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Yang XY, Wang HQ, Wang ZZ, Chen NH. Linking depression and neuroinflammation: Crosstalk between glial cells. Eur J Pharmacol 2025; 995:177408. [PMID: 39984011 DOI: 10.1016/j.ejphar.2025.177408] [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: 11/11/2024] [Revised: 02/09/2025] [Accepted: 02/19/2025] [Indexed: 02/23/2025]
Abstract
The inflammatory hypothesis is one of the more widely accepted pathogenesis of depression. Glia plays an important immunomodulatory role in neuroinflammation, mediating interactions between the immune system and the central nervous system (CNS). Glial cell-driven neuroinflammation is not only an important pathological change in depression, but also a potential therapeutic target. This review discusses the association between depression and glial cell-induced neuroinflammation and elucidates the role of glial cell crosstalk in neuroinflammation. Firstly, we focus on the role of glial cells in neuroinflammation in depression and glial cell interactions; secondly, we categorize changes in different glial cells in animal models of depression and depressed patients, focusing on how glial cells mediate inflammatory responses and exacerbate depressive symptoms; Thirdly, we review how conventional and novel antidepressants affect the phenotype and function of glial cells, thereby exerting anti-inflammatory activity; finally, we discuss the role of the gut-brain axis in glial cell function and depression, and objectively analyze the problems that remain in current antidepressant therapy. This review aims to provide an objective analysis of how glial cell cross-talk may mediate neuroinflammation and thereby influence pathologic progression of depression. It is concluded that a novel therapeutic strategy may be to ameliorate glial cell-mediated inflammatory responses.
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Affiliation(s)
- Xue-Ying Yang
- Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Hui-Qin Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; School of Pharmacy, Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha, 410208, Hunan, China
| | - Zhen-Zhen Wang
- State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Nai-Hong Chen
- Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; School of Pharmacy, Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha, 410208, Hunan, China.
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2
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Zhang C, Chen Y, Duan R, Zhang Y, Zheng H, Zhang J, Zhang T, Xu J, Li K, Pei F, Duan L. Preconception maternal gut dysbiosis affects enteric nervous system development and disease susceptibility in offspring via the GPR41-GDNF/RET/SOX10 signaling pathway. IMETA 2025; 4:e70012. [PMID: 40236770 PMCID: PMC11995169 DOI: 10.1002/imt2.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 02/22/2025] [Accepted: 02/27/2025] [Indexed: 04/17/2025]
Abstract
Maternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how gut microbiota alterations during the preconception period influence the offspring remains limited. In this study, we investigated the impact and mechanisms of preconception maternal gut dysbiosis on the development of the enteric nervous system (ENS) in mice. We found that preconception maternal exposure to antibiotics led to the abnormal development of the ENS in offspring, increasing their susceptibility to water avoidance stress at the adult stage. Metagenomic, targeted metabolomic, and transcriptomic analyses revealed that preconception antibiotic exposure disrupted the expression of genes crucial for embryonic ENS development by altering maternal gut microbiota composition. Multi-omics analysis combined with Limosilactobacillus reuteri and propionate gestational supplementation demonstrated that the maternal gut microbiota and metabolites may influence embryonic ENS development via the GPR41-GDNF/RET/SOX10 signaling pathway. Our findings highlight the critical importance of maintaining a healthy maternal gut microbiota before conception to support normal ENS development in offspring.
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Affiliation(s)
- Cunzheng Zhang
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Yuzhu Chen
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Ruqiao Duan
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Yiming Zhang
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Haonan Zheng
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Jindong Zhang
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Tao Zhang
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Jingxian Xu
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
| | - Kailong Li
- Department of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical SciencesPeking UniversityBeijingChina
| | - Fei Pei
- Department of PathologyPeking University Third HospitalBeijingChina
| | - Liping Duan
- Department of GastroenterologyPeking University Third HospitalBeijingChina
- Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal DiseasesBeijingChina
- PKUMed‐Wisbiom Joint Laboratory for Human Microbiome ResearchBeijingChina
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Liu M, Sheng Y, He Y, Wu S, Jin C, Shen L. Progresses in Questing for the Truth of Opioid-Related Constipation in Cancer Patients. J Cell Mol Med 2025; 29:e70553. [PMID: 40281681 PMCID: PMC12031673 DOI: 10.1111/jcmm.70553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 03/24/2025] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
Opioids are extensively utilised to manage pain in cancer patients, but may cause constipation which significantly impacts their prognosis and quality of life. Opioid-induced constipation (OIC) lacks effective drugs and management strategies. Opioids act on the enteric nervous system, intestinal barrier, intestinal immunity and intestinal microbiota, implying that OIC is a multifactorial process. This paper aims to examine the effects of opioids on the intestine, specifically the enteric nervous system, intestinal barrier and interstitial cells of Cajal (ICCs), and elucidate the primary mechanisms underlying OIC development and deterioration. This review suggests that enteric neurons, intestinal immunity and intestinal flora could serve as potential therapeutic targets for OIC.
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Affiliation(s)
- Mengxue Liu
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
| | - Yedong Sheng
- Nanjing University of Chinese MedicineNanjingJiangsuChina
| | - Yingrong He
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
| | - Shixiang Wu
- Nanjing University of Chinese MedicineNanjingJiangsuChina
| | - Chunhui Jin
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
| | - Lijuan Shen
- Wuxi Hospital Affiliated to Nanjing University of Chinese MedicineWuxiJiangsuChina
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Zhou M, Niu B, Ma J, Ge Y, Han Y, Wu W, Yue C. Intervention and research progress of gut microbiota-immune-nervous system in autism spectrum disorders among students. Front Microbiol 2025; 16:1535455. [PMID: 40143866 PMCID: PMC11936958 DOI: 10.3389/fmicb.2025.1535455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive and stereotyped behaviors, restricted interests, and sensory abnormalities. Its etiology is influenced by both genetic and environmental factors, with no definitive cause identified and no specific pharmacological treatments available, posing a significant burden on patients' families and society. In recent years, research has discovered that gut microbiota dysbiosis plays a crucial role in the pathogenesis of ASD. The gut microbiota can influence brain function and behavior through the gut-brain axis via the nervous system, immune system, and metabolic pathways. On the one hand, specific gut microbes such as Clostridium and Prevotella species are found to be abnormal in ASD patients, and their metabolic products, like short-chain fatty acids, serotonin, and GABA, are also involved in the pathological process of ASD. On the other hand, ASD patients exhibit immune system dysfunction, with gut immune cells and related cytokines affecting neural activities in the brain. Currently, intervention methods targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, have shown some potential in improving ASD symptoms. However, more studies are needed to explore their long-term effects and optimal treatment protocols. This paper reviews the mechanisms and interrelationships among gut microbiota, immune system, and nervous system in ASD and discusses the challenges and future directions of existing research, aiming to provide new insights for the prevention and treatment of ASD.
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Affiliation(s)
- Min Zhou
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medical Sciences, Yan’an University, Yan’an, China
| | - Baoming Niu
- School of Petroleum Engineering and Environmental Science, Yan’an University, Yan’an, China
| | - Jiarui Ma
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medical Sciences, Yan’an University, Yan’an, China
| | - Yukang Ge
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medical Sciences, Yan’an University, Yan’an, China
| | - Yanxin Han
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medical Sciences, Yan’an University, Yan’an, China
| | - Wenrui Wu
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medical Sciences, Yan’an University, Yan’an, China
| | - Changwu Yue
- Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medical Sciences, Yan’an University, Yan’an, China
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Arneth B. Gut-Brain Axis and Brain Microbiome Interactions from a Medical Perspective. Brain Sci 2025; 15:167. [PMID: 40002500 PMCID: PMC11853140 DOI: 10.3390/brainsci15020167] [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: 01/02/2025] [Revised: 02/03/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Background: The gut microbiome directly impacts brain health and activity, meaning the two are closely associated. This relationship suggests a link between microbial imbalances and diseases such as Alzheimer's, although multiple other contributing factors, such as genetics, also play a part. Additionally, recent studies discovered that cerebrospinal fluid has some microbial deoxyribonucleic acid (DNA), which can be interpreted to mean a microbiome exists in the brain too. The vagus nerve and the central nervous and immune systems are responsible for the connection between the brain and gut microbiome. Aims and Objectives: The main aim of this systematic review is to analyze existing research on the gut-brain axis and the brain microbiome to fill the current knowledge gap. Materials and Methods: A search was conducted on the PubMed database based on a set of predefined MeSH terms. Results: After the search, 2716 articles meeting the MeSH parameters were found in PubMed. This list was then downloaded and analyzed according to the inclusion/exclusion criteria, and 63 relevant papers were selected. Discussion: Bacteria in the gut microbiome produce some substances that are considered neuroactive. These compounds can directly or indirectly affect brain function through the gut-brain axis. However, various knowledge gaps on the mechanisms involved in this connection need to be addressed first.
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Affiliation(s)
- Borros Arneth
- Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, University Hospital of the University of Marburg UKGM, Philipps University Marburg, Baldingerstr., 35043 Marburg, Germany
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Silva D, Mendes FC, Stanzani V, Moreira R, Pinto M, Beltrão M, Sokhatska O, Severo M, Padrão P, Garcia-Larsen V, Delgado L, Moreira A, Moreira P. The Acute Effects of a Fast-Food Meal Versus a Mediterranean Food Meal on the Autonomic Nervous System, Lung Function, and Airway Inflammation: A Randomized Crossover Trial. Nutrients 2025; 17:614. [PMID: 40004945 PMCID: PMC11858349 DOI: 10.3390/nu17040614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/28/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES This study aimed to assess the acute effects of two isoenergetic but micronutrient-diverse meals-a Mediterranean-like meal (MdM) and a fast food-like meal (FFM)-on the autonomic nervous system (ANS), lung function, and airway inflammation response. METHODS Forty-six participants were enrolled in a randomized crossover clinical trial, consuming two isoenergetic meals: FFM (burger, fries, and sugar-sweetened drink) and MdM (vegetable soup, whole-wheat pasta, salad, olive oil, sardines, fruit, and water). Pupillometry assessed parasympathetic (MaxD, MinD, Con, ACV, MCV) and sympathetic (ADV, T75) nervous system outcomes. Lung function and airway inflammation were measured before and after each meal through spirometry and fractional exhaled nitric oxide (FeNO), respectively. RESULTS Mixed-effects model analysis showed that the MdM was associated with a hegemony of parasympathetic responses, with a significant increase of MaxD associated with a faster constriction velocity (ACV and MCV); on the other side, the FFM was associated with changes in the sympathetic response, showing a quicker redilation velocity (a decrease in T75). After adjusting for confounders, the mixed-effects models revealed that the FFM significantly decreased T75. Regarding lung function, a meal negatively impacted FVC (ae = -0.079, p < 0.001) and FEV1 (ae = -0.04, p = 0.017); however, FeNO increased, although after adjusting, no difference between meals was seen. CONCLUSIONS Our study showed that the FFM counteracted the parasympathetic activity of a meal, while a meal, irrespective of the type, decreased lung function and increased airway inflammation.
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Affiliation(s)
- Diana Silva
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
- Serviço de Imunoalergologia, Unidade Local de Saúde de São João, 4202-451 Porto, Portugal
- EPIUnit-Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; (M.S.); (P.P.); (P.M.)
| | - Francisca Castro Mendes
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
- EPIUnit-Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; (M.S.); (P.P.); (P.M.)
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
| | - Vânia Stanzani
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
| | - Rita Moreira
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
| | - Mariana Pinto
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
| | - Marília Beltrão
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
| | - Oksana Sokhatska
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
| | - Milton Severo
- EPIUnit-Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; (M.S.); (P.P.); (P.M.)
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
- School of Medicine and Biomedical Sciences, University of Porto, 4050-321 Porto, Portugal
| | - Patrícia Padrão
- EPIUnit-Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; (M.S.); (P.P.); (P.M.)
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
- Faculty of Nutrition and Food Sciences, University of Porto, 4150-180 Porto, Portugal
| | - Vanessa Garcia-Larsen
- Program in Human Nutrition, Department of International Health, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA;
| | - Luís Delgado
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
- Serviço de Imunoalergologia, Unidade Local de Saúde de São João, 4202-451 Porto, Portugal
- RISE-Health, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - André Moreira
- Basic and Clinical Immunology, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (F.C.M.); (V.S.); (R.M.); (M.P.); (M.B.); (O.S.); (L.D.); (A.M.)
- Serviço de Imunoalergologia, Unidade Local de Saúde de São João, 4202-451 Porto, Portugal
- EPIUnit-Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; (M.S.); (P.P.); (P.M.)
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
| | - Pedro Moreira
- EPIUnit-Institute of Public Health, University of Porto, 4050-600 Porto, Portugal; (M.S.); (P.P.); (P.M.)
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
- Faculty of Nutrition and Food Sciences, University of Porto, 4150-180 Porto, Portugal
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Degner KN, Bell JL, Jones SD, Won H. Just a SNP away: The future of in vivo massively parallel reporter assay. CELL INSIGHT 2025; 4:100214. [PMID: 39618480 PMCID: PMC11607654 DOI: 10.1016/j.cellin.2024.100214] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/03/2024] [Accepted: 10/06/2024] [Indexed: 04/03/2025]
Abstract
The human genome is largely noncoding, yet the field is still grasping to understand how noncoding variants impact transcription and contribute to disease etiology. The massively parallel reporter assay (MPRA) has been employed to characterize the function of noncoding variants at unprecedented scales, but its application has been largely limited by the in vitro context. The field will benefit from establishing a systemic platform to study noncoding variant function across multiple tissue types under physiologically relevant conditions. However, to date, MPRA has been applied to only a handful of in vivo conditions. Given the complexity of the central nervous system and its widespread interactions with all other organ systems, our understanding of neuropsychiatric disorder-associated noncoding variants would be greatly advanced by studying their functional impact in the intact brain. In this review, we discuss the importance, technical considerations, and future applications of implementing MPRA in the in vivo space with the focus on neuropsychiatric disorders.
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Affiliation(s)
- Katherine N. Degner
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jessica L. Bell
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Sean D. Jones
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Hyejung Won
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Xu X, Wei S, Lin M, Chen F, Zhang X, Zhu Y. The relationship between acrylamide and neurodegenerative diseases: gut microbiota as a new intermediate cue. Crit Rev Food Sci Nutr 2024:1-13. [PMID: 39668759 DOI: 10.1080/10408398.2024.2440602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
Acrylamide (AA), a compound formed during the thermal processing of high-carbohydrate foods, has been implicated in the onset and progression of neurodegenerative diseases. An increasing number of reports support that gut microbiota plays a significant role in brain function and diseases, suggesting it may act as a mediator between AA exposure and the development of neurodegenerative diseases. Available studies have shown that AA intake affects the composition of the gut microbiota and the integrity of the intestinal barrier, both of which are often thought to be associated with the pathogenesis of neurodegenerative diseases, given the numerous evidences linking gut microbiota with the brain. Based on the current understanding, this paper discusses that AA induces the onset and progression of neurodegenerative diseases by disrupting the composition of the gut microbiota and the structure of the intestinal barrier. Furthermore, it explores the interaction between probiotics and AA exposure, as well as the potential for polysaccharides and polyphenols to improve the gut microenvironment, which provides novel perspectives on modulating the neurodegenerative diseases caused by AA exposure through diet.
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Affiliation(s)
- Xinrui Xu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, P. R. China
| | - Siyu Wei
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, P. R. China
| | - Mengyi Lin
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, P. R. China
| | - Fang Chen
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, P. R. China
| | - Xin Zhang
- Department of Food Science and Engineering, Ningbo University, Ningbo, P. R. China
| | - Yuchen Zhu
- College of Food Science and Nutritional Engineering, National Engineering Research Centre for Fruits and Vegetables Processing, Key Laboratory of Storage and Processing of Fruits and Vegetables, Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education, China Agricultural University, Beijing, P. R. China
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9
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Pasupalak JK, Rajput P, Gupta GL. Gut microbiota and Alzheimer's disease: Exploring natural product intervention and the Gut-Brain axis for therapeutic strategies. Eur J Pharmacol 2024; 984:177022. [PMID: 39362390 DOI: 10.1016/j.ejphar.2024.177022] [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: 07/11/2024] [Revised: 09/14/2024] [Accepted: 09/30/2024] [Indexed: 10/05/2024]
Abstract
Numerous studies conducted over the last ten years have shown a strong correlation between the gut microbiota and the onset and progression of Alzheimer's disease (AD). However, the exact underlying mechanism is still unknown. An ongoing communication mechanism linking the gut and the brain is highlighted by the term "microbiota-gut-brain axis," which was originally coined the "gut-brain axis." Key metabolic, endocrine, neurological, and immunological mechanisms are involved in the microbiota‒gut‒brain axis and are essential for preserving brain homeostasis. Thus, the main emphasis of this review is how the gut microbiota contributes to the development of AD and how various natural products intervene in this disease. The first part of the review provides an outline of various pathways and relationships between the brain and gut microbiota, and the second part provides various mechanisms involved in the gut microbiota and AD. Finally, this review provides knowledge about natural products and their effectiveness in treating gut microbiota-induced AD. AD may be treated in the future by altering the gut microbiota with a customized diet, probiotics/prebiotics, plant products, and natural products. This entails altering the microbiological partners and products (such as amyloid protein) that these partners generate.
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Affiliation(s)
- Jajati K Pasupalak
- School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India
| | - Prabha Rajput
- School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India
| | - Girdhari Lal Gupta
- School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India.
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10
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Ma R, Li W, Peng Q, Ren A, Zhao L, Li J, Luo S. Association Between Gallstones and Depressive Symptoms: Results from NHANES and Mendelian Randomization Study. Psychol Res Behav Manag 2024; 17:3659-3676. [PMID: 39465037 PMCID: PMC11512777 DOI: 10.2147/prbm.s477449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/01/2024] [Indexed: 10/29/2024] Open
Abstract
Purpose Prior research has suggested a correlation between gallstones and depressive symptoms, yet the specifics of this relationship remain unclear. This study aims to explore the association between gallstones and depressive symptoms among adults. Patients and Methods Initially, we conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017 - March 2020. After propensity score matching (PSM) for participants with gallstones and those without gallstones, multivariate logistic regression analysis was used to explore the potential association between gallstones and depressive symptoms. This was followed by Mendelian randomization (MR) analysis to further elucidate the causal relationship between them. Using the genome-wide association study database, we extracted instrumental variables and performed bidirectional univariate and multivariate MR analyses. Results In the cross-sectional study of NHANES 2017 - March 2020, 835 pairs of participants with comparable characteristics, both with and without gallstones, were identified after PSM. The multivariate adjusted logistic regression analyses revealed a significant association between gallstones and depressive symptoms [fully adjusted model: OR=1.821 (95% CI, 1.181-2.808), P=0.007]. Subsequent MR analyses further clarified the causal relationship, indicating that genetically determined gallstones significantly increase the risk of developing depressive symptoms [forward univariate MR analysis: OR=1.04 (95% CI, 1.01-1.06), P=0.002; multivariate MR analysis: OR=1.03 (95% CI, 1.01-1.05), P=0.009], with no evidence of reverse causation [inverse univariate MR analysis: OR=1.28 (95% CI, 0.90-1.83), P=0.17]. Conclusion Gallstones are a risk factor for depressive symptoms among adults. Hence, we recommend timely depression screening for patients diagnosed with gallstones, facilitating early detection and effective treatment of depressive symptoms, thus alleviating its impact on both individuals and society.
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Affiliation(s)
- Ruidong Ma
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Wei Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Qiufeng Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Ao Ren
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Ling Zhao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Jiawei Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
| | - Shiqiao Luo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China
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11
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Van Hul M, Neyrinck AM, Everard A, Abot A, Bindels LB, Delzenne NM, Knauf C, Cani PD. Role of the intestinal microbiota in contributing to weight disorders and associated comorbidities. Clin Microbiol Rev 2024; 37:e0004523. [PMID: 38940505 PMCID: PMC11391702 DOI: 10.1128/cmr.00045-23] [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] [Indexed: 06/29/2024] Open
Abstract
SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.
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Affiliation(s)
- Matthias Van Hul
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, France/Belgium
| | - Audrey M Neyrinck
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
| | - Amandine Everard
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
| | | | - Laure B Bindels
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
| | - Nathalie M Delzenne
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
| | - Claude Knauf
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, France/Belgium
- INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), Université Paul Sabatier, Toulouse III, CHU Purpan, Toulouse, France
| | - Patrice D Cani
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, France/Belgium
- UCLouvain, Université catholique de Louvain, Institute of Experimental and Clinical Research (IREC), Brussels, Belgium
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12
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Lu S, Zhao Q, Guan Y, Sun Z, Li W, Guo S, Zhang A. The communication mechanism of the gut-brain axis and its effect on central nervous system diseases: A systematic review. Biomed Pharmacother 2024; 178:117207. [PMID: 39067168 DOI: 10.1016/j.biopha.2024.117207] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/15/2024] [Accepted: 07/23/2024] [Indexed: 07/30/2024] Open
Abstract
Gut microbiota is involved in intricate and active metabolic processes the host's brain function, especially its role in immune responses, secondary metabolism, and symbiotic connections with the host. Gut microbiota can promote the production of essential metabolites, neurotransmitters, and other neuroactive chemicals that affect the development and treatment of central nervous system diseases. This article introduces the relevant pathways and manners of the communication between the brain and gut, summarizes a comprehensive overview of the current research status of key gut microbiota metabolites that affect the functions of the nervous system, revealing those adverse factors that affect typical communication between the brain-gut axis, and outlining the efforts made by researchers to alleviate these neurological diseases through targeted microbial interventions. The relevant pathways and manners of communication between the brain and gut contribute to the experimental design of new treatment plans and drug development. The factors that may cause changes in gut microbiota and affect metabolites, as well as current intervention methods are summarized, which helps improve gut microbiota brain dialogue, prevent adverse triggering factors from interfering with the gut microbiota system, and minimize neuropathological changes.
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Affiliation(s)
- Shengwen Lu
- Department of Pharmaceutical Analysis, GAP Center, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China
| | - Qiqi Zhao
- Department of Pharmaceutical Analysis, GAP Center, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China
| | - Yu Guan
- Department of Pharmaceutical Analysis, GAP Center, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China
| | - Zhiwen Sun
- Department of Gastroenterology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China
| | - Wenhao Li
- School of Basic Medical Science of Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China
| | - Sifan Guo
- International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Xueyuan Road 3, Haikou 571199, China
| | - Aihua Zhang
- International Advanced Functional Omics Platform, Scientific Experiment Center, Hainan Medical University, Xueyuan Road 3, Haikou 571199, China; Graduate School, Heilongjiang University of Chinese Medicine, Harbin 150040, China; INTI International University, Nilai 71800, Malaysia.
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13
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He Y, Wang K, Su N, Yuan C, Zhang N, Hu X, Fu Y, Zhao F. Microbiota-gut-brain axis in health and neurological disease: Interactions between gut microbiota and the nervous system. J Cell Mol Med 2024; 28:e70099. [PMID: 39300699 PMCID: PMC11412916 DOI: 10.1111/jcmm.70099] [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: 04/18/2024] [Revised: 09/03/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024] Open
Abstract
Along with mounting evidence that gut microbiota and their metabolites migrate endogenously to distal organs, the 'gut-lung axis,' 'gut-brain axis,' 'gut-liver axis' and 'gut-renal axis' have been established. Multiple animal recent studies have demonstrated gut microbiota may also be a key susceptibility factor for neurological disorders such as Alzheimer's disease, Parkinson's disease and autism. The gastrointestinal tract is innervated by the extrinsic sympathetic and vagal nerves and the intrinsic enteric nervous system, and the gut microbiota interacts with the nervous system to maintain homeostatic balance in the host gut. A total of 1507 publications on the interactions between the gut microbiota, the gut-brain axis and neurological disorders are retrieved from the Web of Science to investigate the interactions between the gut microbiota and the nervous system and the underlying mechanisms involved in normal and disease states. We provide a comprehensive overview of the effects of the gut microbiota and its metabolites on nervous system function and neurotransmitter secretion, as well as alterations in the gut microbiota in neurological disorders, to provide a basis for the possibility of targeting the gut microbiota as a therapeutic agent for neurological disorders.
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Affiliation(s)
- Yuhong He
- Department of Operating RoomChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
- Department of Clinical Veterinary MedicineCollege of Veterinary Medicine, Jilin UniversityChangchunJilinChina
| | - Ke Wang
- Department of Operating RoomChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
| | - Niri Su
- Department of Clinical Veterinary MedicineCollege of Veterinary Medicine, Jilin UniversityChangchunJilinChina
| | - Chongshan Yuan
- Department of Clinical Veterinary MedicineCollege of Veterinary Medicine, Jilin UniversityChangchunJilinChina
| | - Naisheng Zhang
- Department of Clinical Veterinary MedicineCollege of Veterinary Medicine, Jilin UniversityChangchunJilinChina
| | - Xiaoyu Hu
- Department of Clinical Veterinary MedicineCollege of Veterinary Medicine, Jilin UniversityChangchunJilinChina
| | - Yunhe Fu
- Department of Clinical Veterinary MedicineCollege of Veterinary Medicine, Jilin UniversityChangchunJilinChina
| | - Feng Zhao
- Department of Operating RoomChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
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14
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Averina OV, Poluektova EU, Zorkina YA, Kovtun AS, Danilenko VN. Human Gut Microbiota for Diagnosis and Treatment of Depression. Int J Mol Sci 2024; 25:5782. [PMID: 38891970 PMCID: PMC11171505 DOI: 10.3390/ijms25115782] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 06/21/2024] Open
Abstract
Nowadays, depressive disorder is spreading rapidly all over the world. Therefore, attention to the studies of the pathogenesis of the disease in order to find novel ways of early diagnosis and treatment is increasing among the scientific and medical communities. Special attention is drawn to a biomarker and therapeutic strategy through the microbiota-gut-brain axis. It is known that the symbiotic interactions between the gut microbes and the host can affect mental health. The review analyzes the mechanisms and ways of action of the gut microbiota on the pathophysiology of depression. The possibility of using knowledge about the taxonomic composition and metabolic profile of the microbiota of patients with depression to select gene compositions (metagenomic signature) as biomarkers of the disease is evaluated. The use of in silico technologies (machine learning) for the diagnosis of depression based on the biomarkers of the gut microbiota is given. Alternative approaches to the treatment of depression are being considered by balancing the microbial composition through dietary modifications and the use of additives, namely probiotics, postbiotics (including vesicles) and prebiotics as psychobiotics, and fecal transplantation. The bacterium Faecalibacterium prausnitzii is under consideration as a promising new-generation probiotic and auxiliary diagnostic biomarker of depression. The analysis conducted in this review may be useful for clinical practice and pharmacology.
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Affiliation(s)
- Olga V. Averina
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
| | - Elena U. Poluektova
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
| | - Yana A. Zorkina
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
- V. Serbsky National Medical Research Centre of Psychiatry and Narcology, Kropotkinsky per. 23, 119034 Moscow, Russia
- Mental-Health Clinic No. 1 Named after N.A. Alekseev, Zagorodnoe Highway 2, 115191 Moscow, Russia
| | - Alexey S. Kovtun
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
| | - Valery N. Danilenko
- Vavilov Institute of General Genetics, Russian Academy of Sciences (RAS), 119333 Moscow, Russia; (E.U.P.); (Y.A.Z.); (A.S.K.); (V.N.D.)
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15
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Pan Y, Bu T, Deng X, Jia J, Yuan G. Gut microbiota and type 2 diabetes mellitus: a focus on the gut-brain axis. Endocrine 2024; 84:1-15. [PMID: 38227168 DOI: 10.1007/s12020-023-03640-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 11/30/2023] [Indexed: 01/17/2024]
Abstract
Type 2 diabetes mellitus (T2DM) has become one of the most serious public healthcare challenges, contributing to increased mortality and disability. In the past decades, significant progress has been made in understanding the pathogenesis of T2DM. Mounting evidence suggested that gut microbiota (GM) plays a significant role in the development of T2DM. Communication between the GM and the brain is a complex bidirectional connection, known as the "gut-brain axis," via the nervous, neuroendocrine, and immune systems. Gut-brain axis has an essential impact on various physiological processes, including glucose metabolism, food intake, gut motility, etc. In this review, we provide an outline of the gut-brain axis. We also highlight how the dysbiosis of the gut-brain axis affects glucose homeostasis and even results in T2DM.
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Affiliation(s)
- Yi Pan
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Tong Bu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xia Deng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Jue Jia
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Guoyue Yuan
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang, Jiangsu, China.
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16
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Rajkumar RP. Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration. EXPLORATION OF NEUROPROTECTIVE THERAPY 2024:11-37. [DOI: 10.37349/ent.2024.00068] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 12/12/2023] [Indexed: 01/03/2025]
Abstract
Depression is a known risk factor for dementia. Antidepressants are the most commonly used treatment for this condition, and are effective in at least half to two-thirds of cases. Extensive evidence from in vitro and animal models suggests that antidepressants have anti-inflammatory and neuroprotective properties. These effects have been shown to reduce the oxidative damage, amyloid aggregation, and expression of pro-inflammatory genes associated with animal models of neurodegenerative disorders. However, longitudinal research in humans has shown that antidepressants do not protect against dementia, and may even be associated with a risk of cognitive deterioration over time in older adults. The contrast between two sets of findings represents a paradox of significant clinical and public health significance, particularly when treating depression in late life. This review paper attempts to resolve this paradox by critically reviewing the medium- and long-term effects of antidepressants on peripheral immune-inflammatory responses, infection risk, gut microbiota, and neuroendocrine responses to stress, and how these effects may influence the risk of neurodegeneration. Briefly stated, it is possible that the peripheral actions of antidepressant medications may antagonize their beneficial effects against neuroinflammation. The implications of these findings are then explored with a particular focus on the development and testing of multimodal neuroprotective and anti-inflammatory treatments that could reduce the risk of Alzheimer’s and related dementias in patients suffering from depression.
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Affiliation(s)
- Ravi Philip Rajkumar
- Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, Pondicherry, India
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17
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Ardi Z, Putra AH, Murni AW, Eseadi C, Otu MS, Yetis H, Barabanova E. Determining Risk Factors for Functional Gastrointestinal Disorder among Muslim University Students in Indonesia. ISLAMIC GUIDANCE AND COUNSELING JOURNAL 2024; 7. [DOI: 10.25217/0020247431600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Abstract
Functional gastrointestinal disorders (FGIDs) are disorders of the gastrointestinal tract without a clear structural or biochemical cause. FGIDs can interfere with a person's daily life. Several psychological conditions can cause FGIDs as psychosomatic disorders. Five factors are thought to affect a person's FGID condition, namely Generalized Anxiety Disorder (GAD), life satisfaction, perceived stress, perceived social support, and religiosity. This study aims to analyze the determinants of FGID conditions and the role of religiosity as a moderator variable. This study used a quantitative approach with correlation methods. A total of 383 Indonesian Muslim students participated as respondents in this study. The instruments used in this study were the life satisfaction scale, perceived stress-10 scale, perceived social support multidimensional scale, GAD-7, Duke University Religion Index, and FGID scale. Research data were collected online from research respondents. Furthermore, the research data analysis technique used was partial structural equation modeling (PLS-SEM). The results of this study indicate that GAD, life satisfaction, and perceived stress are determinants of FGID conditions in Indonesian Muslim students. The results also show that religiosity acts as a moderator variable in the influence of GAD conditions on a person's FGID condition.
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18
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Sah RK, Nandan A, Kv A, S P, S S, Jose A, Venkidasamy B, Nile SH. Decoding the role of the gut microbiome in gut-brain axis, stress-resilience, or stress-susceptibility: A review. Asian J Psychiatr 2024; 91:103861. [PMID: 38134565 DOI: 10.1016/j.ajp.2023.103861] [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: 08/17/2023] [Revised: 12/01/2023] [Accepted: 12/08/2023] [Indexed: 12/24/2023]
Abstract
Increased exposure to stress is associated with stress-related disorders, including depression, anxiety, and neurodegenerative conditions. However, susceptibility to stress is not seen in every individual exposed to stress, and many of them exhibit resilience. Thus, developing resilience to stress could be a big breakthrough in stress-related disorders, with the potential to replace or act as an alternative to the available therapies. In this article, we have focused on the recent advancements in gut microbiome research and the potential role of the gut-brain axis (GBA) in developing resilience or susceptibility to stress. There might be a complex interaction between the autonomic nervous system (ANS), immune system, endocrine system, microbial metabolites, and bioactive lipids like short-chain fatty acids (SCFAs), neurotransmitters, and their metabolites that regulates the communication between the gut microbiota and the brain. High fiber intake, prebiotics, probiotics, plant supplements, and fecal microbiome transplant (FMT) could be beneficial against gut dysbiosis-associated brain disorders. These could promote the growth of SCFA-producing bacteria, thereby enhancing the gut barrier and reducing the gut inflammatory response, increase the expression of the claudin-2 protein associated with the gut barrier, and maintain the blood-brain barrier integrity by promoting the expression of tight junction proteins such as claudin-5. Their neuroprotective effects might also be related to enhancing the expression of brain-derived neurotrophic factor (BDNF) and glucagon-like peptide (GLP-1). Further investigations are needed in the field of the gut microbiome for the elucidation of the mechanisms by which gut dysbiosis contributes to the pathophysiology of neuropsychiatric disorders.
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Affiliation(s)
- Ranjay Kumar Sah
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India
| | - Amritasree Nandan
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India
| | - Athira Kv
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India.
| | - Prashant S
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, Kerala, India
| | - Sathianarayanan S
- NITTE (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Mangalore, India
| | - Asha Jose
- JSS College of Pharmacy, JSS Academy of Higher Education and research, Ooty 643001, Tamil Nadu, India
| | - Baskar Venkidasamy
- Department of Oral & Maxillofacial Surgery, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600 077, Tamil Nadu, India.
| | - Shivraj Hariram Nile
- Division of Food and Nutritional Biotechnology, National Agri-Food Biotechnology Institute (NABI), Sector-81, Mohali 140306, Punjab, India.
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Hu X, He Z, Zhao C, He Y, Qiu M, Xiang K, Zhang N, Fu Y. Gut/rumen-mammary gland axis in mastitis: Gut/rumen microbiota-mediated "gastroenterogenic mastitis". J Adv Res 2024; 55:159-171. [PMID: 36822391 PMCID: PMC10770137 DOI: 10.1016/j.jare.2023.02.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/25/2023] [Accepted: 02/13/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Mastitis is an inflammatory response in the mammary gland that results in huge economic losses in the breeding industry. The aetiology of mastitis is complex, and the pathogenesis has not been fully elucidated. It is commonly believed that mastitis is induced by pathogen infection of the mammary gland and induces a local inflammatory response. However, in the clinic, mastitis is often comorbid or secondary to gastric disease, and local control effects targeting the mammary gland are limited. In addition, recent studies have found that the gut/rumen microbiota contributes to the development of mastitis and proposed the gut/rumen-mammary gland axis. Combined with studies indicating that gut/rumen microbiota disturbance can damage the gut mucosa barrier, gut/rumen bacteria and their metabolites can migrate to distal extraintestinal organs. It is believed that the occurrence of mastitis is related not only to the infection of the mammary gland by external pathogenic microorganisms but also to a gastroenterogennic pathogenic pathway. AIM OF REVIEW We propose the pathological concept of "gastroenterogennic mastitis" and believe that the gut/rumen-mammary gland axis-mediated pathway is the pathological mechanism of "gastroenterogennic mastitis". KEY SCIENTIFIC CONCEPTS OF REVIEW To clarify the concept of "gastroenterogennic mastitis" by summarizing reports on the effect of the gut/rumen microbiota on mastitis and the gut/rumen-mammary gland axis-mediated pathway to provide a research basis and direction for further understanding and solving the pathogenesis and difficulties encountered in the prevention of mastitis.
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Affiliation(s)
- Xiaoyu Hu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China
| | - Zhaoqi He
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China
| | - Caijun Zhao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China
| | - Yuhong He
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China
| | - Min Qiu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China
| | - Kaihe Xiang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China
| | - Naisheng Zhang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China.
| | - Yunhe Fu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China.
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20
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Andriolo IRL, Longo B, de Melo DM, de Souza MM, Prediger RD, da Silva LM. Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2024; 23:1371-1391. [PMID: 38500273 DOI: 10.2174/0118715273289138240306050532] [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: 12/12/2023] [Revised: 01/26/2024] [Accepted: 02/06/2024] [Indexed: 03/20/2024]
Abstract
INTRODUCTION Multiple illnesses commonly involve both the Central Nervous System (CNS) and the Gastrointestinal Tract (GI) simultaneously. Consistent evidence suggests that neurological disorders impair GI tract function and worsen the symptomatology and pathophysiology of digestive disorders. On the other hand, it has been proposed that early functional changes in the GI tract contribute to the genesis of several CNS illnesses. Additionally, the role played by the gut in these diseases can be seen as a paradigm for how the gut and the brain interact. METHODS We mentioned significant GI symptoms and discussed how the GI tract affects central nervous system illnesses, including depression, anxiety, Alzheimer's disease, and Parkinson's disease in this study. We also explored potential pathophysiological underpinnings and novel targets for the creation of future therapies targeted at gut-brain connections. RESULTS & DISCUSSION In this situation, modulating the gut microbiota through the administration of fecal microbiota transplants or probiotics may represent a new therapeutic option for this population, not only to treat GI problems but also behavioral problems, given the role that dysbiosis and leaky gut play in many neurological disorders. CONCLUSION Accurate diagnosis and treatment of co-existing illnesses also require coordination between psychiatrists, neurologists, gastroenterologists, and other specialties, as well as a thorough history and thorough physical examination.
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Affiliation(s)
| | - Bruna Longo
- Graduate Program in Pharmaceutical Sciences, University of Vale do Itajaí, Itajaí, Santa Catarina, Brazil
| | - Dayse Machado de Melo
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Márcia Maria de Souza
- Graduate Program in Pharmaceutical Sciences, University of Vale do Itajaí, Itajaí, Santa Catarina, Brazil
| | - Rui Daniel Prediger
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Luisa Mota da Silva
- Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil
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21
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He Z, Zhao C, He Y, Liu Z, Fan G, Zhu K, Wang Y, Zhang N, Fu Y, Hu X. Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway. J Anim Sci Biotechnol 2023; 14:157. [PMID: 38124149 PMCID: PMC10731779 DOI: 10.1186/s40104-023-00952-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 10/16/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in 'gastroenterogenic mastitis'. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that 'gastroenterogenic mastitis' can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis. RESULTS First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway. CONCLUSIONS In conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
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Affiliation(s)
- Zhaoqi He
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Caijun Zhao
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Yuhong He
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Zhuoyu Liu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Guyue Fan
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Kun Zhu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Yiqi Wang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Naisheng Zhang
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Yunhe Fu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China
| | - Xiaoyu Hu
- Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin Province, China.
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22
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Calabrò S, Kankowski S, Cescon M, Gambarotta G, Raimondo S, Haastert-Talini K, Ronchi G. Impact of Gut Microbiota on the Peripheral Nervous System in Physiological, Regenerative and Pathological Conditions. Int J Mol Sci 2023; 24:ijms24098061. [PMID: 37175764 PMCID: PMC10179357 DOI: 10.3390/ijms24098061] [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: 04/03/2023] [Revised: 04/21/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
It has been widely demonstrated that the gut microbiota is responsible for essential functions in human health and that its perturbation is implicated in the development and progression of a growing list of diseases. The number of studies evaluating how the gut microbiota interacts with and influences other organs and systems in the body and vice versa is constantly increasing and several 'gut-organ axes' have already been defined. Recently, the view on the link between the gut microbiota (GM) and the peripheral nervous system (PNS) has become broader by exceeding the fact that the PNS can serve as a systemic carrier of GM-derived metabolites and products to other organs. The PNS as the communication network between the central nervous system and the periphery of the body and internal organs can rather be affected itself by GM perturbation. In this review, we summarize the current knowledge about the impact of gut microbiota on the PNS, with regard to its somatic and autonomic divisions, in physiological, regenerative and pathological conditions.
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Affiliation(s)
- Sonia Calabrò
- Department of Molecular Medicine, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy
- Department of Biology, University of Padova, Viale G. Colombo 3, 35131 Padova, Italy
| | - Svenja Kankowski
- Hannover Medical School, Institute of Neuroanatomy and Cell Biology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
| | - Matilde Cescon
- Department of Molecular Medicine, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy
| | - Giovanna Gambarotta
- Department of Clinical and Biological Sciences & Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Regione Gonzole 10, Orbassano, 10043 Torino, Italy
| | - Stefania Raimondo
- Department of Clinical and Biological Sciences & Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Regione Gonzole 10, Orbassano, 10043 Torino, Italy
| | - Kirsten Haastert-Talini
- Hannover Medical School, Institute of Neuroanatomy and Cell Biology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
- Center for Systems Neuroscience Hannover (ZSN), Buenteweg 2, 30559 Hannover, Germany
| | - Giulia Ronchi
- Department of Clinical and Biological Sciences & Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Regione Gonzole 10, Orbassano, 10043 Torino, Italy
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23
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Sharkey KA, Mawe GM. The enteric nervous system. Physiol Rev 2023; 103:1487-1564. [PMID: 36521049 PMCID: PMC9970663 DOI: 10.1152/physrev.00018.2022] [Citation(s) in RCA: 138] [Impact Index Per Article: 69.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 12/12/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022] Open
Abstract
Of all the organ systems in the body, the gastrointestinal tract is the most complicated in terms of the numbers of structures involved, each with different functions, and the numbers and types of signaling molecules utilized. The digestion of food and absorption of nutrients, electrolytes, and water occurs in a hostile luminal environment that contains a large and diverse microbiota. At the core of regulatory control of the digestive and defensive functions of the gastrointestinal tract is the enteric nervous system (ENS), a complex system of neurons and glia in the gut wall. In this review, we discuss 1) the intrinsic neural control of gut functions involved in digestion and 2) how the ENS interacts with the immune system, gut microbiota, and epithelium to maintain mucosal defense and barrier function. We highlight developments that have revolutionized our understanding of the physiology and pathophysiology of enteric neural control. These include a new understanding of the molecular architecture of the ENS, the organization and function of enteric motor circuits, and the roles of enteric glia. We explore the transduction of luminal stimuli by enteroendocrine cells, the regulation of intestinal barrier function by enteric neurons and glia, local immune control by the ENS, and the role of the gut microbiota in regulating the structure and function of the ENS. Multifunctional enteric neurons work together with enteric glial cells, macrophages, interstitial cells, and enteroendocrine cells integrating an array of signals to initiate outputs that are precisely regulated in space and time to control digestion and intestinal homeostasis.
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Affiliation(s)
- Keith A Sharkey
- Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Gary M Mawe
- Department of Neurological Sciences, Larner College of Medicine, University of Vermont, Burlington, Vermont
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24
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Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P. Gut microbiota and its metabolites in depression: from pathogenesis to treatment. EBioMedicine 2023; 90:104527. [PMID: 36963238 PMCID: PMC10051028 DOI: 10.1016/j.ebiom.2023.104527] [Citation(s) in RCA: 238] [Impact Index Per Article: 119.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 02/13/2023] [Accepted: 03/02/2023] [Indexed: 03/26/2023] Open
Abstract
Major depressive disorder is one of the most disabling mental disorders worldwide. Increasing preclinical and clinical studies have highlighted that compositional and functional (e.g., metabolite) changes in gut microbiota, known as dysbiosis, are associated with the onset and progression of depression via regulating the gut-brain axis. However, the gut microbiota and their metabolites present a double-edged sword in depression. Dysbiosis is involved in the pathogenesis of depression while, at the same time, offering a novel therapeutic target. In this review, we describe the association between dysbiosis and depression, drug-microbiota interactions in antidepressant treatment, and the potential health benefits of microbial-targeted therapeutics in depression, including dietary interventions, fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and postbiotics. With the emergence of microbial research, we describe a new direction for future research and clinical treatment of depression.
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Affiliation(s)
- Lanxiang Liu
- Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Haiyang Wang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, 401147, China
| | - Xueyi Chen
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Yangdong Zhang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Hanping Zhang
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Peng Xie
- Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China; NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University, 401147, China.
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25
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Ganz J, Ratcliffe EM. Who's talking to whom: microbiome-enteric nervous system interactions in early life. Am J Physiol Gastrointest Liver Physiol 2023; 324:G196-G206. [PMID: 36625480 PMCID: PMC9988524 DOI: 10.1152/ajpgi.00166.2022] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 12/22/2022] [Accepted: 01/04/2023] [Indexed: 01/11/2023]
Abstract
The enteric nervous system (ENS) is the intrinsic nervous system of the gastrointestinal tract (GI) and regulates important GI functions, including motility, nutrient uptake, and immune response. The development of the ENS begins during early organogenesis and continues to develop once feeding begins, with ongoing plasticity into adulthood. There has been increasing recognition that the intestinal microbiota and ENS interact during critical periods, with implications for normal development and potential disease pathogenesis. In this review, we focus on insights from mouse and zebrafish model systems to compare and contrast how each model can serve in elucidating the bidirectional communication between the ENS and the microbiome. At the end of this review, we further outline implications for human disease and highlight research innovations that can lead the field forward.
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Affiliation(s)
- Julia Ganz
- Department of Integrative Biology, Michigan State University, East Lansing, Michigan, United States
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26
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Liu X, Yang L, Li G, Jiang Y, Zhang G, Ling J. A novel promising neuroprotective agent: Ganoderma lucidum polysaccharide. Int J Biol Macromol 2023; 229:168-180. [PMID: 36587634 DOI: 10.1016/j.ijbiomac.2022.12.276] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 12/20/2022] [Accepted: 12/24/2022] [Indexed: 12/30/2022]
Abstract
Nervous system diseases (NSDs) are characterized by a wide range of symptoms, a complex pathophysiology, an unclear etiology, a great deal of variation in treatment response, and lengthy therapy cycles, all of which pose considerable hurdles to clinical treatment. A traditional valuable medicine known as Ganoderma lucidum (GL) has a significant role to play in preserving health and treating diseases. Ganoderma lucidum polysaccharides (GLP) is one of the cardinal effective active ingredients of GL, which has a number of pharmacological actions, including liver protection, immune regulation, antioxidant activity, anticancer activity, antibacterial activity, and antiviral activity. Recently, studies on the structural characterization and biological functions of GLP were presented in this article to review the progress of researches about GLP on NSDs and summarize the potential mechanisms of action. These studies were anticipated to provide new research ideas for GLP as a novel promising neuroprotective agent and provide a reference for better development and utilization of GLP.
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Affiliation(s)
- Xiaojin Liu
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Department of Pharmacy, Shandong Medical College, Linyi 276000, China
| | - Luodan Yang
- College of Physical Education and Sports Science, South China Normal University, Guangzhou 510006, China
| | - Guangyao Li
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Yingnan Jiang
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Guoying Zhang
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
| | - Jianya Ling
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
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27
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Chen YC, Lin HY, Chien Y, Tung YH, Ni YH, Gau SSF. Altered gut microbiota correlates with behavioral problems but not gastrointestinal symptoms in individuals with autism. Brain Behav Immun 2022; 106:161-178. [PMID: 36058421 DOI: 10.1016/j.bbi.2022.08.015] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 08/09/2022] [Accepted: 08/28/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Despite inconsistent results across studies, emerging evidence suggests that the microbial micro-environment may be associated with autism spectrum disorder (ASD). Geographical and cultural factors highly impact microbial profiles, and there is a shortage of data from East Asian populations. This study aimed to comprehensively characterize microbial profiles in an East Asian sample and explore whether gut microbiota contributes to clinical symptoms, emotional/behavioral problems, and GI symptoms in ASD. METHODS We assessed 82 boys and young men with ASD and 31 typically developing controls (TDC), aged 6-25 years. We analyzed the stool sample of all participants with 16S V3-V4 rRNA sequencing and correlated its profile with GI symptoms, autistic symptoms, and emotional/behavioral problems. RESULTS Autistic individuals, compared to TDC, had worse GI symptoms. There were no group differences in alpha diversity of species richness estimates (Shannon-wiener and Simpson diversity indices). Participants with ASD had an increased relative abundance of Fusobacterium, Ruminococcus torques group (at the genus level), and Bacteroides plebeius DSM 17135 (at the species level), while a decreased relative abundance of Ruminococcaceae UCG 013, Ervsipelotrichaceae UCG 003, Parasutterella, Clostridium sensu stricto 1, Turicibacter (at the genus level), and Clostridium spiroforme DSM 1552 and Intestinimonas butyriciproducens (at the species level). Altered taxonomic diversity in ASD significantly correlated with autistic symptoms, thought problems, delinquent behaviors, self dysregulation, and somatic complaints. We did not find an association between gut symptoms and gut microbial dysbiosis. CONCLUSIONS Our findings suggest that altered microbiota are associated with behavioral phenotypes but not GI symptoms in ASD. The function of the identified microbial profiles mainly involves the immune pathway, supporting the hypothesis of a complex relationship between altered microbiome, immune dysregulation, and ASD that may advance the discovery of molecular biomarkers for ASD.
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Affiliation(s)
- Yu-Chieh Chen
- Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hsiang-Yuan Lin
- Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Yiling Chien
- Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yu-Hung Tung
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan
| | - Susan Shur-Fen Gau
- Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
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28
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Pan R, Wang L, Xu X, Chen Y, Wang H, Wang G, Zhao J, Chen W. Crosstalk between the Gut Microbiome and Colonic Motility in Chronic Constipation: Potential Mechanisms and Microbiota Modulation. Nutrients 2022; 14:nu14183704. [PMID: 36145079 PMCID: PMC9505360 DOI: 10.3390/nu14183704] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/05/2022] [Accepted: 09/06/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic constipation (CC) is a highly prevalent and burdensome gastrointestinal disorder. Accumulating evidence highlights the link between imbalances in the gut microbiome and constipation. However, the mechanisms by which the microbiome and microbial metabolites affect gut movement remain poorly understood. In this review, we discuss recent studies on the alteration in the gut microbiota in patients with CC and the effectiveness of probiotics in treating gut motility disorder. We highlight the mechanisms that explain how the gut microbiome and its metabolism are linked to gut movement and how intestinal microecological interventions may counteract these changes based on the enteric nervous system, the central nervous system, the immune function, and the ability to modify intestinal secretion and the hormonal milieu. In particular, microbiota-based approaches that modulate the levels of short-chain fatty acids and tryptophan catabolites or that target the 5-hydroxytryptamine and Toll-like receptor pathways may hold therapeutic promise. Finally, we discuss the existing limitations of microecological management in treating constipation and suggest feasible directions for future research.
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Affiliation(s)
- Ruili Pan
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Linlin Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xiaopeng Xu
- The Department of Clinical Laboratory, Wuxi Xishan People’s Hospital, Wuxi 214105, China
| | - Ying Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Haojue Wang
- The Department of of Obstetrics and Gynecology, Wuxi Xishan People’s Hospital, Wuxi 214105, China
- Correspondence: (H.W.); (J.Z.); Tel.: +86-510-8240-2084 (H.W.); +86-510-8591-2155 (J.Z.)
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
- Correspondence: (H.W.); (J.Z.); Tel.: +86-510-8240-2084 (H.W.); +86-510-8591-2155 (J.Z.)
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
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Ahmed H, Leyrolle Q, Koistinen V, Kärkkäinen O, Layé S, Delzenne N, Hanhineva K. Microbiota-derived metabolites as drivers of gut-brain communication. Gut Microbes 2022; 14:2102878. [PMID: 35903003 PMCID: PMC9341364 DOI: 10.1080/19490976.2022.2102878] [Citation(s) in RCA: 168] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut-brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut-brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut-brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood-brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins.
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Affiliation(s)
- Hany Ahmed
- Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland,CONTACT Hany Ahmed Food Chemistry and Food Development Unit, Department of Life Technologies, University of Turku, Turku, Finland
| | - Quentin Leyrolle
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
| | - Ville Koistinen
- Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland,School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Olli Kärkkäinen
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Sophie Layé
- Laboratoire NutriNeuro, UMR INRAE 1286, Bordeaux INP, Université de Bordeaux, Bordeaux, France
| | - Nathalie Delzenne
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Brussels, Belgium
| | - Kati Hanhineva
- Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland,School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland,Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden
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30
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Abot A, Fried S, Cani PD, Knauf C. Reactive Oxygen Species/Reactive Nitrogen Species as Messengers in the Gut: Impact on Physiology and Metabolic Disorders. Antioxid Redox Signal 2022; 37:394-415. [PMID: 34714099 DOI: 10.1089/ars.2021.0100] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Significance: The role of reactive oxygen/nitrogen species as "friend" or "foe" messengers in the whole body is well characterized. Depending on the concentration in the tissue considered, these molecular actors exert beneficial or deleterious impacts leading to a pathological state, as observed in metabolic disorders such as type 2 diabetes and obesity. Recent Advances: Among the tissues impacted by oxidation and inflammation in this pathological state, the intestine is a site of dysfunction that can establish diabetic symptoms, such as alterations in the intestinal barrier, gut motility, microbiota composition, and gut/brain axis communication. In the intestine, reactive oxygen/nitrogen species (from the host and/or microbiota) are key factors that modulate the transition from physiological to pathological signaling. Critical Issues: Controlling the levels of intestinal reactive oxygen/nitrogen species is a complicated balance between positive and negative impacts that is in constant equilibrium. Here, we describe the synthesis and degradation of intestinal reactive oxygen/nitrogen species and their interactions with the host. The development of novel redox-based therapeutics that alter these processes could restore intestinal health in patients with metabolic disorders. Future Directions: Deciphering the mode of action of reactive oxygen/nitrogen species in the gut of obese/diabetic patients could result in a future therapeutic strategy that combines nutritional and pharmacological approaches. Consequently, preventive and curative treatments must take into account one of the first sites of oxidative and inflammatory dysfunctions in the body, that is, the intestine. Antioxid. Redox Signal. 37, 394-415.
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Affiliation(s)
- Anne Abot
- Université Paul Sabatier, Toulouse III, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan, Toulouse, France.,International Research Project (IRP), European Lab "NeuroMicrobiota," Brussels, Belgium and Toulouse, France
| | - Steven Fried
- Université Paul Sabatier, Toulouse III, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan, Toulouse, France.,International Research Project (IRP), European Lab "NeuroMicrobiota," Brussels, Belgium and Toulouse, France
| | - Patrice D Cani
- International Research Project (IRP), European Lab "NeuroMicrobiota," Brussels, Belgium and Toulouse, France.,UCLouvain, Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO, Walloon Excellence in Life Sciences and BIOtechnology, Metabolism and Nutrition Research Group, Brussels, Belgium
| | - Claude Knauf
- Université Paul Sabatier, Toulouse III, INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), CHU Purpan, Toulouse, France.,International Research Project (IRP), European Lab "NeuroMicrobiota," Brussels, Belgium and Toulouse, France
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Du Y, Li X, An Y, Song Y, Lu Y. Association of gut microbiota with sort-chain fatty acids and inflammatory cytokines in diabetic patients with cognitive impairment: A cross-sectional, non-controlled study. Front Nutr 2022; 9:930626. [PMID: 35938126 PMCID: PMC9355148 DOI: 10.3389/fnut.2022.930626] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/30/2022] [Indexed: 12/12/2022] Open
Abstract
Emerging evidence suggests that gut microbiota, short-chain fatty acids (SCFAs), and inflammatory cytokines play important roles in the pathogenesis of diabetic cognitive impairment (DCI). However, little is known about alterations of gut microbiota and SCFA levels as well as the relationships between inflammatory cytokines and cognitive function in Chinese DCI patients. Herein, the differences in the gut microbiota, plasma SCFAs, and inflammatory cytokines in DCI patients and type 2 diabetes mellitus (T2DM) patients were explored. A cross-sectional study of 30 DCI patients and 30 T2DM patients without mild cognitive impairment (MCI) was conducted in Tianjin city, China. The gut microbiota, plasma SCFAs, and inflammatory cytokines were determined using 16S ribosomal RNA (rRNA) gene sequencing, gas chromatography-mass spectrometry (GC-MS), and Luminex immunofluorescence assays, respectively. In addition, the correlation between gut microbiota and DCI clinical characteristics, SCFAs, and inflammatory cytokines was investigated. According to the results, at the genus level, DCI patients presented a greater abundance of Gemmiger, Bacteroides, Roseburia, Prevotella, and Bifidobacterium and a poorer abundance of Escherichia and Akkermansia than T2DM patients. The plasma concentrations of acetic acid, propionic acid, isobutyric acid, and butyric acid plummeted in DCI patients compared to those in T2DM patients. TNF-α and IL-8 concentrations in plasma were significantly higher in DCI patients than in T2DM patients. Moreover, the concentrations of acetic acid, propionic acid, butyric acid, and isovaleric acid in plasma were negatively correlated with TNF-α, while those of acetic acid and butyric acid were negatively correlated with IL-8. Furthermore, the abundance of the genus Alloprevotella was negatively correlated with butyric acid, while that of Holdemanella was negatively correlated with propanoic acid and isobutyric acid. Fusobacterium abundance was negatively correlated with propanoic acid. Clostridium XlVb abundance was negatively correlated with TNF-α, while Shuttleworthia abundance was positively correlated with TNF-α. It was demonstrated that the gut microbiota alterations were accompanied by a change in SCFAs and inflammatory cytokines in DCI in Chinese patients, potentially causing DCI development. These findings might help to identify more effective microbiota-based therapies for DCI in the future.
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Affiliation(s)
- Yage Du
- School of Nursing, Peking University, Beijing, China
| | - Xiaoying Li
- Geriatrics Department, Beijing Jishuitan Hospital, Beijing, China
| | - Yu An
- Endocrinology Department, Beijing Chaoyang Hospital, Beijing, China
| | - Ying Song
- School of Nursing, Peking University, Beijing, China
| | - Yanhui Lu
- School of Nursing, Peking University, Beijing, China
- *Correspondence: Yanhui Lu
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Yu F, Hou ZS, Luo HR, Cui XF, Xiao J, Kim YB, Li JL, Feng WR, Tang YK, Li HX, Su SY, Song CY, Wang MY, Xu P. Zinc alters behavioral phenotypes, neurotransmitter signatures, and immune homeostasis in male zebrafish (Danio rerio). THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 828:154099. [PMID: 35240190 DOI: 10.1016/j.scitotenv.2022.154099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 02/14/2022] [Accepted: 02/19/2022] [Indexed: 06/14/2023]
Abstract
Anthropogenic activities discharge zinc into aquatic ecosystems, and the effects of long-term and low-concentration zinc exposure on fish behavior are unclear. We evaluated the behavior and physiology of male zebrafish (Danio rerio) after a 6-week exposure to 1.0 or 1.5 ppm (mg/L) zinc chloride. The exposure caused anxiety-like behaviors and altered the social preferences in both exposure groups. Analysis of transcriptional changes suggested that in the brain, zinc exerted heterogenetic effects on immune and neurotransmitter functions. Exposure to 1.0 ppm zinc chloride resulted in constitutive immune dyshomeostasis, while exposure to 1.5 ppm zinc chloride impaired the neurotransmitter glutamate. In the intestine, zinc dysregulated self-renewal of intestinal cells, a potential loss of defense function. Moreover, exposure to 1.5 ppm zinc chloride suppressed intestinal immune functions and dysregulated tyrosine metabolism. These behavioral alterations suggested that the underlying mechanisms were distinct and concentration-specific. Overall, environmental levels of zinc can alter male zebrafish behaviors by dysregulating neurotransmitter and immunomodulation signatures.
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Affiliation(s)
- Fan Yu
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
| | - Zhi-Shuai Hou
- Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao 266003, China; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
| | - Hong-Rui Luo
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Xue-Fan Cui
- State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Jun Xiao
- Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Academy of Fishery Sciences, Nanning 530021, China
| | - Young-Bum Kim
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
| | - Jian-Lin Li
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Wen-Rong Feng
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Yong-Kai Tang
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Hong-Xia Li
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Sheng-Yan Su
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Chang-You Song
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Mei-Yao Wang
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Pao Xu
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
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Wemelle E, Carneiro L, Abot A, Lesage J, Cani PD, Knauf C. Glucose Stimulates Gut Motility in Fasted and Fed Conditions: Potential Involvement of a Nitric Oxide Pathway. Nutrients 2022; 14:nu14102176. [PMID: 35631317 PMCID: PMC9143273 DOI: 10.3390/nu14102176] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/19/2022] [Accepted: 05/19/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: Type 2 diabetes (T2D) is associated with a duodenal hypermotility in postprandial conditions that favors hyperglycemia and insulin resistance via the gut-brain axis. Enterosynes, molecules produced within the gut with effects on the enteric nervous system, have been recently discovered and pointed to as potential key modulators of the glycemia. Indeed, targeting the enteric nervous system that controls gut motility is now considered as an innovative therapeutic way in T2D to limit intestinal glucose absorption and restore the gut-brain axis to improve insulin sensitivity. So far, little is known about the role of glucose on duodenal contraction in fasted and fed states in normal and diabetic conditions. The aim of the present study was thus to investigate these effects in adult mice. (2) Methods: Gene-expression level of glucose transporters (SGLT-1 and GLUT2) were quantified in the duodenum and jejunum of normal and diabetic mice fed with an HFD. The effect of glucose at different concentrations on duodenal and jejunal motility was studied ex vivo using an isotonic sensor in fasted and fed conditions in both normal chow and HFD mice. (3) Results: Both SGLT1 and GLUT2 expressions were increased in the duodenum (47 and 300%, respectively) and jejunum (75% for GLUT2) of T2D mice. We observed that glucose stimulates intestinal motility in fasted (200%) and fed (400%) control mice via GLUT2 by decreasing enteric nitric oxide release (by 600%), a neurotransmitter that inhibits gut contractions. This effect was not observed in diabetic mice, suggesting that glucose sensing and mechanosensing are altered during T2D. (4) Conclusions: Glucose acts as an enterosyne to control intestinal motility and glucose absorption through the enteric nervous system. Our data demonstrate that GLUT2 and a reduction of NO production could both be involved in this stimulatory contracting effect.
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Affiliation(s)
- Eve Wemelle
- INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), Université Paul Sabatier, Toulouse III, CHU Purpan, Place du Docteur Baylac, CS 60039, CEDEX 3, 31024 Toulouse, France; (E.W.); (L.C.)
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, 31024 Toulouse, France
| | - Lionel Carneiro
- INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), Université Paul Sabatier, Toulouse III, CHU Purpan, Place du Docteur Baylac, CS 60039, CEDEX 3, 31024 Toulouse, France; (E.W.); (L.C.)
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, 31024 Toulouse, France
| | - Anne Abot
- Enterosys SAS, 31670 Labège, France;
| | - Jean Lesage
- Université de Lille, Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, F-59000 Lille, France;
| | - Patrice D. Cani
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, 31024 Toulouse, France
- UCLouvain, Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO, Walloon Excellence in Life Sciences and BIOtechnology, Metabolism and Nutrition Research Group, 1200 Brussels, Belgium
- Correspondence: (P.D.C.); (C.K.)
| | - Claude Knauf
- INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), Université Paul Sabatier, Toulouse III, CHU Purpan, Place du Docteur Baylac, CS 60039, CEDEX 3, 31024 Toulouse, France; (E.W.); (L.C.)
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, 31024 Toulouse, France
- Correspondence: (P.D.C.); (C.K.)
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Uncovering bidirectional brain-body interactions in health and disease. Neuropharmacology 2022; 212:109073. [DOI: 10.1016/j.neuropharm.2022.109073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Martinou E, Stefanova I, Iosif E, Angelidi AM. Neurohormonal Changes in the Gut-Brain Axis and Underlying Neuroendocrine Mechanisms following Bariatric Surgery. Int J Mol Sci 2022; 23:3339. [PMID: 35328759 PMCID: PMC8954280 DOI: 10.3390/ijms23063339] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 02/05/2023] Open
Abstract
Obesity is a complex, multifactorial disease that is a major public health issue worldwide. Currently approved anti-obesity medications and lifestyle interventions lack the efficacy and durability needed to combat obesity, especially in individuals with more severe forms or coexisting metabolic disorders, such as poorly controlled type 2 diabetes. Bariatric surgery is considered an effective therapeutic modality with sustained weight loss and metabolic benefits. Numerous genetic and environmental factors have been associated with the pathogenesis of obesity, while cumulative evidence has highlighted the gut-brain axis as a complex bidirectional communication axis that plays a crucial role in energy homeostasis. This has led to increased research on the roles of neuroendocrine signaling pathways and various gastrointestinal peptides as key mediators of the beneficial effects following weight-loss surgery. The accumulate evidence suggests that the development of gut-peptide-based agents can mimic the effects of bariatric surgery and thus is a highly promising treatment strategy that could be explored in future research. This article aims to elucidate the potential underlying neuroendocrine mechanisms of the gut-brain axis and comprehensively review the observed changes of gut hormones associated with bariatric surgery. Moreover, the emerging role of post-bariatric gut microbiota modulation is briefly discussed.
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Affiliation(s)
- Eirini Martinou
- Department of Upper Gastrointestinal Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
| | - Irena Stefanova
- Department of General Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
| | - Evangelia Iosif
- Department of General Surgery, Royal Surrey County Hospital, Guildford GU2 7XX, UK;
| | - Angeliki M. Angelidi
- Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Korf JM, Ganesh BP, McCullough LD. Gut dysbiosis and age-related neurological diseases in females. Neurobiol Dis 2022; 168:105695. [PMID: 35307514 PMCID: PMC9631958 DOI: 10.1016/j.nbd.2022.105695] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 02/19/2022] [Accepted: 03/13/2022] [Indexed: 12/12/2022] Open
Abstract
Historically, females have been underrepresented in biological research. With increased interest in the gut microbiome and the gut-brain axis, it is important for researchers to pursue studies that consider sex as a biological variable. The composition of the gut microbiome is influenced by environmental factors, disease, diet, and varies with age and by sex. Detrimental changes in the gut microbiome, referred to as dysbiosis, is believed to influence the development and progression of age-related neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and stroke. Many are investigating the changes in microbial populations in order or to better understand the role of the gut immunity and the microbiome in neurodegenerative diseases, many of which the exact etiology remains elusive, and no cures exist. Others are working to find diagnostic markers for earlier detection, or to therapeutically modulate microbial populations using probiotics. However, while all these diseases present in reproductively senescent females, most studies only use male animals for their experimental design. Reproductively senescent females have been shown to have differences in disease progression, inflammatory responses, and microbiota composition, therefore, for research to be translational to affected populations it is necessary for appropriate models to be used. This review discusses factors that influence the gut microbiome and the gut brain axis in females, and highlights studies that have investigated the role of dysbiosis in age-related neurodegenerative disorders that have included females in their study design.
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Affiliation(s)
- Janelle M Korf
- Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77370, USA; University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 6767 Bertner Ave, Houston, TX 77030, USA.
| | - Bhanu P Ganesh
- Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77370, USA.
| | - Louise D McCullough
- Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77370, USA.
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37
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Panther EJ, Dodd W, Clark A, Lucke-Wold B. Gastrointestinal Microbiome and Neurologic Injury. Biomedicines 2022; 10:500. [PMID: 35203709 PMCID: PMC8962360 DOI: 10.3390/biomedicines10020500] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/16/2022] [Accepted: 02/18/2022] [Indexed: 02/05/2023] Open
Abstract
Communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS) is vital for maintaining systemic homeostasis. Intrinsic and extrinsic neurological inputs of the gut regulate blood flow, peristalsis, hormone release, and immunological function. The health of the gut microbiome plays a vital role in regulating the overall function and well-being of the individual. Microbes release short-chain fatty acids (SCFAs) that regulate G-protein-coupled receptors to mediate hormone release, neurotransmitter release (i.e., serotonin, dopamine, noradrenaline, γ-aminobutyric acid (GABA), acetylcholine, and histamine), and regulate inflammation and mood. Further gaseous factors (i.e., nitric oxide) are important in regulating inflammation and have a response in injury. Neurologic injuries such as ischemic stroke, spinal cord injury, traumatic brain injury, and hemorrhagic cerebrovascular lesions can all lead to gut dysbiosis. Additionally, unfavorable alterations in the composition of the microbiota may be associated with increased risk for these neurologic injuries due to increased proinflammatory molecules and clotting factors. Interventions such as probiotics, fecal microbiota transplantation, and oral SCFAs have been shown to stabilize and improve the composition of the microbiome. However, the effect this has on neurologic injury prevention and recovery has not been studied extensively. The purpose of this review is to elaborate on the complex relationship between the nervous system and the microbiome and to report how neurologic injury modulates the status of the microbiome. Finally, we will propose various interventions that may be beneficial in the recovery from neurologic injury.
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Affiliation(s)
- Eric J. Panther
- Department of Neurosurgery, University of Florida, Gainesville, FL 32601, USA;
| | - William Dodd
- College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (W.D.); (A.C.)
| | - Alec Clark
- College of Medicine, University of Central Florida, Orlando, FL 32816, USA; (W.D.); (A.C.)
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32601, USA;
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Grasset E, Puel A, Charpentier J, Klopp P, Christensen JE, Lelouvier B, Servant F, Blasco-Baque V, Tercé F, Burcelin R. Gut microbiota dysbiosis of type 2 diabetic mice impairs the intestinal daily rhythms of GLP-1 sensitivity. Acta Diabetol 2022; 59:243-258. [PMID: 34648088 DOI: 10.1007/s00592-021-01790-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023]
Abstract
The gut-brain-beta cell glucagon-like peptide-1 (GLP-1)-dependent axis and the clock genes both control insulin secretion. Evidence shows that a keystone of this molecular interaction could be the gut microbiota. We analyzed in mice the circadian profile of GLP-1 sensitivity on insulin secretion and the impact of the autonomic neuropathy, antibiotic treated in different diabetic mouse models and in germ-free colonized mice. We show that GLP-1sensitivity is maximal during the dark feeding period, i.e., the postprandial state. Coincidently, the ileum expression of GLP-1 receptor and peripherin is increased and tightly correlated with a subset of clock gene. Since both are markers of enteric neurons, it suggests a role in the gut-brain-beta cell GLP-1-dependent axis. We evaluated the importance of gut microbiota dysbiosis and found that the abundance of ileum bacteria, particularly Ruminococcaceae and Lachnospiraceae, oscillated diurnally, with a maximum during the dark period, along with expression patterns of a subset of clock genes. This diurnal pattern of circadian gene expression and Lachnospiraceae abundance was also observed in two separate mouse models of gut microbiota dysbiosis and of autonomic neuropathy with impaired GLP-1 sensitivity (1.high-fat diet-fed type 2 diabetic, 2.antibiotic-treated/germ-free mice). Our data show that GLP-1 sensitivity relies on specific pattern of intestinal clock gene expression and specific gut bacteria. This new statement opens opportunities to treat diabetic patient with GLP-1-based therapies by using on a possible pre/probiotic co-treatment to improve the time-dependent efficiency of these therapies.
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Affiliation(s)
- Estelle Grasset
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France.
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France.
| | - Anthony Puel
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Julie Charpentier
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Pascale Klopp
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Jeffrey E Christensen
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Benjamin Lelouvier
- Vaiomer SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670, Labège Innopole, France
| | - Florence Servant
- Vaiomer SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670, Labège Innopole, France
| | - Vincent Blasco-Baque
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - François Tercé
- Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France
- UMR) 1048, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2 : 'Intestinal Risk Factors, Diabetes, Université Paul Sabatier (UPS), Unité Mixte de Recherche, 31432, Toulouse Cedex 4, Dyslipidemia, France
| | - Rémy Burcelin
- Directeur de Recherche Inserm I²MC, Institut des Maladies Métaboliques et Cardiovasculaires, Inserm U 1027, Rue Jean Poulhès, 31400, Toulouse, France.
- Research Director Inserm I²MC, Institute for research on cardiometabolic diseases, Inserm U 1027, Rue Jean Poulhès, 31400, Toulouse, France.
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Irving H, Turek I, Kettle C, Yaakob N. Tapping into 5-HT 3 Receptors to Modify Metabolic and Immune Responses. Int J Mol Sci 2021; 22:ijms222111910. [PMID: 34769340 PMCID: PMC8584345 DOI: 10.3390/ijms222111910] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 10/28/2021] [Accepted: 10/29/2021] [Indexed: 02/07/2023] Open
Abstract
5-hydroxytryptamine type 3 (5-HT3) receptors are ligand gated ion channels, which clearly distinguish their mode of action from the other G-protein coupled 5-HT or serotonin receptors. 5-HT3 receptors are well established targets for emesis and gastrointestinal mobility and are used as adjunct targets in treating schizophrenia. However, the distribution of these receptors is wider than the nervous system and there is potential that these additional sites can be targeted to modulate inflammatory and/or metabolic conditions. Recent progress in structural biology and pharmacology of 5-HT3 receptors have provided profound insights into mechanisms of their action. These advances, combined with insights into clinical relevance of mutations in genes encoding 5-HT3 subunits and increasing understanding of their implications in patient's predisposition to diseases and response to the treatment, open new avenues for personalized precision medicine. In this review, we recap on the current status of 5-HT3 receptor-based therapies using a biochemical and physiological perspective. We assess the potential for targeting 5-HT3 receptors in conditions involving metabolic or inflammatory disorders based on recent findings, underscoring the challenges and limitations of this approach.
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Affiliation(s)
- Helen Irving
- Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Bendigo, VIC 3550, Australia; (I.T.); (C.K.)
- Correspondence:
| | - Ilona Turek
- Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Bendigo, VIC 3550, Australia; (I.T.); (C.K.)
| | - Christine Kettle
- Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Bendigo, VIC 3550, Australia; (I.T.); (C.K.)
| | - Nor Yaakob
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
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