstration Center for Experimental Biology Education, School of Life Science, Lanzhou University, Lanzhou, China
| | - Jing Zhang
- Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, China
- Gansu Province Clinical Research Center for Functional and Molecular Imaging, Lanzhou, China
| | - Zhijun Yao
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
| | - Bin Hu
- Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China
- Joint Research Center for Cognitive Neurosensor Technology of Lanzhou University & Institute of Semiconductors, Chinese Academy of Sciences, Lanzhou, China
- Engineering Research Center of Open Source Software and Real-Time System (Lanzhou University), Ministry of Education, Lanzhou, China
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13
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Crichton M, Marshall S, Marx W, Isenring E, Vázquez-Campos X, Dawson SL, Lohning A. Effect of Ginger Root Powder on Gastrointestinal Bacteria Composition, Gastrointestinal Symptoms, Mental Health, Fatigue, and Quality of Life: A Double-Blind Placebo-Controlled Trial. J Nutr 2023; 153:3193-3206. [PMID: 37690779 DOI: 10.1016/j.tjnut.2023.09.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 08/02/2023] [Accepted: 09/01/2023] [Indexed: 09/12/2023] Open
Abstract
BACKGROUND Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized ginger supplement on gut microbiota has not been tested in humans. OBJECTIVES To determine the effect of a standardized ginger (Zingiber officinale) root powder, compared to placebo, on gastrointestinal bacteria and associated outcomes in healthy adults. METHODS A randomized double-blind placebo-controlled trial allocated participants aged 18 to 30 y to ginger or microcrystalline cellulose (MCC) placebo. The intervention comprised 1.2 g/d of ginger (4 capsules per day totaling 84 mg/d of active gingerols/shogaols) for 14 d following a 1-wk run-in period. Primary outcomes were gastrointestinal community composition, alpha and beta diversity, and differential abundance, measured using 16S rRNA gene sequencing of fecal samples. Secondary outcomes were gastrointestinal symptoms, bowel function, depression, anxiety, stress, fatigue, quality of life, and adverse events. RESULTS Fifty-one participants were enrolled and analyzed (71% female; mean age 25 ± 3 y; ginger: n = 29, placebo: n = 22). There was a greater increase in relative abundance of phylum, Actinobacteria, observed following ginger supplementation compared to placebo (U: 145.0; z: -2.1; P = 0.033). Ginger was associated with a greater abundance of the genera Parabacteroides, Bacillus, Ruminococcaceae incertae sedis, unclassified Bacilli, families Defluviitaleaceae, Morganellaceae, and Bacillaceae as well as lower abundance of the genus Blautia and family Sphingomonadaceae (P < 0.05). An improvement in indigestion symptoms was observed with ginger supplementation (U: 196.0; z: -2.4; P = 0.015). No differences between ginger and placebo groups were found for alpha and beta diversity or other secondary outcomes. No moderate or severe adverse events were reported. CONCLUSIONS Supplementation with ginger root powder was safe and altered aspects of gastrointestinal bacteria composition; however, it did not change alpha- or beta diversity, bowel function, gastrointestinal symptoms, mood, or quality of life in healthy adults. These results provide further understanding regarding the mechanisms of action of ginger supplementation. This trial was registered in the Australia New Zealand Clinical Trials Registry as ACTRN12620000302954p and the Therapeutic Goods Administration as CT-2020-CTN-00380-1.
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Affiliation(s)
- Megan Crichton
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia; Cancer and Palliative Care Outcomes Centre, Centre for Healthcare Transformation, School of Nursing, Faculty of Health, Kelvin Grove, Queensland, Australia.
| | - Skye Marshall
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia; Research Institute for Future Health, Gold Coast, Queensland, Australia
| | - Wolfgang Marx
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia; Deakin University, Food & Mood Centre, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Victoria, Australia
| | - Elizabeth Isenring
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia
| | - Xabier Vázquez-Campos
- NSW Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Kensington, New South Wales, Australia
| | - Samantha L Dawson
- Deakin University, Food & Mood Centre, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, Victoria, Australia
| | - Anna Lohning
- Bond University Nutrition and Dietetics Research Group, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia
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Bloemendaal M, Vlaming P, de Boer A, Vermeulen-Kalk K, Bouman A, Kleefstra T, Arias Vasquez A. The role of the gut microbiota in patients with Kleefstra syndrome. Am J Med Genet B Neuropsychiatr Genet 2023; 192:124-138. [PMID: 36630271 DOI: 10.1002/ajmg.b.32926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 01/12/2023]
Abstract
Kleefstra Syndrome (KS) is a rare monogenetic syndrome, caused by haploinsufficiency of the euchromatic histone methyl transferase 1 (EHMT1) gene, an important regulator of neurodevelopment. The clinical features of KS include intellectual disability, autistic behavior and gastrointestinal problems. The gut microbiota, an important modifier of the gut-brain-axis, may constitute an unexplored mechanism underlying clinical KS variation. We investigated the gut microbiota composition of 23 individuals with KS (patients) and 40 of their family members, to test whether (1) variation in the gut microbiota associates with KS diagnosis and (2) variation within the gut microbiota relates with KS syndrome symptoms. Both alpha and beta diversity of patients were different from their family members. Genus Coprococcus 3 was lower in abundance in patients compared to family members. Moreover, abundance of genus Merdibacter was lower in patients versus family members, but only in participants reporting intestinal complaints. Within the patient group, behavioral problems explained 7% of beta diversity variance. Also, within this group, we detected higher levels of Atopobiaceae - uncultured and Ruminococcaceae Subdoligranulum associated with higher symptom severity. These significant signatures in the gut microbiota composition in patients with KS suggest that microbiota differences are part of the KS phenotype.
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Affiliation(s)
- Mirjam Bloemendaal
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
- Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
| | - Priscilla Vlaming
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
| | - Anneke de Boer
- Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands
| | - Karlijn Vermeulen-Kalk
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
- Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands
| | - Arianne Bouman
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
| | - Tjitske Kleefstra
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
- Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
- Centre of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands
| | - Alejandro Arias Vasquez
- Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
- Department of Psychiatry, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands
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15
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Salmeri N, Sinagra E, Dolci C, Buzzaccarini G, Sozzi G, Sutera M, Candiani M, Ungaro F, Massimino L, Danese S, Mandarino FV. Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together-A Review. Microorganisms 2023; 11:2089. [PMID: 37630649 PMCID: PMC10458414 DOI: 10.3390/microorganisms11082089] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/09/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023] Open
Abstract
Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut-brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.
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Affiliation(s)
- Noemi Salmeri
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Emanuele Sinagra
- Gastroenterology & Endoscopy Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy;
| | - Carolina Dolci
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Giovanni Buzzaccarini
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Giulio Sozzi
- Gynecology/Obstetrics Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy; (G.S.); (M.S.)
| | - Miriam Sutera
- Gynecology/Obstetrics Unit, Fondazione Istituto G. Giglio, Contrada Pietra Pollastra Pisciotto, 90015 Cefalù, Italy; (G.S.); (M.S.)
| | - Massimo Candiani
- Gynecology/Obstetrics Unit, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (C.D.); (G.B.); (M.C.)
| | - Federica Ungaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Luca Massimino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
| | - Francesco Vito Mandarino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, 20132 Milan, Italy; (F.U.); (L.M.); (S.D.); (F.V.M.)
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Song C, Yin Y, Qin Y, Li T, Zeng D, Ju T, Duan F, Zhang Y, Lu W. Acanthopanax senticosus extract alleviates radiation-induced learning and memory impairment based on neurotransmitter-gut microbiota communication. CNS Neurosci Ther 2023; 29 Suppl 1:129-145. [PMID: 36971202 PMCID: PMC10314102 DOI: 10.1111/cns.14134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 12/16/2022] [Accepted: 02/15/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND Acanthopanax senticosus (AS) is a medicinal and food plant with many physiological functions, especially nerve protection. Its extract has many functional components, including polysaccharides, flavonoids, saponins, and amino acids. Our previous study indicated that AS extract protected against nerve damage caused by radiation. However, little is known about the gut-brain axis mechanism of AS and its impact on radiation-induced learning and memory impairment. METHOD In 60 Co-γ ray-irradiated mice, we investigated the changes in behavior, neurotransmitters and gut microbiota after different days of administration of AS extract as a dietary supplement. RESULTS The AS extract improved learning and memory ability in mice, and the neurotransmitter levels in the hippocampus and colon started to change from the 7th day, which accompanied changes of the gut microbiota, a decreased abundance of Helicobacter on the 7th day and an increased abundance of Lactobacillus on the 28th day. Among the marker bacteria, Ruminococcus and Clostridiales were associated with 5-HT synthesis, and Streptococcus were associated with 5-HT and ACH synthesis. In addition, the AS extract increased the tight junction protein, inhibited inflammation levels in colon, and even increased the relative protein expression of BDNF and NF-κB and decreased the relative protein expression of IκBα in the hippocampus of irradiated mice. CONCLUSION These results will lay the foundation for further study on the mechanism of the gut-brain axis of AS in preventing radiation-induced learning and memory impairment.
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Affiliation(s)
- Chen Song
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- School of Chemistry and Chemical EngineeringHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
| | - Yishu Yin
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- School of Chemistry and Chemical EngineeringHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
| | - Yue Qin
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
| | - Tianzhu Li
- ZhenBaoDao Pharmaceutical Co., Ltd150040HarbinChina
| | - Deyong Zeng
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- School of Chemistry and Chemical EngineeringHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
| | - Ting Ju
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- School of Chemistry and Chemical EngineeringHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
| | - Fangyuan Duan
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- School of Chemistry and Chemical EngineeringHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
| | - Yingchun Zhang
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
| | - Weihong Lu
- School of Medicine and HealthHarbin Institute of Technology150001HarbinChina
- National and Local Joint Engineering Laboratory for Synthesis, Transformation and Separation of Extreme Environmental NutrientsHarbin Institute of Technology150001HarbinChina
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17
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Zhang X, Xu W, Zhong W, Zhang W, Yang C, Duan L, Niu H, Dong Y, Liu T, Xia S, Wang B. Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau. J Zhejiang Univ Sci B 2023; 24:823-838. [PMID: 37701958 PMCID: PMC10202748 DOI: 10.1631/jzus.b2200509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 02/09/2023] [Indexed: 05/23/2023]
Abstract
The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.
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Affiliation(s)
- Xingguang Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Wei Xu
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Weilong Zhong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China
| | - Wencheng Zhang
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Cheng Yang
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Lisa Duan
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Haiyan Niu
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Yanmei Dong
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Taotao Liu
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China
| | - Shihai Xia
- Department of Gastroenterology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Hepatopancreatic Fiberosis and Molecular Diagnosis & Treatment, Tianjin 300162, China. ,
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China.
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18
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Sasso J, Ammar RM, Tenchov R, Lemmel S, Kelber O, Grieswelle M, Zhou QA. Gut Microbiome-Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders. ACS Chem Neurosci 2023; 14:1717-1763. [PMID: 37156006 PMCID: PMC10197139 DOI: 10.1021/acschemneuro.3c00127] [Citation(s) in RCA: 65] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 04/24/2023] [Indexed: 05/10/2023] Open
Abstract
Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that the gut and brain are in constant bidirectional communication, of which gut microbiota and its metabolic production are a major component, and form the so-called gut microbiome-brain axis. Disturbances of microbiota homeostasis caused by imbalance in their functional composition and metabolic activities, known as dysbiosis, cause dysregulation of these pathways and trigger changes in the blood-brain barrier permeability, thereby causing pathological malfunctions, including neurological and functional gastrointestinal disorders. In turn, the brain can affect the structure and function of gut microbiota through the autonomic nervous system by regulating gut motility, intestinal transit and secretion, and gut permeability. Here, we examine data from the CAS Content Collection, the largest collection of published scientific information, and analyze the publication landscape of recent research. We review the advances in knowledge related to the human gut microbiome, its complexity and functionality, its communication with the central nervous system, and the effect of the gut microbiome-brain axis on mental and gut health. We discuss correlations between gut microbiota composition and various diseases, specifically gastrointestinal and mental disorders. We also explore gut microbiota metabolites with regard to their impact on the brain and gut function and associated diseases. Finally, we assess clinical applications of gut-microbiota-related substances and metabolites with their development pipelines. We hope this review can serve as a useful resource in understanding the current knowledge on this emerging field in an effort to further solving of the remaining challenges and fulfilling its potential.
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Affiliation(s)
- Janet
M. Sasso
- CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United States
| | - Ramy M. Ammar
- Bayer
Consumer Health, R&D Digestive
Health, Darmstadt 64295, Germany
| | - Rumiana Tenchov
- CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United States
| | - Steven Lemmel
- CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United States
| | - Olaf Kelber
- Bayer
Consumer Health, R&D Digestive
Health, Darmstadt 64295, Germany
| | - Malte Grieswelle
- Bayer
Consumer Health, R&D Digestive
Health, Darmstadt 64295, Germany
| | - Qiongqiong Angela Zhou
- CAS, a division of the American Chemical Society, 2540 Olentangy River Rd, Columbus, Ohio 43202, United States
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Wu L, Gao L, Jin X, Chen Z, Qiao X, Cui X, Gao J, Zhang L. Ethanol Extract of Mao Jian Green Tea Attenuates Gastrointestinal Symptoms in a Rat Model of Irritable Bowel Syndrome with Constipation via the 5-hydroxytryptamine Signaling Pathway. Foods 2023; 12:foods12051101. [PMID: 36900618 PMCID: PMC10000491 DOI: 10.3390/foods12051101] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/17/2023] [Accepted: 02/27/2023] [Indexed: 03/08/2023] Open
Abstract
In a previous study, we demonstrated that the hydro extract of Mao Jian Green Tea (MJGT) promotes gastrointestinal motility. In this study, the effect of MJGT ethanol extract (MJGT_EE) in treating irritable bowel syndrome with constipation (IBS-C) in a rat model constructed via maternal separation combined with an ice water stimulation was investigated. First, a successful model construction was confirmed through the determination of the fecal water content (FWC) and the smallest colorectal distension (CRD) volume. Then, the overall regulatory effects of MJGT_EE on the gastrointestinal tract were preliminarily evaluated through gastric emptying and small intestinal propulsion tests. Our findings indicated that MJGT_EE significantly increased FWC (p < 0.01) and the smallest CRD volume (p < 0.05) and promoted gastric emptying and small intestinal propulsion (p < 0.01). Furthermore, mechanistically, MJGT_EE reduced intestinal sensitivity by regulating the expression of proteins related to the serotonin (5-hydroxytryptamine; 5-HT) pathway. More specifically, it decreased tryptophan hydroxylase (TPH) expression (p < 0.05) and increased serotonin transporter (SERT) expression (p < 0.05), thereby decreasing 5-HT secretion (p < 0.01), activating the calmodulin (CaM)/myosin light chain kinase (MLCK) pathway, and increasing 5-HT4 receptor (5-HT4R) expression (p < 0.05). Moreover, MJGT_EE enhanced the diversity of gut microbiota, increased the proportion of beneficial bacteria, and regulated the number of 5-HT-related bacteria. Flavonoids may play the role of being active ingredients in MJGT_EE. These findings suggest that MJGT_EE could serve as a potential therapeutic pathway for IBS-C.
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Affiliation(s)
- Lei Wu
- Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
- Shanxi Key Laboratory of Minor Crops Germplasm Innovation and Molecular Breeding, College of Life Sciences, Shanxi Agricultural University, Taigu, Jinzhong 030801, China
| | - Liming Gao
- Shanxi Key Laboratory of Minor Crops Germplasm Innovation and Molecular Breeding, College of Life Sciences, Shanxi Agricultural University, Taigu, Jinzhong 030801, China
| | - Xiang Jin
- Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
| | - Zhikang Chen
- Shanxi Key Laboratory of Minor Crops Germplasm Innovation and Molecular Breeding, College of Life Sciences, Shanxi Agricultural University, Taigu, Jinzhong 030801, China
| | - Xutong Qiao
- Shanxi Key Laboratory of Minor Crops Germplasm Innovation and Molecular Breeding, College of Life Sciences, Shanxi Agricultural University, Taigu, Jinzhong 030801, China
| | - Xiting Cui
- Shanxi Key Laboratory of Minor Crops Germplasm Innovation and Molecular Breeding, College of Life Sciences, Shanxi Agricultural University, Taigu, Jinzhong 030801, China
| | - Jianhua Gao
- Shanxi Key Laboratory of Minor Crops Germplasm Innovation and Molecular Breeding, College of Life Sciences, Shanxi Agricultural University, Taigu, Jinzhong 030801, China
- Correspondence: (J.G.); (L.Z.)
| | - Liwei Zhang
- Institute of Molecular Science, Shanxi University, Taiyuan 030006, China
- Correspondence: (J.G.); (L.Z.)
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20
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Hizay A, Dag K, Oz N, Comak-Gocer EM, Ozbey-Unlu O, Ucak M, Keles-Celik N. Lactobacillus acidophilus regulates abnormal serotonin availability in experimental ulcerative colitis. Anaerobe 2023; 80:102710. [PMID: 36708801 DOI: 10.1016/j.anaerobe.2023.102710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 01/06/2023] [Accepted: 01/24/2023] [Indexed: 01/26/2023]
Abstract
OBJECTIVES Probiotics are known to play a beneficial role in curing irritable bowel syndrome such as ulcerative colitis. Commensal Lactobacillus species are thought to play a protective role against ulcerative colitis, as they restore homeostasis in intestinal disorders. Abnormal serotonin availability has been described in ulcerative colitis, but the underlying mechanism is still unclear. The aim of this study was to determine the anti-inflammatory role of Lactobacillus acidophilus (L. acidophilus) and its effect on serotonin expression. METHODS Ulcerative colitis was created with the intrarectal administration of acetic acid. A total of 40 adult male rats were divided into five groups of eight rats as control, sham, experimental colitis, treatment (Colitis + L. acidophilus) and protective group (L. acidophilus + colitis). To evaluate the effects of L. acidophilus on serotonin expression in ulcerative colitis, this bacterial strain was administered orally to the rats with acetic acid-induced colitis. After oral administration of L. acidophilus for 14 days, serotonin content was biochemically measured and serotonin expression was evaluated immunohistochemically. RESULTS The expression of serotonin and its protein content was significantly increased in colitis compared to the control and sham groups. Abnormal serotonin availability in the rats with acetic acid-induced colitis was significantly reduced by the L. acidophilus. CONCLUSIONS In our study, it was observed that the amount of serotonin in the intestinal tissue increased excessively with ulcerative colitis. In addition, L.acidophilus has been found to reduce the abnormally increased amount of serotonin in the colon tissue, as well as reduce the inflammation in the intestinal tissue that occurs with ulcerative colitis. With our findings, it is predicted that probiotic application can be used as a treatment option in ulcerative colitis.
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Affiliation(s)
- Arzu Hizay
- Department of Anatomy, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
| | - Kubra Dag
- Department of Anatomy, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
| | - Nuriye Oz
- Department of Anatomy, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
| | - Emine Mine Comak-Gocer
- Department of Nutrition and Dietetics, Akdeniz University, Faculty of Health Sciences, Antalya, Turkey.
| | - Ozlem Ozbey-Unlu
- Department of Histology and Embryology, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
| | - Melike Ucak
- Department of Histology and Embryology, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
| | - Nigar Keles-Celik
- Department of Anatomy, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
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21
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Bidaki R, Hekmati Moghaddam SH, Sadeh M. Gut Microbiota and Neuropsychiatric Disorders. Basic Clin Neurosci 2023; 14:167-170. [PMID: 37346870 PMCID: PMC10279994 DOI: 10.32598/bcn.2021.3220.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 04/30/2021] [Accepted: 06/27/2021] [Indexed: 06/23/2023] Open
Abstract
Numerous studies in humans and animals hypothesize that gut microbiota dysbiosis is involved in the development of behavioral and neurological diseases such as depression, autism spectrum disorder, Parkinson disease, multiple sclerosis, stroke and Alzheimer's disease. Some of the most salient works so far regarding the brain-gut axis are mentioned below. The current knowledge on the impact of gut microbiota on nervous system diseases is far from being directly used for pharmacologic or nutritional advice toward restoration of normal bodily functions. It seems that a more comprehensive approach should be followed so that the individual effect of each kind of intervention on the patient's somatic or psychological status is determined. Future research must address global need for regimens which could reestablish normal composition of gut microorganisms after each neuropsychological disorder.
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Affiliation(s)
- Reza Bidaki
- Research Center of Addiction and Behavioral Sciences, Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Seyed Hossein Hekmati Moghaddam
- Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Maryam Sadeh
- Department of Laboratory Sciences, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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22
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Shin A, Kashyap PC. Multi-omics for biomarker approaches in the diagnostic evaluation and management of abdominal pain and irritable bowel syndrome: what lies ahead. Gut Microbes 2023; 15:2195792. [PMID: 37009874 PMCID: PMC10072066 DOI: 10.1080/19490976.2023.2195792] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 03/23/2023] [Indexed: 04/04/2023] Open
Abstract
Reliable biomarkers for common disorders of gut-brain interaction characterized by abdominal pain, including irritable bowel syndrome (IBS), are critically needed to enhance care and develop individualized therapies. The dynamic and heterogeneous nature of the pathophysiological mechanisms that underlie visceral hypersensitivity have challenged successful biomarker development. Consequently, effective therapies for pain in IBS are lacking. However, recent advances in modern omics technologies offer new opportunities to acquire deep biological insights into mechanisms of pain and nociception. Newer methods for large-scale data integration of complementary omics approaches have further expanded our ability to build a holistic understanding of complex biological networks and their co-contributions to abdominal pain. Here, we review the mechanisms of visceral hypersensitivity, focusing on IBS. We discuss candidate biomarkers for pain in IBS identified through single omics studies and summarize emerging multi-omics approaches for developing novel biomarkers that may transform clinical care for patients with IBS and abdominal pain.
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Affiliation(s)
- Andrea Shin
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Purna C. Kashyap
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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23
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Hou Y, Dong L, Lu X, Shi H, Xu B, Zhong W, Ma L, Wang S, Yang C, He X, Zhao Y, Wang S. Distinctions Between Fecal and Intestinal Mucosal Microbiota in Subgroups of Irritable Bowel Syndrome. Dig Dis Sci 2022; 67:5580-5592. [PMID: 35879512 DOI: 10.1007/s10620-022-07588-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 04/14/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND AND AIMS Recent studies have shown that changes in the intestinal microbiota contribute to the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the characteristics of the fecal and intestinal mucosal microbiota in IBS patients, and the correlation between microbiota and clinical manifestations. METHODS Fecal and intestinal mucosal samples were collected from 14 constipation-predominant IBS (IBS-C) patients, 20 diarrhea-predominant IBS (IBS-D) patients, and 20 healthy controls (HCs). 16S rRNA gene sequencing and fluorescence in situ hybridization were used for the analysis of samples. RESULTS Community richness and diversity of the fecal microbiota in IBS patients were significantly reduced compared with the HCs. The mucosal samples in IBS patients showed decreased Bifidobacterium and increased Bacteroides caccae compared with HCs; Eubacterium and Roseburia were decreased in IBS-C patients and increased in IBS-D patients. A comparison of the fecal and mucosal microbiota in IBS patients showed significantly increased Bifidobacterium in fecal samples and a decrease in mucosal samples in IBS-C patients; Bacteroides caccae and Roseburia were significantly reduced in fecal samples and increased in mucosal samples of IBS patients. A correlation between microbiota and clinical manifestations in IBS patients showed that Bacteroides caccae and Roseburia in fecal samples and Bifidobacterium and Eubacterium in mucosal samples were associated with abdominal pain and distention. CONCLUSIONS Distinct differences exist between the fecal and intestinal mucosal microbiota in IBS patients, with the changes in the latter appearing more consistent with the pathophysiology of IBS. Changes in intestinal microbiota were associated with the clinical manifestations in IBS.
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Affiliation(s)
- Yangfan Hou
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China.,Pulmonary and Critical Care Medicine, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Lei Dong
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Xiaolan Lu
- Department of Gastroenterology, Shanghai Pudong Hospital, Shanghai, 201399, China
| | - Haitao Shi
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Bing Xu
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Wenting Zhong
- International Medical Ward, Xi'an Jiaotong University Medical College First Affiliated Hospital, Xi'an, 710061, China
| | - Lin Ma
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Shuhui Wang
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Caifeng Yang
- Departments of Gastroenterology, Xi'an City First Hospital, Xi'an, 710002, China
| | - Xinyi He
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Yidi Zhao
- Emergency Department, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China
| | - Shenhao Wang
- Department of Gastroenterology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an, 710004, China.
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24
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Kim CH, Lee YU, Kim KH, Kang S, Kang GH, Chu H, Lee S. Comparison of Metabolites and Gut Microbes between Patients with Ulcerative Colitis and Healthy Individuals for an Integrative Medicine Approach to Ulcerative Colitis—A Pilot Observational Clinical Study (STROBE Compliant). Diagnostics (Basel) 2022; 12:diagnostics12081969. [PMID: 36010319 PMCID: PMC9407185 DOI: 10.3390/diagnostics12081969] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 08/09/2022] [Accepted: 08/14/2022] [Indexed: 12/02/2022] Open
Abstract
Ulcerative colitis (UC) is an intractable disease associated with high morbidity and healthcare costs. Metabolites and gut microbes are areas of interest for mainstream and complementary and alternative medicine. We, therefore, aimed to contribute to the discovery of an integrative medicine for UC by comparing and analyzing gut microbes and metabolites in patients with UC and in healthy individuals. This was an observational case-control study. Blood and stool samples were collected from the participants, and metabolite and gut microbial studies were performed. Among metabolites, formate, glycolate, trimethylamine, valine, and pyruvate levels were significantly different between the two groups. Among gut microbes, the abundance of Bacteroidetes at the phylum level; Bacteroidia at the class level; Bacteroidales and Actinomycetales at the order level; Prevotellaceae, Acidaminococcaceae, and Leptotrichiaceae at the family level; and Prevotella, Roseburia, Paraprevotella, Phascolarctobacterium, Ruminococcus, Coprococcus, Clostridium_XIVB, Atopobium, and Leptotrichia at the genus level was also significantly different. Most of the metabolites and gut microbes significantly different between the two groups were involved in energy metabolism and inflammatory processes, respectively. The results of this study could be helpful for the identification of targets for integrative medicine approaches for UC.
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Affiliation(s)
- Cheol-Hyun Kim
- Department of Internal Medicine and Neuroscience, College of Korean Medicine, Wonkwang University, Iksan 54538, Korea
- Stroke Korean Medicine Research Center, Wonkwang University, Iksan 54538, Korea
- Correspondence: (C.-H.K.); (S.L.); Tel.: +82-10-7169-1625 (C.-H.K.); +82-10-2632-0119 (S.L.)
| | - Young-Ung Lee
- Department of Internal Medicine and Neuroscience, College of Korean Medicine, Wonkwang University, Iksan 54538, Korea
- Stroke Korean Medicine Research Center, Wonkwang University, Iksan 54538, Korea
| | - Kwang-Ho Kim
- Department of Internal Medicine and Neuroscience, College of Korean Medicine, Wonkwang University, Iksan 54538, Korea
- Stroke Korean Medicine Research Center, Wonkwang University, Iksan 54538, Korea
| | - Sunny Kang
- Department of Internal Medicine and Neuroscience, College of Korean Medicine, Wonkwang University, Iksan 54538, Korea
- Stroke Korean Medicine Research Center, Wonkwang University, Iksan 54538, Korea
| | - Geon-Hui Kang
- Stroke Korean Medicine Research Center, Wonkwang University, Iksan 54538, Korea
- Hanbang Cardio-Renal Syndrome Research Center, College of Oriental Medicine, Wonkwang University, Iksan 54538, Korea
| | - Hongmin Chu
- Department of Internal Medicine and Neuroscience, College of Korean Medicine, Wonkwang University, Iksan 54538, Korea
- Stroke Korean Medicine Research Center, Wonkwang University, Iksan 54538, Korea
| | - Sangkwan Lee
- Department of Internal Medicine and Neuroscience, College of Korean Medicine, Wonkwang University, Iksan 54538, Korea
- Stroke Korean Medicine Research Center, Wonkwang University, Iksan 54538, Korea
- Hanbang Cardio-Renal Syndrome Research Center, College of Oriental Medicine, Wonkwang University, Iksan 54538, Korea
- Correspondence: (C.-H.K.); (S.L.); Tel.: +82-10-7169-1625 (C.-H.K.); +82-10-2632-0119 (S.L.)
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Zhang G, Zhang T, Cao Z, Tao Z, Wan T, Yao M, Su X, Wei W. Effects and Mechanisms of Acupuncture on Diarrhea-Predominant Irritable Bowel Syndrome: A Systematic Review. Front Neurosci 2022; 16:918701. [PMID: 35911986 PMCID: PMC9334728 DOI: 10.3389/fnins.2022.918701] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/20/2022] [Indexed: 11/28/2022] Open
Abstract
Background Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with challenging treatment. According to evidence-based studies, acupuncture is likely to be a promising therapy and subservient adjunct for IBS. Mechanism study of acupuncture based on related clinical trials of high quality, nevertheless, is still vacant. Aim This study aims to assess the results and qualities of current clinical evidence and conclude the relevant pathophysiological mechanisms and therapeutic effects of acupuncture on IBS with diarrhea (IBS-D). Methods Literature from four databases, namely, PubMed, Cochrane Library, EMBASE, and Web of Science, was systematically searched to obtain eligible randomized controlled trials (RCTs), which contained mechanism research of acupuncture treatment in IBS-D patients. Two independent reviewers completed data extraction and quality evaluation using the RevMan 5.4.1 software. Results Ten trials that covered 19 items related to mechanism research were included in this review. Acupuncture was reported to improve IBS-D symptoms and quality of life, with positive effects in regulating brain-gut peptides, cerebral activities, neuroendocrine functions, psychological state, and inflammatory GI and hypersensitive intestinal tracts. Conclusion Acupuncture has potential influence on pathophysiology alterations such as regulating brain-gut peptides, altering cerebral connectivity and activity, promoting neuroendocrine functions and mental state, and mitigating inflammation as well as hypersensitivity of bowels in IBS-D patients, but further studies of high quality are still necessary. Systematic Review Registration [https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022320331].
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Affiliation(s)
- Gezhi Zhang
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Tao Zhang
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Zeng Cao
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Zijing Tao
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Tianhao Wan
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Mengxi Yao
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
| | - Xiaolan Su
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
- *Correspondence: Xiaolan Su,
| | - Wei Wei
- Department of Gastroenterology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Beijing, China
- Wei Wei,
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Gu Y, Wang C, Qin X, Zhou B, Liu X, Liu T, Xie R, Liu J, Wang B, Cao H. Saccharomyces boulardii, a yeast probiotic, inhibits gut motility through upregulating intestinal serotonin transporter and modulating gut microbiota. Pharmacol Res 2022; 181:106291. [PMID: 35690329 DOI: 10.1016/j.phrs.2022.106291] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 05/30/2022] [Accepted: 06/05/2022] [Indexed: 11/18/2022]
Abstract
Saccharomyces boulardii (Sb) is a widely used fungal probiotic in treating various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of Sb relieving IBS remain unclear. The abnormal serotonin transporter (SERT) / 5-hydroxytryptamine (5-HT) system could cause disordered gastrointestinal sensation and motility, which closely related to IBS pathogenesis. The aim of this study was to explore the effects and mechanisms of Sb on regulating gut motility. Sb supernatant (SbS) was administered to intestinal epithelial cells and mice. SbS upregulated SERT expression via enhancing heparin-binding epidermal growth factor (HB-EGF) release to activate epidermal growth factor receptor (EGFR). EGFR kinase inhibitor treatment or HB-EGF siRNA transfection in cells blocked SbS upregulating SERT. Consistently, SbS-treated mice presented inhibited gut motility, and EGFR activation and SERT upregulation were found. Moreover, 16 S rDNA sequence presented an evident decrease in Firmicutes / Bacteroidetes ratio in SbS group. In genus level, SbS reduced Escherichia_Shigella, Alistipes, Clostridium XlVa, and Saccharibacteria_genera_incertae_sedis, meanwhile, increased Parasutterella. The abundance of Saccharibacteria_genera_incertae_sedis positively correlated with defecation parameters and intestinal 5-HT content. Fecal microbiota transplantation showed that SbS could modulate gut microbiota to influence gut motility. Interestingly, elimination of gut microbiota with antibiotic cocktail did not entirely block SbS regulating gut motility. Furthermore, SbS administration to IBS-D mice significantly upregulated SERT and inhibited gut motility. In conclusion, SbS could upregulate SERT by EGFR activation, and modulate gut microbiota to inhibit gut motility. This finding would provide more evidence for the application of this yeast probiotic in IBS and other diarrheal disorders.
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Affiliation(s)
- Yu Gu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China
| | - Chen Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China
| | - Xiali Qin
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China
| | - Bingqian Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China
| | - Xiang Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China
| | - Runxiang Xie
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China
| | - Jinghua Liu
- Department of Gastroenterology, Tianjin TeDa Hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China.
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, China.
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Zhang T, Ma X, Tian W, Zhang J, Wei Y, Zhang B, Wang F, Tang X. Global Research Trends in Irritable Bowel Syndrome: A Bibliometric and Visualized Study. Front Med (Lausanne) 2022; 9:922063. [PMID: 35833106 PMCID: PMC9271748 DOI: 10.3389/fmed.2022.922063] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 06/09/2022] [Indexed: 12/15/2022] Open
Abstract
Background There are about 10–23% of adults worldwide suffering from irritable bowel syndrome (IBS). Over the past few decades, there are many aspects of uncertainty regarding IBS leading to an ongoing interest in the topic as reflected by a vast number of publications, whose heterogeneity and variable quality may challenge researchers to measure their scientific impact, to identify collaborative networks, and to grasp actively researched themes. Accordingly, with help from bibliometric approaches, our goal is to assess the structure, evolution, and trends of IBS research between 2007 and 2022. Methods The documents exclusively focusing on IBS from 2007 to 2022 were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. The annual productivity of IBS research, and the most prolific countries or regions, authors, journals and resource-, intellectual- and knowledge-sharing in IBS research, as well as co-citation analysis of references and keywords were analyzed through Microsoft Office Excel 2019, CiteSpace, and VOSviewer. Results In total, 4,092 publications were reviewed. The USA led the list of countries with the most publications (1,226, 29.96%). Mayo Clinic contributed more publications than any other institution (193, 4.71%). MAGNUS SIMREN stood out as the most active and impactful scholar with the highest number of publications and the greatest betweenness centrality value. The most high-yield journal in this field was Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society (275, 6.72%). Gastroenterology had the most co-citations (3,721, 3.60%). Keywords with the ongoing strong citation bursts were chromogranin A, rat model, peptide YY, gut microbiota, and low-FODMAP diet, etc. Conclusion Through bibliometric analysis, we gleaned deep insight into the current status of literature investigating IBS for the first time. These findings will be useful to scholars interested in understanding the key information in the field, as well as identifying possible research frontiers.
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Affiliation(s)
- Tai Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Xiangxue Ma
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Wende Tian
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaqi Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Yuchen Wei
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
| | - Beihua Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- *Correspondence: Beihua Zhang,
| | - Fengyun Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Fengyun Wang,
| | - Xudong Tang
- Xiyuan Hospital, Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, China Academy of Chinese Medical Sciences, Beijing, China
- Xudong Tang,
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Gitajn I, Werth P, O'Toole RV, Joshi M, Jevsevar D, Wise B, Rane A, Horton S, McClure EA, Ross B, Nadell C. Microbial Interspecies Associations in Fracture-Related Infection. J Orthop Trauma 2022; 36:309-316. [PMID: 35703847 DOI: 10.1097/bot.0000000000002314] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/16/2021] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Describe co-occurrence or clustering of microbial taxa in fracture-related infections to inform further exploration of infection-related interactions among them. DESIGN Retrospective review. SETTING Level 1 trauma center. PATIENTS/PARTICIPANTS Four hundred twenty-three patients requiring surgical intervention for deep surgical site infection between January 2006 and December 2015. INTERVENTION None. MAIN OUTCOME MEASUREMENT Connection between microbial taxa. RESULTS Methicillin-resistant Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, and coagulase-negative Staphylococcus represented the majority of monomicrobial observations (71%). Gram-negative rods, gram-positive rods, and anaerobes presented more frequently in polymicrobial infections. Enterobacter, vancomycin-sensitive Enterococcus, and Pseudomonas are present in polymicrobial infections with the highest frequencies and represent the top 3 most important nodes within the microorganism framework, with the highest network centrality scores. CONCLUSIONS The present study indicates that there are common microbial taxa (Enterobacter, Enterococcus, and Pseudomonas) that tend to co-occur with other microbes greater than 75% of the time. These commonly co-occurring microbes have demonstrated interactive relationships in other disease pathologies, suggesting that there may be similar important interactions in fracture-related infections. It is possible that these microbial communities play a role in the persistently high failure rate associated with management of infection after trauma. Future studies are needed to study the intermicrobial interactions that explain the frequency at which taxa co-occur. Understanding and potentially disrupting these intermicrobial relationships could inform improvements in the treatment of established infections and in the prevention of infection in high-risk patients. LEVEL OF EVIDENCE Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Ida Gitajn
- Department of Orthopaedics, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Paul Werth
- Department of Orthopaedics, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Robert V O'Toole
- Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD
| | - Mandarin Joshi
- Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD
| | - David Jevsevar
- Department of Orthopaedics, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Brent Wise
- Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD
| | - Ajinya Rane
- Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD
| | - Steven Horton
- Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD
| | - Emily A McClure
- Department of Microbiology and Immunology, Dartmouth, Geisel School of Medicine, Hanover, NH; and
| | - Benjamin Ross
- Department of Microbiology and Immunology, Dartmouth, Geisel School of Medicine, Hanover, NH; and
| | - Carey Nadell
- Department of Biological Sciences, Dartmouth, Hanover, NH
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Structural and functional neuroimaging of the effects of the gut microbiome. Eur Radiol 2022; 32:3683-3692. [PMID: 35029734 PMCID: PMC9124675 DOI: 10.1007/s00330-021-08486-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 10/20/2021] [Accepted: 11/28/2021] [Indexed: 11/04/2022]
Abstract
Interactions between intestinal microbiota and the central nervous system profoundly influence brain structure and function. Over the past 15 years, intense research efforts have uncovered the significant association between gut microbial dysbiosis and neurologic, neurodegenerative, and psychiatric disorders; however, our understanding of the effect of gut microbiota on quantitative neuroimaging measures of brain microstructure and function remains limited. Many current gut microbiome studies specifically focus on discovering correlations between specific microbes and neurologic disease states that, while important, leave critical mechanistic questions unanswered. To address this significant gap in knowledge, quantitative structural and functional brain imaging has emerged as a vital bridge and as the next step in understanding how the gut microbiome influences the brain. In this review, we examine the current state-of-the-art, raise awareness of this important topic, and aim to highlight immense new opportunities-in both research and clinical imaging-for the imaging community in this emerging field of study. Our review also highlights the potential for preclinical imaging of germ-free and gnotobiotic models to significantly advance our understanding of the causal mechanisms by which the gut microbiome alters neural microstructure and function. KEY POINTS: • Alterations to the gut microbiome can significantly influence brain structure and function in health and disease. • Quantitative neuroimaging can help elucidate the effect of gut microbiota on the brain and with future translational advances, neuroimaging will be critical for both diagnostic assessment and therapeutic monitoring.
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Liu X, Du ZR, Wang X, Sun XR, Zhao Q, Zhao F, Wong WT, Wong KH, Dong XL. Polymannuronic acid prebiotic plus Lacticaseibacillus rhamnosus GG probiotic as a novel synbiotic promoted their separate neuroprotection against Parkinson’s disease. Food Res Int 2022; 155:111067. [DOI: 10.1016/j.foodres.2022.111067] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 02/21/2022] [Accepted: 02/22/2022] [Indexed: 12/18/2022]
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Shin JH, Lee JW, Lim SH, Yoon BW, Lee Y, Seo JH. The microbiomes of the eyelid and buccal area of patients with uveitic glaucoma. BMC Ophthalmol 2022; 22:170. [PMID: 35421938 PMCID: PMC9012020 DOI: 10.1186/s12886-022-02395-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 04/11/2022] [Indexed: 02/08/2023] Open
Abstract
Background The microbiome could trigger inflammation leading to epigenetic changes and is involved in the pathophysiology of eye diseases; however, its effect on uveitic glaucoma (UG) has not been fully investigated. This study analysed the differences in eyelid and buccal microbiomes in patients with UG using next-generation sequencing. Methods The eyelid and buccal specimens of 34 UG and 25 control patients were collected. The taxonomic composition of the microbiome was obtained via 16S ribosomal DNA sequencing. Diversity and differential gene expression analyses (DEG) determined taxon differences between the microbiomes of UG and control groups. Results In both the eyelid and buccal microbiomes, alpha-diversity was lower in UG patients than controls, while beta-diversity in patients with UG was higher than in controls. DEG analysis of the eyelid microbiome revealed various taxa differences, including enrichment of Paenibacillus and Dermacoccus (p-value, 1.31e−6 and 1.55e−7, respectively) and depletion of Morganella and Lactococcus (p-value, 6.26e−12 and 2.55e−6, respectively) in patients with UG. In the buccal microbiome, taxa such as Lactococcus was significantly depleted (p-value, 1.31e−17), whereas Faecalibacterium was enriched in patients with UG (p-value, 6.12e−8). Conclusions The eyelid and buccal microbiomes in patients with UG differ from controls, which raises concerns surrounding environmental influences on the pathogenesis of UG. The reduced Lactococcus in the eyelid and buccal area suggest that microbiota dysbiosis is associated with UG.
Supplementary Information The online version contains supplementary material available at 10.1186/s12886-022-02395-x.
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Abstract
PURPOSE OF REVIEW Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. The diagnosis of IBS is based on the presence of defined clinical Rome IV criteria in the absence of alarm features. The majority of patients with IBS report of food triggers eliciting typical IBS symptoms and trying to modify their dietary intake. RECENT FINDINGS FGID including IBS are defined as disorders of the gut-brain interaction. A large proportion of individuals with IBS link their symptoms to dietary factors, and recent clinical studies have shown benefits of a diet low in FODMAPs (Fermentable Oligo-, Di-, and Monosaccharides and Polyols) on IBS symptoms and quality of life. Dietary interventions mediate directly changes of luminal gut contents affecting chemosensing-enteroendocrine cells in the modulation of the gut brain microbiome axis in IBS patients. Long-term assessment of clinical outcomes in patients on a low FODMAP diet is needed. Professional guidelines have incorporated the suggestion to offer IBS patients a diet low in FODMAPs. SUMMARY The FGIDs, including IBS, are defined as gut-brain disorders. Low FODMAP diet has been shown in clinical trials to reduce IBS symptoms but long-term efficacy and nutritional side-effects remain uncertain.
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Affiliation(s)
- H Christian Weber
- Section of Gastroenterology, Boston University School of Medicine
- Section of Gastroenterology and Hepatology, VA Boston Healthcare System, Boston, Massachusetts, USA
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Sumich A, Heym N, Lenzoni S, Hunter K. Gut microbiome-brain axis and inflammation in temperament, personality and psychopathology. Curr Opin Behav Sci 2022. [DOI: 10.1016/j.cobeha.2022.101101] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Zhu J, Wang C, Qian Y, Cai H, Zhang S, Zhang C, Zhao W, Zhang T, Zhang B, Chen J, Liu S, Yu Y. Multimodal neuroimaging fusion biomarkers mediate the association between gut microbiota and cognition. Prog Neuropsychopharmacol Biol Psychiatry 2022; 113:110468. [PMID: 34736997 DOI: 10.1016/j.pnpbp.2021.110468] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/25/2021] [Accepted: 10/29/2021] [Indexed: 02/06/2023]
Abstract
Background The field of microbiota-gut-brain research in animals has progressed, while the exact nature of gut microbiota-brain-cognition relationship in humans is not completely elucidated, likely due to small sample sizes and single neuroimaging modality utilized to delineate limited aspects of the brain. We aimed to comprehensively investigate such association in a large sample using multimodal MRI. Methods Fecal samples were collected from 157 healthy young adults and 16S sequencing was used to assess gut microbial diversity and enterotypes. Five brain imaging measures, including regional homogeneity (ReHo) and functional connectivity density (FCD) from resting-state functional MRI, cerebral blood flow (CBF) from arterial spin labeling, gray matter volume (GMV) from structural MRI, and fractional anisotropy (FA) from diffusion tensor imaging, were jointly analyzed with a data-driven multivariate fusion method. Cognition was evaluated by 3-back and digit span tasks. Results We found significant associations of gut microbial diversity with ReHo, FCD, CBF, and GMV within the frontoparietal, default mode and visual networks, as well as with FA in a distributed set of juxtacortical white matter regions. In addition, there were FCD, CBF, GMV, and FA differences between Prevotella- versus Bacteroides-enterotypes in females and between Prevotella- versus Ruminococcaceae-enterotypes in males. Moreover, the identified neuroimaging fusion biomarkers could mediate the associations between microbial diversity and cognition. Conclusions Our findings not only expand existing knowledge of the microbiota-gut-brain axis, but also have potential clinical and translational implications by exposing the gut microbiota as a promising treatment and prevention target for cognitive impairment and related brain disorders.
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Affiliation(s)
- Jiajia Zhu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Chunli Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - Yinfeng Qian
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Huanhuan Cai
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Shujun Zhang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Cun Zhang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Wenming Zhao
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Tingting Zhang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Biao Zhang
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Jingyao Chen
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Siyu Liu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China
| | - Yongqiang Yu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China.
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Wang M, Amakye WK, Gong C, Ren Z, Yuan E, Ren J. Effect of oral and intraperitoneal administration of walnut-derived pentapeptide PW5 on cognitive impairments in APP SWE/PS1 ΔE9 mice. Free Radic Biol Med 2022; 180:191-197. [PMID: 35077820 DOI: 10.1016/j.freeradbiomed.2022.01.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/23/2021] [Accepted: 01/04/2022] [Indexed: 12/22/2022]
Abstract
Food-derived bioactive peptides, encrypted in native protein sequence, have attracted enormous research attention due to its potential in the prevention and/or treatment of a broad range of diseases. However, administration route poses a great challenge to their development and commercial applications. Patient-friendly delivery of bioactive peptides which also enhances its efficacy urgently remain to be addressed. Here we compared the effects of oral administration (PO) to intraperitoneal injection (IP) of a walnut-derived bioactive pentapeptide PW5 (Pro-Pro-Lys-Asn-Trp) in cognitive improvement capacity in APPSWE/PS1ΔE9 transgenic mice. Strikingly, we found that only PO administration of PW5 could effectively ameliorate cognitive impairments and reduce the β-amyloid deposits in the brain compared to the IP administration. This may be attributable to alterations in the gut microbiota communities, including alterations in microbial α- and β-diversities after PO treatment, leading to the reversal of the relative abundances of ten differential genera (e.g. Acinetobacter, Lactobacillus, Akkermansia, Allobaculum, Adlercreutzia, Coriobacteriaceae, unclassified_p_ Firmicutes, Desulfovibrionaceae, Oscillospira and Anaeroplasma) which are highly correlated with disease progression. Thus, this study has leveraged on PW5 to proof the superior efficacy of oral delivery to injection delivery in improving cognitive impairments in vivo, suggesting that oral delivery might be highly recommended as a prioritized delivery route in the development of food-derived peptides.
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Affiliation(s)
- Min Wang
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510641, China
| | - William Kwame Amakye
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510641, China
| | - Congcong Gong
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510641, China
| | - Zhengyu Ren
- College of Pharmacology, University of South China, Hengyang, Hunan, 421001, China
| | - Erdong Yuan
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510641, China
| | - Jiaoyan Ren
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong, 510641, China; Research Institute for Food Nutrition and Human Health, Guangzhou, China.
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Frändemark Å, Törnblom H, Simrén M, Jakobsson S. Maintaining work life under threat of symptoms: a grounded theory study of work life experiences in persons with Irritable Bowel Syndrome. BMC Gastroenterol 2022; 22:73. [PMID: 35183112 PMCID: PMC8858507 DOI: 10.1186/s12876-022-02158-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 02/15/2022] [Indexed: 12/31/2022] Open
Abstract
Background Irritable Bowel Syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Earlier studies have shown that IBS can limit the ability to perform at work and lead to absenteeism. However, few studies focus on work life experiences based on patients’ narratives. The purpose of this study was to construct a theory for how persons with IBS maintain their work life. Methods A qualitative study was performed using constructivist grounded theory. Semi-structured interviews with 15 women and 8 men with IBS (26–64 years of age) were conducted. Fourteen participants worked full-time, six worked part-time and three were on sick leave. The interviews were transcribed verbatim and coded line-by-line, incident-by-incident and thereafter focused coding was done. From the data and codes, categories were generated. Finally, a core category was constructed explaining the process of maintaining work life when living with IBS. Results Balancing work life while being under threat of symptoms constituted of four categories, being prepared, restricting impact, reconciling and adjusting. Persons with IBS restricted the impact of IBS on work by using strategies and upholding daily routines and strived to being prepared by exerting control over work life. These ongoing processes served to limit the influence of IBS on work by symptoms being less intense, perceived as less frequent, or not as bothersome. Reconciling IBS with work life was understood as a successful outcome from being prepared and restricting impact but was also influenced by the individual’s outlook on life. Adjusting to other people at work interfered with the strategies of being prepared, restricting impact, and reconciling, leaving persons with IBS more susceptible to symptoms. Conclusions This study deepens the understanding of the work situation for persons with IBS. Health care professionals can use the results of this study in the dialogue with the patient discussing work ability and sick leave. The results imply that although balancing work life under threat of symptoms can be a struggle, there are strategies that persons with IBS and employers together can initiate and use to reduce impact on work on several different levels.
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Matisz C, Gruber A. Neuroinflammatory remodeling of the anterior cingulate cortex as a key driver of mood disorders in gastrointestinal disease and disorders. Neurosci Biobehav Rev 2022; 133:104497. [DOI: 10.1016/j.neubiorev.2021.12.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 11/10/2021] [Accepted: 12/09/2021] [Indexed: 02/08/2023]
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Hillestad EMR, van der Meeren A, Nagaraja BH, Bjørsvik BR, Haleem N, Benitez-Paez A, Sanz Y, Hausken T, Lied GA, Lundervold A, Berentsen B. Gut bless you: The microbiota-gut-brain axis in irritable bowel syndrome. World J Gastroenterol 2022; 28:412-431. [PMID: 35125827 PMCID: PMC8790555 DOI: 10.3748/wjg.v28.i4.412] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 06/24/2021] [Accepted: 01/13/2022] [Indexed: 12/16/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal symptoms, recently described as a disturbance of the microbiota-gut-brain axis. Despite decades of research, the pathophysiology of this highly heterogeneous disorder remains elusive. However, a dramatic change in the understanding of the underlying pathophysiological mechanisms surfaced when the importance of gut microbiota protruded the scientific picture. Are we getting any closer to understanding IBS' etiology, or are we drowning in unspecific, conflicting data because we possess limited tools to unravel the cluster of secrets our gut microbiota is concealing? In this comprehensive review we are discussing some of the major important features of IBS and their interaction with gut microbiota, clinical microbiota-altering treatment such as the low FODMAP diet and fecal microbiota transplantation, neuroimaging and methods in microbiota analyses, and current and future challenges with big data analysis in IBS.
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Affiliation(s)
- Eline Margrete Randulff Hillestad
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Aina van der Meeren
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Bharat Halandur Nagaraja
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Ben René Bjørsvik
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Noman Haleem
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
| | - Alfonso Benitez-Paez
- Host-Microbe Interactions in Metabolic Health Laboratory, Principe Felipe Research Center, Valencia 46012, Spain
| | - Yolanda Sanz
- Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council, Paterna-Valencia 46980, Spain
| | - Trygve Hausken
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
| | - Gülen Arslan Lied
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
- Center for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
| | - Arvid Lundervold
- Mohn Medical Imaging and Visualization Center, Department of Radiology, Haukeland University Hospital, Bergen 5021, Norway
- Department of Biomedicine, University of Bergen, Bergen 5021, Norway
| | - Birgitte Berentsen
- Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway
- National Center for Functional Gastrointestinal Disorders, Department of Medicine, Haukeland University Hospital, Bergen 5021, Norway
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Fecal Microbiota Signatures Are Not Consistently Related to Symptom Severity in Irritable Bowel Syndrome. Dig Dis Sci 2022; 67:5137-5148. [PMID: 35624331 PMCID: PMC9587953 DOI: 10.1007/s10620-022-07543-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 03/01/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is the most prevalent functional bowel disorder, but its pathophysiology is still unknown. Although a microbial signature associated with IBS severity has been suggested, its association with IBS severity still remains largely unknown. AIMS This study aims to assess longitudinal dynamics of fecal microbiota and short-chain fatty acids (SCFAs) in different IBS severity groups and study the association with stool pattern, diet, depression, anxiety, and quality of life (QoL). METHODS A longitudinal study was performed, including n = 91 IBS patients and n = 28 matched controls. All participants collected fecal samples for microbiota composition and SCFA analysis and completed validated questionnaires regarding IBS severity, stool pattern, depression, anxiety, and IBS-QoL at two timepoints with four weeks in-between. Diet was assessed at the first timepoint. RESULTS Over time, 36% of IBS patients changed in severity group, and 53% changed in predominant stool pattern. The largest proportion of microbiota variation was explained by the individual (R2 = 70.07%). Microbiota alpha diversity and composition, and SCFAs did not differ between IBS severity groups, nor between IBS and controls. Relative abundances of Bifidobacterium, Terrisporobacter, and Turicibacter consistently differed between IBS and controls, but not between IBS severity groups. Large dynamics over time were observed in the association of microbiota composition with questionnaire data where IBS symptom severity was associated at T1 but not at T2. CONCLUSIONS Fecal microbiota and SCFA signatures were not consistently associated with IBS severity over time, indicating the importance of repeated sampling in IBS research.
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de Lima AMDL, de Lima Rosa G, Müller Guzzo EF, Padilha RB, Costa da Silva R, Silveira AK, de Lima Morales D, Conci de Araujo M, Fonseca Moreira JC, Barth AL, Coitinho AS, Van Der Sand ST. Gut microbiota modulation by prednisolone in a rat kindling model of pentylenetetrazol (PTZ)-induced seizure. Microb Pathog 2021; 163:105376. [PMID: 34974121 DOI: 10.1016/j.micpath.2021.105376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/02/2021] [Accepted: 12/28/2021] [Indexed: 11/26/2022]
Abstract
The gut microbiota is a complex community composed by several microorganisms that interact in the maintenance of homeostasis and contribute to physiological processes, including brain function. The relationship of the taxonomic composition of the gut microbiota with neurological diseases such as autism, Parkinson's, Alzheimer's, anxiety, and depression is widely recognized. The immune system is an important intermediary between the gut microbiota and the central nervous system, being one of the communication routes of the gut-brain axis. Although the complexity of the relationship between inflammation and epilepsy has not yet been elucidated, inflammatory processes are similar in many ways to the consequences of dysbiosis and contribute to disease progression. This study aimed to analyze the taxonomic composition of the gut microbiota of rats treated with prednisolone in a kindling model of epilepsy. Male Wistar rats (90 days, n = 24) divided into four experimental groups: sodium chloride solution 0.9 g%, diazepam 2 mg/kg, prednisolone 1 mg/kg, and prednisolone 5 mg/kg administered intraperitoneally (i.p.) for 14 days. The kindling model was induced by pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. The taxonomic profile was established by applying metagenomic DNA sequencing. There was no change in alpha diversity, and the composition of the gut microbiota between prednisolone and diazepam was similar. The significant increase in Verrucomicrobia, Saccharibacteria, and Actinobacteria may be related to the protective activity against seizures and inflammatory processes that cause some cases of epilepsy. Further studies are needed to investigate the functional influence that these species have on epilepsy and the inflammatory processes that trigger it.
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Affiliation(s)
- Amanda Muliterno Domingues Lourenço de Lima
- Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil
| | - Gabriel de Lima Rosa
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil
| | - Edson Fernando Müller Guzzo
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil
| | - Rafael Bremm Padilha
- Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil
| | - Rodrigo Costa da Silva
- Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil
| | - Alexandre Kleber Silveira
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2.600 - Annex, Porto Alegre, RS, Brazil
| | - Daiana de Lima Morales
- Laboratório de Pesquisa em Resistência Bacteriana, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2.350, Porto Alegre, RS, Brazil
| | - Milena Conci de Araujo
- Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil
| | - José Claudio Fonseca Moreira
- Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Ramiro Barcelos 2.600 - Annex, Porto Alegre, RS, Brazil
| | - Afonso Luís Barth
- Laboratório de Pesquisa em Resistência Bacteriana, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2.350, Porto Alegre, RS, Brazil
| | - Adriana Simon Coitinho
- Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil.
| | - Sueli Teresinha Van Der Sand
- Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Rua Sarmento Leite 500, Porto Alegre, RS, Brazil
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Neier K, Grant TE, Palmer RL, Chappell D, Hakam SM, Yasui KM, Rolston M, Settles ML, Hunter SS, Madany A, Ashwood P, Durbin-Johnson B, LaSalle JM, Yasui DH. Sex disparate gut microbiome and metabolome perturbations precede disease progression in a mouse model of Rett syndrome. Commun Biol 2021; 4:1408. [PMID: 34916612 PMCID: PMC8677842 DOI: 10.1038/s42003-021-02915-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 11/11/2021] [Indexed: 12/24/2022] Open
Abstract
Rett syndrome (RTT) is a regressive neurodevelopmental disorder in girls, characterized by multisystem complications including gut dysbiosis and altered metabolism. While RTT is known to be caused by mutations in the X-linked gene MECP2, the intermediate molecular pathways of progressive disease phenotypes are unknown. Mecp2 deficient rodents used to model RTT pathophysiology in most prior studies have been male. Thus, we utilized a patient-relevant mouse model of RTT to longitudinally profile the gut microbiome and metabolome across disease progression in both sexes. Fecal metabolites were altered in Mecp2e1 mutant females before onset of neuromotor phenotypes and correlated with lipid deficiencies in brain, results not observed in males. Females also displayed altered gut microbial communities and an inflammatory profile that were more consistent with RTT patients than males. These findings identify new molecular pathways of RTT disease progression and demonstrate the relevance of further study in female Mecp2 animal models.
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Affiliation(s)
- Kari Neier
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | - Tianna E Grant
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | - Rebecca L Palmer
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | - Demario Chappell
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | - Sophia M Hakam
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | | | - Matt Rolston
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | | | | | - Abdullah Madany
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | - Paul Ashwood
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
| | - Blythe Durbin-Johnson
- UC Davis Genome Center, Davis, CA, USA
- UC Davis School of Medicine, Department of Public Health Sciences, Davis, CA, USA
| | - Janine M LaSalle
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA.
- UC Davis Genome Center, Davis, CA, USA.
| | - Dag H Yasui
- UC Davis School of Medicine, Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, Davis, CA, USA
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Labus JS, Mayer EA, Tillisch K, Aagaard KM, Stains J, Broniowska K, Van Remortel C, Tun G, Rapkin A. Dysregulation in Sphingolipid Signaling Pathways is Associated With Symptoms and Functional Connectivity of Pain Processing Brain Regions in Provoked Vestibulodynia. THE JOURNAL OF PAIN 2021; 22:1586-1605. [PMID: 34029688 PMCID: PMC10460622 DOI: 10.1016/j.jpain.2021.04.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 03/27/2021] [Accepted: 04/29/2021] [Indexed: 10/21/2022]
Abstract
Provoked vestibulodynia (PVD) is a chronic pain disorder characterized by local hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Despite decades of study, the lack of identified biomarkers has slowed the development of effective therapies. The primary aim of this study was to use metabolomics to identify novel biochemical mechanisms in vagina and blood underlying brain biomarkers and symptoms in PVD, thereby closing this knowledge gap. Using a cross-sectional case-control observational study design, untargeted and unbiased metabolomic profiling of vaginal fluid and plasma was performed in women with PVD compared to healthy controls. In women with PVD, we also obtained assessments of vulvar pain, vestibular and vaginal muscle tenderness, and 24-hour symptom intensity alongside resting-state brain functional connectivity of brain regions involved in pain processing and modulation. Compared to healthy controls, women with PVD demonstrated differences primarily in vaginal (but not plasma) concentrations of metabolites of the sphingolipid signaling pathways, suggesting localized effects in vagina and vulvar vestibule rather than systemic effects. Our findings reveal that dysregulation of sphingolipid metabolism in PVD is associated with increased vulvar pain and muscle tenderness, sexual dysfunction, and decreased functional connectivity strength in pain processing/modulatory brain regions. This data collectively suggests that alterations in sphingolipid signaling pathways are likely an important molecular biomarker in PVD that could lead to new targets for therapeutic intervention. PERSPECTIVE: This manuscript presents the results of a robust, unbiased molecular assessment of plasma and vaginal fluid samples in women with provoked vestibulodynia compared to healthy controls. The findings suggest that alterations in sphingolipid signaling pathways are associated with symptoms and brain biomarkers and may be an important molecular marker that could provide new targets for therapeutic intervention.
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Affiliation(s)
- Jennifer S Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California; Brain Research Institute UCLA, Gonda (Goldschmied) Neuroscience and Genetics Research Center, Los Angeles, California.
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
| | - Kirsten Tillisch
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
| | - Kjersti M Aagaard
- Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas; Department of Molecular and Human Genetics, Bioinformatics Research Laboratory, Baylor College of Medicine, Houston, Texas; Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas
| | - Jean Stains
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
| | | | - Charlotte Van Remortel
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
| | - Guistinna Tun
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
| | - Andrea Rapkin
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California; Department of Obstetrics and Gynecology, David Geffen School of Medicine at the University of California, Los Angeles, California
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Wang JK, Yan B, Zhao JM, Yuan LP. Effect of gut microbiota from Henoch-Schönlein Purpura patients on acid-sensitive ion channel 3 expression and intestinal motility in germ-free rats. BMC Pediatr 2021; 21:536. [PMID: 34852816 PMCID: PMC8638173 DOI: 10.1186/s12887-021-03013-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 11/17/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND It has been proven that gut microbiota alterations are involved in the development of Henoch-Schönlein Purpura (HSP). However, the pathogenesis of HSP hasn't been eluciated. This study was to investigate the impact of gut microbiota from HSP on ASIC3 expression and interactions between microbiota and ASIC3 expression in the development of HSP. METHODS Feces collected from HSP and healthy children at the First Affiliated Hospital of Anhui Medical University were made into fecal microbial solutions. Germ-free rats were randomly assigned to either the control or HSP groups. The HSP group of rats were administered the fecal microbiota solution of HSP children, while the control group rats were administered the fecal microbiota solution of healthy children. Abdominal withdrawal reflex (AWR) and intestinal propulsion rate of the rats were used to determine visceral sensitivity. Composition of the gut microbiota of HSP children was determined using 16S rRNA gene sequencing. ASIC3 expression in the colon was ascertained through qRT-PCR as well as western blotting analysis. RESULTS The results showed a reduction in the number of species and abundance in the intestinal microbiota of children with HSP. Visceral sensitivity and intestinal propulsion rate of HSP group rats increased significantly, compared with the control group. Colon ASIC3 mRNA and protein levels in the HSP group were found to be upregulated. The microbiota dysbiosis of HSP patients could stimulate ASIC3 expression in the colon of Germ-free rats, which in turn affected intestinal motility. CONCLUSIONS These results suggested that HSP children had intestinal microbiota disorder, which might affect gut motility by down-regulating colon ASIC3 expression in rats.
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Affiliation(s)
- Jin-Kun Wang
- Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Bo Yan
- Department of Medical Technology, Anhui Medical College, Hefei, 230026, China
| | - Jun-Mei Zhao
- Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Li-Ping Yuan
- Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
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Jacobs JP, Gupta A, Bhatt RR, Brawer J, Gao K, Tillisch K, Lagishetty V, Firth R, Gudleski GD, Ellingson BM, Labus JS, Naliboff BD, Lackner JM, Mayer EA. Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement. MICROBIOME 2021; 9:236. [PMID: 34847963 PMCID: PMC8630837 DOI: 10.1186/s40168-021-01188-6] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 11/04/2021] [Indexed: 05/07/2023]
Abstract
BACKGROUND There is growing recognition that bidirectional signaling between the digestive tract and the brain contributes to irritable bowel syndrome (IBS). We recently showed in a large randomized controlled trial that cognitive behavioral therapy (CBT) reduces IBS symptom severity. This study investigated whether baseline brain and gut microbiome parameters predict CBT response and whether response is associated with changes in the brain-gut-microbiome (BGM) axis. METHODS Eighty-four Rome III-diagnosed IBS patients receiving CBT were drawn from the Irritable Bowel Syndrome Outcome Study (IBSOS; ClinicalTrials.gov NCT00738920) for multimodal brain imaging and psychological assessments at baseline and after study completion. Fecal samples were collected at baseline and post-treatment from 34 CBT recipients for 16S rRNA gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acids. Clinical measures, brain functional connectivity and microstructure, and microbiome features associated with CBT response were identified by multivariate linear and negative binomial models. RESULTS At baseline, CBT responders had increased fecal serotonin levels, and increased Clostridiales and decreased Bacteroides compared to non-responders. A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy (AUROC 0.96). Following treatment, CBT responders demonstrated reduced functional connectivity in regions of the sensorimotor, brainstem, salience, and default mode networks and changes in white matter in the basal ganglia and other structures. Brain changes correlated with microbiome shifts including Bacteroides expansion in responders. CONCLUSIONS Pre-treatment intestinal microbiota and serotonin levels were associated with CBT response, suggesting that peripheral signals from the microbiota can modulate central processes affected by CBT that generate abdominal symptoms in IBS. CBT response is characterized by co-correlated shifts in brain networks and gut microbiome that may reflect top-down effects of the brain on the microbiome during CBT. Video abstract.
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Affiliation(s)
- Jonathan P Jacobs
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Arpana Gupta
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
| | - Ravi R Bhatt
- Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine at USC, University of Southern California, Los Angeles, USA
| | - Jacob Brawer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
| | - Kan Gao
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
| | - Kirsten Tillisch
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
| | - Venu Lagishetty
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA
| | - Rebecca Firth
- Division of Behavioral Medicine, Jacobs School of Medicine, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Gregory D Gudleski
- Division of Behavioral Medicine, Jacobs School of Medicine, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Benjamin M Ellingson
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Department of Radiological Sciences, UCLA, Los Angeles, CA, USA
- Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA
| | - Jennifer S Labus
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
| | - Bruce D Naliboff
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA
| | - Jeffrey M Lackner
- Division of Behavioral Medicine, Jacobs School of Medicine, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Emeran A Mayer
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA, Los Angeles, CA, USA.
- David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA, Los Angeles, CA, USA.
- G. Oppenheimer Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Division of Digestive Diseases, David School of Medicine at UCLA, CHS 42-210 MC737818, 10833 Le Conte Avenue, Los Angeles, USA.
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Leclercq S, Schwarz M, Delzenne NM, Stärkel P, de Timary P. Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms. Transl Psychiatry 2021; 11:503. [PMID: 34599147 PMCID: PMC8486842 DOI: 10.1038/s41398-021-01610-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 08/11/2021] [Accepted: 08/20/2021] [Indexed: 02/06/2023] Open
Abstract
The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which remained poorly explored in patients with alcohol use disorder (AUD). The metabolites arising from the tryptophan-kynurenine pathway have gained considerable attention since they are at the interface between intestinal bacteria, host immune response and brain functions. This study described the circulating levels of kynurenine metabolites in AUD patients, at the onset (T1) and end (T2) of a 3-week detoxification program, and tested correlations between those metabolites and inflammatory markers, the gut microbiota and the psychological symptoms. Increased concentration of the neurotoxic metabolite quinolinic acid (QUIN) and decreased levels of the neuroprotector metabolite kynurenic acid (KYNA) which both modulate glutamatergic neurotransmission were observed in AUD patients, particularly at T2. The inflammatory marker hsCRP was associated with several metabolic ratios of the kynurenine pathway. Tryptophan, KYNA and QUIN were correlated with depression, alcohol craving and reaction time, respectively. Analysis of gut microbiota revealed that bacteria known as short-chain fatty acid producers, as well as bacterial metabolites including butyrate and medium-chain fatty acids were associated with some metabolites of the tryptophan-kynurenine pathway. Targeting the glutamatergic neurotransmission through the modulation of the kynurenine pathway, by manipulating the gut microbiota, might represent an interesting alternative for modulating alcohol-related behavior.
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Affiliation(s)
- Sophie Leclercq
- grid.7942.80000 0001 2294 713XInstitute of Neuroscience, Université catholique de Louvain (UCLouvain), Brussels, Belgium ,grid.7942.80000 0001 2294 713XMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Markus Schwarz
- grid.411095.80000 0004 0477 2585Institute of Laboratory Medicine, LMU Klinikum Munich, Munich, Germany
| | - Nathalie M. Delzenne
- grid.7942.80000 0001 2294 713XMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Peter Stärkel
- grid.7942.80000 0001 2294 713XLaboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, Université catholique de Louvain (UCLouvain), Brussels, Belgium ,grid.48769.340000 0004 0461 6320Department of Hepatogastroenterology, Cliniques universitaires Saint-Luc, Brussels, Belgium
| | - Philippe de Timary
- Institute of Neuroscience, Université catholique de Louvain (UCLouvain), Brussels, Belgium. .,Department of Adult Psychiatry, Cliniques universitaires Saint-Luc, Brussels, Belgium.
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Ferrier L, Eutamène H, Siegwald L, Marquard AM, Tondereau V, Chevalier J, Jacot GE, Favre L, Theodorou V, Vicario M, Rytz A, Bergonzelli G, Garcia-Rodenas CL. Human milk oligosaccharides alleviate stress-induced visceral hypersensitivity and associated microbiota dysbiosis. J Nutr Biochem 2021; 99:108865. [PMID: 34582967 DOI: 10.1016/j.jnutbio.2021.108865] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 06/11/2021] [Accepted: 09/01/2021] [Indexed: 02/08/2023]
Abstract
Pain-related functional gastrointestinal disorders (FGIDs) are characterized by visceral hypersensitivity (VHS) associated with alterations in the microbiota-gut-brain axis. Since human milk oligosaccharides (HMOs) modulate microbiota, gut and brain, we investigated whether HMOs impact VHS, and explored the role of gut microbiota. To induce VHS, C57BL/6JRj mice received hourly water avoidance stress (WAS) sessions for 10 d, or antibiotics (ATB) for 12 d. Challenged and unchallenged (Sham) animals were fed AIN93M diet (Cont) or AIN93M containing 1% of a 6-HMO mix (HMO6). VHS was assessed by monitoring the visceromotor response to colorectal distension. Fecal microbiome was analyzed by shotgun metagenomics. The effect of HMO6 sub-blends on VHS and nociceptive pathways was further tested using the WAS model. In mice fed Cont, WAS and ATB increased the visceromotor response to distension. HMO6 decreased WAS-mediated electromyographic rise at most distension volumes and overall Area Under Curve (AUC=6.12±0.50 in WAS/HMO6 vs. 9.46±0.50 in WAS/Cont; P<.0001). In contrast, VHS in ATB animals was not improved by HMO6. In WAS, HMO6 promoted most microbiota taxa and several functional pathways associated with low VHS and decreased those associated with high VHS. Among the sub-blends, 2'FL+DFL and LNT+6'SL reduced visceromotor response close to Sham/Cont values and modulated serotoninergic and CGRPα-related pathways. This research further substantiates the capacity of HMOs to modulate the microbiota-gut-brain communication and identifies mitigation of abdominal pain as a new HMO benefit. Ultimately, our findings suggest the value of specific HMO blends to alleviate pain associated FGIDs such as infantile colic or Irritable Bowel Syndrome.
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Affiliation(s)
- Laurent Ferrier
- Nestlé Institute of Health Sciences, Nestle Research, Lausanne, Switzerland
| | - Hélène Eutamène
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Léa Siegwald
- Nestlé Institute of Health Sciences, Nestle Research, Lausanne, Switzerland
| | | | - Valerie Tondereau
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Julien Chevalier
- Nestlé Institute of Health Sciences, Nestle Research, Lausanne, Switzerland
| | - Guillaume E Jacot
- Nestlé Institute of Health Sciences, Nestle Research, Lausanne, Switzerland
| | - Laurent Favre
- Project Management, Nestle Research, Lausanne, Switzerland
| | - Vassilia Theodorou
- Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France
| | - Maria Vicario
- Nestlé Institute of Health Sciences, Nestle Research, Lausanne, Switzerland
| | - Andreas Rytz
- Clinical Research Unit, Nestle Research, Lausanne, Switzerland
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Ma J, Wu JJ, Hua XY, Zheng MX, Huo BB, Xing XX, Feng SY, Li B, Xu J. Alterations in brain structure and function in patients with osteonecrosis of the femoral head: a multimodal MRI study. PeerJ 2021; 9:e11759. [PMID: 34484979 PMCID: PMC8381875 DOI: 10.7717/peerj.11759] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 06/21/2021] [Indexed: 11/30/2022] Open
Abstract
Background Pain, a major symptom of osteonecrosis of the femoral head (ONFH), is a complex sensory and emotional experience that presents therapeutic challenges. Pain can cause neuroplastic changes at the cortical level, leading to central sensitization and difficulties with curative treatments; however, whether changes in structural and functional plasticity occur in patients with ONFH remains unclear. Methods A total of 23 ONFH inpatients who did not undergo surgery (14 males, nine females; aged 55.61 ± 13.79 years) and 20 controls (12 males, eight females; aged 47.25 ± 19.35 years) were enrolled. Functional indices of the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and a structural index of tract-based spatial statistics (TBSS) were calculated for each participant. The probability distribution of fiber direction was determined according to the ALFF results. Results ONFH patients demonstrated increased ALFF in the bilateral dorsolateral superior frontal gyrus, right medial superior frontal gyrus, right middle frontal gyrus, and right supplementary motor area. In contrast, ONFH patients showed decreased ReHo in the left superior parietal gyrus and right inferior temporal gyrus. There were no significant differences in TBSS or probabilistic tractography. Conclusion These results indicate cerebral pain processing in ONFH patients. It is advantageous to use functional magnetic resonance imaging to better understand pain pathogenesis and identify new therapeutic targets in ONFH patients.
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Affiliation(s)
- Jie Ma
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jia-Jia Wu
- Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xu-Yun Hua
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University, Shanghai, China.,Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Mou-Xiong Zheng
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Bei-Bei Huo
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiang-Xin Xing
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Sheng-Yi Feng
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Bo Li
- Department of Traumatology and Orthopedics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jianguang Xu
- School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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48
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Bonaz B, Lane RD, Oshinsky ML, Kenny PJ, Sinha R, Mayer EA, Critchley HD. Diseases, Disorders, and Comorbidities of Interoception. Trends Neurosci 2021; 44:39-51. [PMID: 33378656 DOI: 10.1016/j.tins.2020.09.009] [Citation(s) in RCA: 134] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 09/21/2020] [Accepted: 09/25/2020] [Indexed: 12/17/2022]
Abstract
Interoception, the sense of the body's internal physiological state, underpins homeostatic reflexes, motivational states, and sensations contributing to emotional experiences. The continuous nature of interoceptive processing, coupled to behavior, is implicated in the neurobiological construction of the sense of self. Aberrant integration and control of interoceptive signals, originating in the brain and/or the periphery, can perturb the whole system. Interoceptive abnormalities are implicated in the pathophysiology of psychiatric disorders and in the symptomatic expression of developmental, neurodegenerative, and neurological disorders. Moreover, interoceptive mechanisms appear central to somatic disorders of brain-body interactions, including functional digestive disorders, chronic pain, and comorbid conditions. The present article provides an overview of disorders of interoception and suggests future directions for better understanding, diagnosis, and management of these disorders.
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Affiliation(s)
- Bruno Bonaz
- Université Grenoble Alpes, Inserm, U1216, Grenoble Institute Neurosciences and Division of Hepato-Gastroenterology, CHU Grenoble Alpes, 38000 Grenoble, France.
| | - Richard D Lane
- Department of Psychiatry, University of Arizona, Tucson, AZ 85724-5002, USA; Department of Psychology, University of Arizona, Tucson, AZ 85724-5002, USA; Department of Neuroscience, University of Arizona, Tucson, AZ 85724-5002, USA
| | - Michael L Oshinsky
- National Institute of Neurological Disorders and Stroke/National Institutes of Health, Bethesda, MD 20894, USA
| | - Paul J Kenny
- Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Rajita Sinha
- Yale Stress Center, Yale School of Medicine, New Haven, CT, 06519, USA
| | - Emeran A Mayer
- G. Oppenheimer Family Center for Neurobiology of Stress and Resilience, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Hugo D Critchley
- Department of Neuroscience, Brighton and Sussex Medical School, Brighton, UK
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West C, McVey Neufeld KA. Animal models of visceral pain and the role of the microbiome. NEUROBIOLOGY OF PAIN (CAMBRIDGE, MASS.) 2021; 10:100064. [PMID: 34151049 PMCID: PMC8190503 DOI: 10.1016/j.ynpai.2021.100064] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 05/16/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023]
Abstract
Visceral pain refers to pain arising from the internal organs and is distinctly different from the expression and mechanisms of somatic pain. Diseases and disorders with increased visceral pain are associated with significantly reduced quality of life and incur large financial costs due to medical visits and lost work productivity. In spite of the notable burden of illness associated with those disorders involving increased visceral pain, and some knowledge regarding etiology, few successful therapeutics have emerged, and thus increased attention to animal models of visceral hypersensitivity is warranted in order to elucidate new treatment opportunities. Altered microbiota-gut-brain (MGB) axis communication is central to the comorbid gastrointestinal/psychiatric diseases of which increased visceral (intestinal) sensitivity is a hallmark. This has led to a particular focus on intestinal microbiome disruption and its potential role in the etiology of heightened visceral pain. Here we provide a review of studies examining models of heightened visceral pain due to altered bidirectional communication of the MGB axis, many of which are conducted on a background of stress exposure. We discuss work in which the intestinal microbiota has either been directly manipulated (as with germ-free, antibiotic, and fecal microbial transplantation studies) or indirectly affected through early life or adult stress, inflammation, and infection. Animal models of visceral pain alterations with accompanying changes to the intestinal microbiome have the highest face and construct validity to the human condition and are the focus of the current review.
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Affiliation(s)
- Christine West
- McMaster Brain-Body Institute at St Joseph’s Healthcare, Hamilton, Ontario, Canada
| | - Karen-Anne McVey Neufeld
- McMaster Brain-Body Institute at St Joseph’s Healthcare, Hamilton, Ontario, Canada
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
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Gros M, Gros B, Mesonero JE, Latorre E. Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management. J Clin Med 2021; 10:jcm10153429. [PMID: 34362210 PMCID: PMC8347293 DOI: 10.3390/jcm10153429] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/13/2021] [Accepted: 07/28/2021] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose aetiology is still unknown. Most hypotheses point out the gut-brain axis as a key factor for IBS. The axis is composed of different anatomic and functional structures intercommunicated through neurotransmitters. However, the implications of key neurotransmitters such as norepinephrine, serotonin, glutamate, GABA or acetylcholine in IBS are poorly studied. The aim of this review is to evaluate the current evidence about neurotransmitter dysfunction in IBS and explore the potential therapeutic approaches. IBS patients with altered colorectal motility show augmented norepinephrine and acetylcholine levels in plasma and an increased sensitivity of central serotonin receptors. A decrease of colonic mucosal serotonin transporter and a downregulation of α2 adrenoceptors are also correlated with visceral hypersensitivity and an increase of 5-hydroxyindole acetic acid levels, enhanced expression of high affinity choline transporter and lower levels of GABA. Given these neurotransmitter dysfunctions, novel pharmacological approaches such as 5-HT3 receptor antagonists and 5-HT4 receptor agonists are being explored for IBS management, for their antiemetic and prokinetic effects. GABA-analogous medications are being considered to reduce visceral pain. Moreover, agonists and antagonists of muscarinic receptors are under clinical trials. Targeting neurotransmitter dysfunction could provide promising new approaches for IBS management.
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Affiliation(s)
- Mónica Gros
- Centro de Salud Univérsitas, Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain;
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain; (B.G.); (J.E.M.)
| | - Belén Gros
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain; (B.G.); (J.E.M.)
- Servicio de Urgencias, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
| | - José Emilio Mesonero
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain; (B.G.); (J.E.M.)
- Departamento de Farmacología, Fisiología y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50009 Zaragoza, Spain
- Instituto Agroalimentario de Aragón—IA2—(Universidad de Zaragoza—CITA), 50013 Zaragoza, Spain
| | - Eva Latorre
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain; (B.G.); (J.E.M.)
- Instituto Agroalimentario de Aragón—IA2—(Universidad de Zaragoza—CITA), 50013 Zaragoza, Spain
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain
- Correspondence:
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