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Yan R, Zhang L, Chen Y, Zheng Y, Xu P, Xu Z. Therapeutic potential of gut microbiota modulation in epilepsy: A focus on short-chain fatty acids. Neurobiol Dis 2025; 209:106880. [PMID: 40118219 DOI: 10.1016/j.nbd.2025.106880] [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: 11/17/2024] [Revised: 03/17/2025] [Accepted: 03/18/2025] [Indexed: 03/23/2025] Open
Abstract
According to the criteria established by the International League Against Epilepsy (ILAE), epilepsy is defined as a disorder characterized by at least two unprovoked seizures occurring more than 24 h apart. Its pathogenesis is closely related to various physiological and pathological factors. Advances in high-throughput metagenomic sequencing have increasingly highlighted the role of gut microbiota dysbiosis in epilepsy. Short-chain fatty acids (SCFAs), the major metabolites of the gut microbiota and key regulators of the gut-brain axis, support physiological homeostasis through multiple mechanisms. Recent studies have indicated that SCFAs not only regulate seizures by maintaining intestinal barrier integrity and modulating intestinal immune responses, but also affect the structure and function of the blood-brain barrier (BBB) and regulate neuroinflammation. This review, based on current literatures, explores the relationship between SCFAs and epilepsy, emphasizing how SCFAs affect epilepsy by modulating the intestinal barrier and BBB. In-depth studies on SCFAs may reveal their therapeutic potential and inform the development of gut microbiota-targeted epilepsy treatments.
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Affiliation(s)
- Rong Yan
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Linhai Zhang
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Ya Chen
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Yongsu Zheng
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Ping Xu
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
| | - Zucai Xu
- Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China; Key Laboratory of Brain Function and Brain Disease Prevention and Treatment of Guizhou Province, Zunyi, China.
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2
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Iqbal A, Bokhari SFH, Rehman MU, Faizan Sattar SM, Bakht D, Dost W, Basit A. Gut-brain connection in schizophrenia: A narrative review. World J Psychiatry 2025; 15:103751. [DOI: 10.5498/wjp.v15.i5.103751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 02/23/2025] [Accepted: 03/31/2025] [Indexed: 04/30/2025] Open
Abstract
Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive, emotional, and behavioral impairments. The microbiota-gut-brain axis is crucial in its pathophysiology, mediating communication between the gut and brain through neural, immune, endocrine, and metabolic pathways. Dysbiosis, or an imbalance in gut microbiota, is linked to neuroinflammation, systemic inflammation, and neurotransmitter disruptions, all of which contribute to the symptoms of schizophrenia. Gut microbiota-derived metabolites, such as short-chain fatty acids, influence brain function, including immune responses and neurotransmitter synthesis. These findings suggest that microbial imbalances exacerbate schizophrenia, providing a novel perspective on the disorder’s underlying mechanisms. Emerging microbiota-targeted therapies—such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation—show promise as adjunctive treatments, aiming to restore microbial balance and improve clinical outcomes. While further research is needed, targeting the microbiota-gut-brain axis offers an innovative approach to schizophrenia management, with the potential to enhance patient outcomes and quality of life.
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Affiliation(s)
- Asma Iqbal
- Department of Medicine and Surgery, King Edward Medical University, Lahore 54000, Punjab, Pakistan
| | | | - Muneeb Ur Rehman
- Department of Medicine and Surgery, King Edward Medical University, Lahore 54000, Punjab, Pakistan
| | | | - Danyal Bakht
- Department of Medicine and Surgery, King Edward Medical University, Lahore 54000, Punjab, Pakistan
| | - Wahidullah Dost
- Department of Curative Medicine, Kabul University of Medical Sciences, Kabul 10001, Afghanistan
| | - Abdul Basit
- Department of Medicine and Surgery, King Edward Medical University, Lahore 54000, Punjab, Pakistan
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3
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Brandt MJV, van Steenwinckel J, van Emst BL, Lohr J, Mank M, Schipper L, Harvey L, Benders MJNL, de Theije CGM. Human milk oligosaccharides improve white matter and interneuron development in a double-hit rat model for preterm brain injury. Neuropharmacology 2025; 276:110507. [PMID: 40350143 DOI: 10.1016/j.neuropharm.2025.110507] [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: 02/21/2025] [Revised: 04/27/2025] [Accepted: 05/08/2025] [Indexed: 05/14/2025]
Abstract
Mother's own milk is the preferred source of nutrition for preterm infants due to its beneficial compounds, including human milk oligosaccharides (HMOs). HMOs support microbiota and immune development, but their effect on the preterm brain remains unstudied. Here, we examined the therapeutic potential of HMOs and short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a preclinical model for encephalopathy of prematurity. Pregnant Wistar rats were injected with 10 μg/kg lipopolysaccharides at embryonic day 20, and pups were exposed to hypoxia (8% O2, 140 min) at postnatal day (P)4 (fetal inflammation and postnatal hypoxia; FIPH). From P1, FIPH-pups of both sexes were treated intragastrically with HMOs, scGOS/lcFOS (9:1), or water. Transcriptomic analysis of CD11b/c + microglia was performed at P6, while immunohistochemical, microbial and short-chain fatty acid (SCFA) analyses were performed at P20. Decreased cortical myelin in FIPH animals was rescued exclusively by HMOs. Furthermore, both HMOs and scGOS/lcFOS treatments normalized reduced parvalbumin+ interneuron numbers in the hippocampus, potentially through promoting beneficial bacteria, including Lactobacillus and Bifidobacterium, and cecal acetic acid content. Interestingly, treatment with HMOs more effectively restored FIPH-induced upregulation of microglial genes associated with immune activation and normalized persistent activated microglial morphology in FIPH-males. HMOs supplementation holds promise to improve neurodevelopmental outcomes following preterm birth.
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Affiliation(s)
- Myrna J V Brandt
- Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Lundlaan 6, 3584 EA, Utrecht, the Netherlands.
| | - Juliette van Steenwinckel
- Université Paris Cité, Inserm, NeuroDiderot, FHU Prem'impact, 48 Bd Sérurier, F-75019, Paris, France.
| | - Bobbie-Louise van Emst
- Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Lundlaan 6, 3584 EA, Utrecht, the Netherlands.
| | - Julia Lohr
- Danone Research and Innovation, Uppsalalaan 12, 3584 HD, Utrecht, the Netherlands.
| | - Marko Mank
- Danone Research and Innovation, Uppsalalaan 12, 3584 HD, Utrecht, the Netherlands.
| | - Lidewij Schipper
- Danone Research and Innovation, Uppsalalaan 12, 3584 HD, Utrecht, the Netherlands.
| | - Louise Harvey
- Danone Research and Innovation, Uppsalalaan 12, 3584 HD, Utrecht, the Netherlands.
| | - Manon J N L Benders
- Department of Neonatology, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Lundlaan 6, 3584 EA, Utrecht, the Netherlands
| | - Caroline G M de Theije
- Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Lundlaan 6, 3584 EA, Utrecht, the Netherlands.
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4
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Nakagawa Y, Yamada S. Novel hypothesis and therapeutic interventions for irritable bowel syndrome: interplay between metal dyshomeostasis, gastrointestinal dysfunction, and neuropsychiatric symptoms. Mol Cell Biochem 2025; 480:2661-2676. [PMID: 39503802 DOI: 10.1007/s11010-024-05153-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 10/26/2024] [Indexed: 05/03/2025]
Abstract
Irritable bowel syndrome is a gastrointestinal disorder due to multiple pathologies. While patients with this condition experience anxiety and depressed mood more frequently than healthy individuals, it is unclear how gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data suggest that irritable bowel syndrome patients predominantly display a lower zinc intake, which presumably impairs enterochromaffin cells producing 5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and barrier system in the intestine, with the accompanying constipation, diarrhea, low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and zinc concentrations as well as elevated pro-inflammatory cytokine levels in the blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus coeruleus neuroinflammation and hyperactivation with resultant amygdalar overactivation and dorsolateral prefrontal cortex hypoactivation as found in neuropsychiatric disorders. The dysregulation between the dorsolateral prefrontal cortex and amygdala is likely responsible for visceral pain-related anxiety, depressed mood caused by anticipatory anxiety, and visceral pain catastrophizing due to catastrophic thinking or cognitive distortion. Collectively, these events can result in a spiral of gastrointestinal symptoms and neuropsychiatric signs, prompting the progression of irritable bowel syndrome. Given that the negative feedback mechanism in regulation of the hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric cases, dorsolateral prefrontal cortex abnormality accompanied by neuropsychiatric symptoms may be a more significant contributing factor in brain-gut axis malfunction than activation of the hypothalamic corticotropin-releasing hormone system. The proposed mechanistic model could predict novel therapeutic interventions for comorbid irritable bowel syndrome and neuropsychiatric disorders.
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Affiliation(s)
- Yutaka Nakagawa
- Center for Pharma-Food Research (CPFR), Division of Pharmaceutical Sciences, Graduate School of Integrative Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka, 422-8526, Japan.
| | - Shizuo Yamada
- Center for Pharma-Food Research (CPFR), Division of Pharmaceutical Sciences, Graduate School of Integrative Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka, 422-8526, Japan
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Da Motta SAB, Furlani NR, Lourenço AC, Junior SXS, Rezende JCR, Hannas MI. SID Trp-Lys Ratio on Pig Performance and Immune Response After LPS Challenge. Animals (Basel) 2025; 15:1194. [PMID: 40362009 PMCID: PMC12071063 DOI: 10.3390/ani15091194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/10/2025] [Accepted: 03/17/2025] [Indexed: 05/15/2025] Open
Abstract
This study aimed to evaluate the effects of the standardized ileal digestible tryptophan-to-lysine (SID Trp-Lys) ratio through the supplementation of different levels of L-tryptophan on pig performance and immune response following an LPS challenge. A total of 120 entire male pigs, with an average body weight of 16.5 ± 0.50 kg, were allocated in a randomized block design with four treatments, ten replicates per treatment, and three animals per experimental unit. The experimental treatments consisted of SID Trp-Lys ratios of 16%, 18%, 21%, and 24%, achieved through L-tryptophan supplementation. The evaluated performance parameters included the final body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR). Blood samples were collected on day 21 to determine serum serotonin levels, and on day 26, pigs were inoculated with LPS to induce an immune challenge, followed by blood sampling to assess cytokine responses. The results showed that pigs fed the 16% SID Trp-Lys ratio exhibited a lower FBW (p < 0.05). The SID Trp-Lys ratios influenced performance parameters, with quadratic responses (p < 0.05) observed for the FBW and FCR, where the highest FBW and lowest FCR were recorded at 22.05% and 21% SID Trp-Lys, respectively. A linear increase (p < 0.05) was observed for ADG, with a trend for a linear increase (p = 0.056) in ADFI. No effects (p > 0.10) of the SID Trp-Lys ratios were detected on serum serotonin levels. An increase in cytokine levels (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, and TNF-α) was observed in pigs challenged with LPS (p < 0.10) compared to non-challenged animals. An interaction effect (p < 0.10) was detected for IL-2 and IL-18. SID Trp-Lys ratios between 21% and 24% optimize growth performance in pigs from 16 to 33 kg and modulate the immune response under LPS-induced challenge conditions.
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Affiliation(s)
- Stephane Alverina Briguente Da Motta
- Department of Animal Science, Federal University of Viçosa, Viçosa 36570-900, Minas Gerais, Brazil; (S.A.B.D.M.); (N.R.F.); (A.C.L.); (S.X.S.J.)
| | - Nathana Rudio Furlani
- Department of Animal Science, Federal University of Viçosa, Viçosa 36570-900, Minas Gerais, Brazil; (S.A.B.D.M.); (N.R.F.); (A.C.L.); (S.X.S.J.)
| | - Antonio Carlos Lourenço
- Department of Animal Science, Federal University of Viçosa, Viçosa 36570-900, Minas Gerais, Brazil; (S.A.B.D.M.); (N.R.F.); (A.C.L.); (S.X.S.J.)
| | - Sergio Xavier Silva Junior
- Department of Animal Science, Federal University of Viçosa, Viçosa 36570-900, Minas Gerais, Brazil; (S.A.B.D.M.); (N.R.F.); (A.C.L.); (S.X.S.J.)
| | | | - Melissa Izabel Hannas
- Department of Animal Science, Federal University of Viçosa, Viçosa 36570-900, Minas Gerais, Brazil; (S.A.B.D.M.); (N.R.F.); (A.C.L.); (S.X.S.J.)
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6
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Fang Z, Chang S, Niu P, Wang C, Zhang J. Multidimensional-based exploration of gut microbial and metabolite differences in patients with recurrent stroke. Neuroscience 2025; 572:35-48. [PMID: 39914520 DOI: 10.1016/j.neuroscience.2025.02.004] [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: 01/17/2025] [Accepted: 02/02/2025] [Indexed: 03/11/2025]
Abstract
This study aims to explore the differences in gut microbes and their metabolites between patients with original and recurrent stroke, providing insights and justification for the diagnosis and prevention of ischemic stroke progression from the perspective of the gut microbiota-metabolite-brain axis. In this study, fecal samples were collected from patients with Original stroke (Os) and patients with Recurrent stroke (Rs) to assess differences in gut microbiota and to screen for different metabolites that reveal the physiological changes related to the recurrent of ischemic stroke. The results found that there was no significant change in Alpha diversity between the two groups. Beta diversity analysis revealed slight changes in community composition between two groups (Bray-Curtis), although their overall microbial abundance may not have changed (UniFrac). Compared with Os patients, Prevotella, Lachnospiraceae_UCG-010, Holdemanella, and Coprococcus were significantly depleted in the Rs group. Correlation analysis showed that the risk of stroke recurrence was negatively correlated with Lachnospiraceae_UCG-010. In Rs group, metabolites such as carbohydrates and terpene lactones were up-regulated, while those of sesquiterpenoids, triterpenoids, and fatty acids and their couplings were down-regulated. These metabolites are significantly enriched in the pathways of arachidonic acid metabolism, betaine biosynthesis, and linoleic acid metabolism. Compared with the Os, Rs was mainly characterized by minor destruction of anaerobic bacteria and significant depletion of SCFAs-producing bacteria. In addition, the related compounds involved in arachidonic acid metabolism and linoleic acid metabolism pathway may be associated with the progression of ischemic stroke.
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Affiliation(s)
- Zongwei Fang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Sijie Chang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Peiguang Niu
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Chunhua Wang
- Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jinhua Zhang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
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7
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Crain E, Minaya DM, de La Serre CB. Microbiota-induced inflammation mediates the impacts of a Western diet on hippocampal-dependent memory. Nutr Res 2025; 138:89-106. [PMID: 40339190 DOI: 10.1016/j.nutres.2025.04.002] [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: 05/13/2024] [Revised: 04/01/2025] [Accepted: 04/01/2025] [Indexed: 05/10/2025]
Abstract
Obesity is associated with impaired hippocampal-dependent memory, but the mechanisms driving this pathology are not fully understood. Western diets (WD) contribute to obesity, and previous reviews have described a role for WD in impaired hippocampal-dependent memory. However, there is need for a more detailed description of the pathways by which WD may impair memory. The short vs long-term effect of specific dietary components on brain structure and functions as well as the precise mechanism and molecular pathways involved are still not fully understood. This review focuses on the mechanisms and effects of gut microbiota-driven neuroinflammation. WD leads to changes and imbalance in bacterial taxa abundances that are deleterious to the host health (gut dysbiosis) and studies in rodent models show these changes are sufficient to impair hippocampal-dependent memory. Here, we discuss a variety of proposed mechanisms linking microbiota composition to hippocampal function, with a focus on neuroinflammation. Gut microbiota impacts gastrointestinal barrier function, leading to increased circulating proinflammatory bacterial products, increased blood-brain barrier permeability, and neuroinflammation.
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Affiliation(s)
- Eden Crain
- Department of Nutritional Sciences, University of Georgia, Athens, GA, USA
| | - Dulce M Minaya
- Department of Nutritional Sciences, University of Georgia, Athens, GA, USA
| | - Claire B de La Serre
- Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
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8
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Wei S, Ma X, Chen Y, Wang J, Hu L, Liu Z, Mo L, Zhou N, Chen W, Zhu H, Yan S. Alzheimer's Disease-Derived Outer Membrane Vesicles Exacerbate Cognitive Dysfunction, Modulate the Gut Microbiome, and Increase Neuroinflammation and Amyloid-β Production. Mol Neurobiol 2025; 62:5109-5132. [PMID: 39514171 DOI: 10.1007/s12035-024-04579-6] [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: 06/16/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024]
Abstract
Although our understanding of the molecular biology of Alzheimer's disease (AD) continues to improve, the etiology of the disease, particularly the involvement of gut microbiota disturbances, remains a challenge. Outer membrane vesicles (OMVs) play a key role in central nervous system diseases, but the impact of OMVs on AD progression remains unclear. In this study, we hypothesized that AD-derived OMVs (OMVsAD) were a risk factor in AD pathology. To test our hypothesis, young APP/PS1 mice (AD mice) were given OMVsAD by gavage. Young AD mice were euthanized 120 days after gavage to assess the intestinal barrier, gut microbiota diversity, mediators of neuroinflammation, glial markers, amyloid burden, and short-chain fatty acid (SCFA) levels. Our results showed that OMVsAD accelerated cognitive dysfunction after 120 days of intragastric administration. Morris water maze experiment and new object recognition test showed that OMVsAD caused significantly poorer spatial ability learning and memory of the AD mice. We observed the OMVsAD-treated APP/PS1 mice display OMVs disrupting the intestinal barrier compared with controls of normal human-derived OMVs. Compared with the OMVsHC group, claudin-5 and ZO-1 related to the intestinal barrier were significantly downregulated in the OMVsAD group. The OMVsAD activate microglia in the cerebral cortex and hippocampus of AD mice, and the levels of IL-1β, IL-6, TNF-α, and NF-Κb were upregulated. We also found that OMVsAD increased Aβ production. 16S rRNA sequencing showed that OMVsAD negatively regulated the α- and β-diversity index of intestinal flora and reduced the levels of SCFA. OMVsAD may change the intestinal flora of young AD, damage the intestinal mucosa and blood-brain barrier, and accelerate AD neuropathological damage.
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Affiliation(s)
- Shouchao Wei
- The Third Department of Neurology, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
- Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
| | - Xiaochen Ma
- The Third Department of Neurology, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
- Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
| | - Yating Chen
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Junjun Wang
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- Basic Medicine College, Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Li Hu
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- Basic Medicine College, Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Zhou Liu
- Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Lang Mo
- The Third Department of Neurology, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
| | - Ning Zhou
- The Third Department of Neurology, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
- Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
| | - Wenrong Chen
- The Third Department of Neurology, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China
| | - He Zhu
- Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China.
| | - Shian Yan
- The Third Department of Neurology, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China.
- Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong, China.
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Li Q, Xie Y, Lin J, Li M, Gu Z, Xin T, Zhang Y, Lu Q, Guo Y, Xing Y, Wang W. Microglia Sing the Prelude of Neuroinflammation-Associated Depression. Mol Neurobiol 2025; 62:5311-5332. [PMID: 39535682 DOI: 10.1007/s12035-024-04575-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
Major depressive disorder (MDD) is a psychiatric condition characterized by sadness and anhedonia and is closely linked to chronic low-grade neuroinflammation, which is primarily induced by microglia. Nonetheless, the mechanisms by which microglia elicit depressive symptoms remain uncertain. This review focuses on the mechanism linking microglia and depression encompassing the breakdown of the blood-brain barrier, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, the vagus and sympathetic nervous systems, and the susceptibility influenced by epigenetic modifications on microglia. These pathways may lead to the alterations of microglia in cytokine levels, as well as increased oxidative stress. Simultaneously, many antidepressant treatments can alter the immune phenotype of microglia, while anti-inflammatory treatments can also have antidepressant effects. This framework linking microglia, neuroinflammation, and depression could serve as a reference for targeting microglia to treat depression.
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Affiliation(s)
- Qingqing Li
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Ying Xie
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Jinyi Lin
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Miaomiao Li
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Ziyan Gu
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Tianli Xin
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Yang Zhang
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Qixia Lu
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Yihui Guo
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China
| | - Yanhong Xing
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
| | - Wuyang Wang
- Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
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Saadh MJ, Ahmed HH, Kareem RA, Sanghvi G, Ganesan S, Agarwal M, Kaur P, Taher WM, Alwan M, Jawad MJ, Hamad AK. Short-chain fatty acids in Huntington's disease: Mechanisms of action and their therapeutic implications. Pharmacol Biochem Behav 2025; 249:173972. [PMID: 39983928 DOI: 10.1016/j.pbb.2025.173972] [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: 12/03/2024] [Revised: 02/10/2025] [Accepted: 02/14/2025] [Indexed: 02/23/2025]
Abstract
Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and emotional instability, primarily resulting from the abnormal accumulation of mutant huntingtin protein. Growing research highlights the role of intestinal microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), in modulating HD progression. SCFAs, including acetate, propionate, and butyrate, are produced by gut bacteria through dietary fiber fermentation and are recognized for their neuroprotective properties. Evidence suggests that SCFAs regulate neuroinflammation, neuronal communication, and metabolic functions within the central nervous system (CNS). In HD, these compounds may support neuronal health, reduce oxidative stress, and enhance blood-brain barrier (BBB) integrity. Their mechanisms of action involve binding to G-protein-coupled receptors (GPCRs) and modulating gene expression through epigenetic pathways, underscoring their therapeutic potential. This analysis examines the significance of SCFAs in HD, emphasizing the gut-brain axis and the benefits of dietary interventions aimed at modifying gut microbiota composition and promoting SCFA production. Further research into these pathways may pave the way for novel HD management strategies and improved therapeutic outcomes.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan.
| | | | | | - Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot 360003, Gujarat, India
| | - Subbulakshmi Ganesan
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Mohit Agarwal
- Department of Pharmaceutical Chemistry, NIMS Institute of Pharmacy, NIMS University, Rajasthan, Jaipur,302131, India
| | - Parjinder Kaur
- Chandigarh Pharmacy College, Chandigarh Group of Colleges-Jhanjeri, Mohali 140307, Punjab, India
| | - Waam Mohammed Taher
- College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
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11
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Zhu B, Gu Z, Hu H, Huang J, Zeng Z, Liang H, Yuan Z, Huang S, Qiu Y, Sun XD, Liu Y. Altered Gut Microbiota Contributes to Acute-Respiratory-Distress-Syndrome-Related Depression through Microglial Neuroinflammation. RESEARCH (WASHINGTON, D.C.) 2025; 8:0636. [PMID: 40110391 PMCID: PMC11919824 DOI: 10.34133/research.0636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 03/22/2025]
Abstract
Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria-Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite-propionic acid-alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.
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Affiliation(s)
- Bowen Zhu
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
- Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Zheng Gu
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
- Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Hongbin Hu
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jie Huang
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
- Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Zhenhua Zeng
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Haoxuan Liang
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Ziyi Yuan
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Shiwei Huang
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Yuetan Qiu
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Xiang-Dong Sun
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
- Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Youtan Liu
- Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
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12
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Ma P, Sun W, Sun C, Tan J, Dong X, He J, Ali A, Chen M, Zhang L, Wu L, Wang P. Using gut microbiota and non-targeted metabolomics techniques to study the effect of xylitol on alleviating DSS-induced inflammatory bowel disease in mice. BMC Immunol 2025; 26:18. [PMID: 40065221 PMCID: PMC11892251 DOI: 10.1186/s12865-025-00700-z] [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: 10/04/2024] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) has become a global healthcare issue, with its incidence continuing to rise, but currently there is no complete cure. Xylitol is a widely used sweetener in various foods and beverages, but there is limited research on the effects of xylitol on IBD symptoms. AIM Study on the effect of oral xylitol in improving intestinal inflammation and damage in IBD mice, further explore the mechanism of xylitol in alleviating IBD symptoms using intestinal microbiota and non-targeted metabolomics techniques. METHODS An IBD mouse model was induced using sodium dextran sulfate (DSS). After 30 days of oral administration of xylitol, we assessed the disease activity index (DAI) scores of mice in each group. The expression levels of inflammatory factors in the colon tissues were measured using qPCR. Additionally, we examined the damage to the intestinal mucosa and tight junction structures through HE staining and immunohistochemical staining. Finally, the alterations in the gut microbiota of the mice were analyzed using 16S rDNA sequencing technology.The production of three main short-chain fatty acids (SCFAs, including acetate, propionic acid and butyric acid) in feces and the changes of serum metabolomics were measured by non-targeted metabolomics techniques. RESULTS The findings indicated that xylitol effectively mitigated weight loss and improved the DAI score in mice with IBD. Moreover, xylitol reduced the expressions of Caspase-1, IL-1β, and TNF-α in the colon tissue of the mice, and increased the expressions of ZO-1 and occludin in intestinal mucosal. Xylitol could enhance the variety of intestinal bacteria in IBD mice and influenced the abundance of different bacterial species. Additionally, metabolomic analysis revealed that oral xylitol increased the levels of three main SCFAs in the feces of IBD mice, while also impacting serum metabolites. CONCLUSIONS Our findings suggest that xylitol can help improve IBD symptoms. Xylitol can improve the intestinal flora of IBD mice and increase the production of SCFAs to play an anti-inflammatory role and protect the mucosal tight junction barrier. These discoveries present a fresh prophylactic treatment of IBD. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Peng Ma
- Department of Anesthesiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, China
| | - Wen Sun
- Department of Critical Care Medicine, Jurong Hospital Afliated to Jiangsu University, Zhenjiang, Jiangsu, 212400, China
| | - Chang Sun
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Jiajun Tan
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Xueyun Dong
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Jiayuan He
- Health Testing Center, Zhenjiang Center for Disease Control and Prevention, Zhenjiang, 212002, China
| | - Asmaa Ali
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
- Department of Pulmonary Medicine, Abbassia Chest Hospital, EMOH, Cairo, 11517, Egypt
| | - Min Chen
- Public Experiment and Service Center, Jiangsu University, Zhenjiang, 212013, China
| | - Leilei Zhang
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China
| | - Liang Wu
- Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, 212013, China.
- Department of Laboratory Medicine, Taizhou Second People's Hospital, Taizhou, 225309, China.
| | - Pingping Wang
- Department of Laboratory Medicine, Taizhou Second People's Hospital, Taizhou, 225309, China.
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13
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Chen Q, Wang X, Zhang P, Li B. Recent trends in human milk oligosaccharides: New synthesis technology, regulatory effects, and mechanisms of non-intestinal functions. Compr Rev Food Sci Food Saf 2025; 24:e70147. [PMID: 40091651 DOI: 10.1111/1541-4337.70147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 03/19/2025]
Abstract
Recently, the non-intestinal functions of human milk oligosaccharides (HMOs) have been widely documented, including their roles in promoting brain development and growth, as well as ameliorating anxiety, allergies, and obesity. Understanding their mechanisms of action is becoming increasingly critical. Furthermore, these effects are frequently associated with the type and structure of HMOs. As an innovative technology, "plant factory" is expected to complement traditional synthesis technology. This study reviews the novel "plant factory" synthesis techniques. Particular emphasis is placed on the processes, advantages, and limitations of "plant factory" synthesis of HMOs. This technology can express genes related to HMO synthesis instantaneously in plant leaves, thereby enabling the rapid and cost-effective generation of HMOs. However, "plant factory" technology remains underdeveloped, and challenges related to low yield and unsustainable production must be addressed. Furthermore, we present an overview of the most recent clinical and preclinical studies on the non-intestinal functions of HMOs. This review emphasizes the mechanisms of action underlying the non-intestinal functions of HMOs. HMOs primarily exert non-intestinal functions through the cleavage of beneficial monomer components, metabolism to produce advantageous metabolites, and regulation of immune responses.
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Affiliation(s)
- Qingxue Chen
- Food College, Northeast Agricultural University, Harbin, China
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Xiangxin Wang
- Food College, Northeast Agricultural University, Harbin, China
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Peng Zhang
- Food College, Northeast Agricultural University, Harbin, China
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
| | - Bailiang Li
- Food College, Northeast Agricultural University, Harbin, China
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, China
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14
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Schumacher SM, Doyle WJ, Hill K, Ochoa-Repáraz J. Gut microbiota in multiple sclerosis and animal models. FEBS J 2025; 292:1330-1356. [PMID: 38817090 PMCID: PMC11607183 DOI: 10.1111/febs.17161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 04/15/2024] [Accepted: 05/10/2024] [Indexed: 06/01/2024]
Abstract
Multiple sclerosis (MS) is a chronic central nervous system (CNS) neurodegenerative and neuroinflammatory disease marked by a host immune reaction that targets and destroys the neuronal myelin sheath. MS and correlating animal disease models show comorbidities, including intestinal barrier disruption and alterations of the commensal microbiome. It is accepted that diet plays a crucial role in shaping the microbiota composition and overall gastrointestinal (GI) tract health, suggesting an interplay between nutrition and neuroinflammation via the gut-brain axis. Unfortunately, poor host health and diet lead to microbiota modifications that could lead to significant responses in the host, including inflammation and neurobehavioral changes. Beneficial microbial metabolites are essential for host homeostasis and inflammation control. This review will highlight the importance of the gut microbiota in the context of host inflammatory responses in MS and MS animal models. Additionally, microbial community restoration and how it affects MS and GI barrier integrity will be discussed.
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Affiliation(s)
| | | | - Kristina Hill
- Department of Biological Sciences, Boise State University, Boise, ID 83725
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15
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Sullivan O, Sie C, Ng KM, Cotton S, Rosete C, Hamden JE, Singh AP, Lee K, Choudhary J, Kim J, Yu H, Clayton CA, Carranza Garcia NA, Voznyuk K, Deng BD, Plett N, Arora S, Ghezzi H, Huan T, Soma KK, Yu JPJ, Tropini C, Ciernia AV. Early-life gut inflammation drives sex-dependent shifts in the microbiome-endocrine-brain axis. Brain Behav Immun 2025; 125:117-139. [PMID: 39674560 DOI: 10.1016/j.bbi.2024.12.003] [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: 05/23/2024] [Revised: 11/13/2024] [Accepted: 12/09/2024] [Indexed: 12/16/2024] Open
Abstract
Despite recent advances in understanding the connection between the gut microbiota and the adult brain, significant knowledge gaps remain regarding how gut inflammation affects brain development. We hypothesized that gut inflammation during early life would negatively affect neurodevelopment by disrupting microbiota communication to the brain. We therefore developed a novel pediatric chemical model of inflammatory bowel disease (IBD), an incurable condition affecting millions of people worldwide. IBD is characterized by chronic intestinal inflammation, and is associated with comorbid symptoms such as anxiety, depression and cognitive impairment. Notably, 25% of patients with IBD are diagnosed during childhood, and the effects of chronic inflammation during this critical developmental period remain poorly understood. This study investigated the effects of early-life gut inflammation induced by DSS (dextran sulfate sodium) on a range of microbiota, endocrine, and behavioral outcomes, focusing on sex-specific impacts. DSS-treated mice exhibited increased intestinal inflammation and altered microbiota membership, which correlated with changes in microbiota-derived circulating metabolites. The majority of behavioral measures were unaffected, with the exception of impaired mate-seeking behaviors in DSS-treated males. DSS-treated males also showed significantly smaller seminal vesicles, lower circulating androgens, and decreased intestinal hormone-activating enzyme activity compared to vehicle controls. In the brain, DSS treatment led to chronic, sex-specific alterations in microglial morphology. These results suggest that early-life gut inflammation causes changes in gut microbiota composition, affecting short-chain fatty acid (SCFA) producers and glucuronidase (GUS) activity, correlating with altered SCFA and androgen levels. The findings highlight the developmental sensitivity to inflammation-induced changes in endocrine signalling and emphasize the long-lasting physiological and microbiome changes associated with juvenile IBD.
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Affiliation(s)
- Olivia Sullivan
- Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
| | - Claire Sie
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada
| | - Katharine M Ng
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada
| | - Sophie Cotton
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada
| | - Cal Rosete
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
| | - Jordan E Hamden
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
| | - Ajay Paul Singh
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Kristen Lee
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
| | - Jatin Choudhary
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
| | - Jennifer Kim
- Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
| | - Huaxu Yu
- Department of Chemistry, University of British Columbia, Vancouver, Canada
| | - Charlotte A Clayton
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada
| | | | - Kateryna Voznyuk
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
| | - Brian D Deng
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada
| | - Nadine Plett
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
| | - Sana Arora
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
| | - Hans Ghezzi
- Department of Bioinformatics, University of British Columbia, Vancouver, Canada
| | - Tao Huan
- Department of Chemistry, University of British Columbia, Vancouver, Canada
| | - Kiran K Soma
- Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Psychology, University of British Columbia, Vancouver Canada
| | - John-Paul J Yu
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Carolina Tropini
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, Canada; Humans and the Microbiome Program, Canadian Institute for Advanced Research (CIFAR), Toronto, Canada.
| | - Annie Vogel Ciernia
- Graduate Program in Neuroscience, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
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16
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Ameen AO, Nielsen SW, Kjær MW, Andersen JV, Westi EW, Freude KK, Aldana BI. Metabolic preferences of astrocytes: Functional metabolic mapping reveals butyrate outcompetes acetate. J Cereb Blood Flow Metab 2025; 45:528-541. [PMID: 39340267 PMCID: PMC11563520 DOI: 10.1177/0271678x241270457] [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: 03/19/2024] [Revised: 06/11/2024] [Accepted: 07/02/2024] [Indexed: 09/30/2024]
Abstract
Disruptions to the gut-brain-axis have been linked to neurodegenerative disorders. Of these disruptions, reductions in the levels of short-chain fatty acids (SCFAs), like butyrate, have been observed in mouse models of Alzheimer's disease (AD). Butyrate supplementation in mice has shown promise in reducing neuroinflammation, amyloid-β accumulation, and enhancing memory. However, the underlying mechanisms remain unclear. To address this, we investigated the impact of butyrate on energy metabolism in mouse brain slices, primary cultures of astrocytes and neurons and in-vivo by dynamic isotope labelling with [U-13C]butyrate and [1,2-13C]acetate to map metabolism via mass spectrometry. Metabolic competition assays in cerebral cortical slices revealed no competition between butyrate and the ketone body, β-hydroxybutyrate, but competition with acetate. Astrocytes favoured butyrate metabolism compared to neurons, suggesting that the astrocytic compartment is the primary site of butyrate metabolism. In-vivo metabolism investigated in the 5xFAD mouse, an AD pathology model, showed no difference in 13C-labelling of TCA cycle metabolites between wild-type and 5xFAD brains, but butyrate metabolism remained elevated compared to acetate in both groups, indicating sustained uptake and metabolism in 5xFAD mice. Overall, these findings highlight the role of astrocytes in butyrate metabolism and the potential use of butyrate as an alternative brain fuel source.
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Affiliation(s)
- Aishat O Ameen
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Sebastian W Nielsen
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Martin W Kjær
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens V Andersen
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Emil W Westi
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Kristine K Freude
- Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
| | - Blanca I Aldana
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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17
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Tang Y, Zhang Y, Chen C, Cao Y, Wang Q, Tang C. Gut microbiota: A new window for the prevention and treatment of neuropsychiatric disease. J Cent Nerv Syst Dis 2025; 17:11795735251322450. [PMID: 39989718 PMCID: PMC11846125 DOI: 10.1177/11795735251322450] [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: 10/17/2024] [Revised: 12/11/2024] [Accepted: 01/27/2025] [Indexed: 02/25/2025] Open
Abstract
Under normal physiological conditions, gut microbiota and host mutually coexist. They play key roles in maintaining intestinal barrier integrity, absorption, and metabolism, as well as promoting the development of the central nervous system (CNS) and emotional regulation. The dysregulation of gut microbiota homeostasis has attracted significant research interest, specifically in its impact on neurological and psychiatric disorders. Recent studies have highlighted the important role of the gut- brain axis in conditions including Alzheimer's Disease (AD), Parkinson's Disease (PD), and depression. This review aims to elucidate the regulatory mechanisms by which gut microbiota affect the progression of CNS disorders via the gut-brain axis. Additionally, we discuss the current research landscape, identify gaps, and propose future directions for microbial interventions against these diseases. Finally, we provide a theoretical reference for clinical treatment strategies and drug development for AD, PD, and depression.
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Affiliation(s)
- Yali Tang
- Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yizhu Zhang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
| | - Chen Chen
- Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Ying Cao
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of China
| | - Qiaona Wang
- School of Ecology and Applied Meteorology, Nanjing University of Information Science & Technology, Nanjing, People’s Republic of China
| | - Chuanfeng Tang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China
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18
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Peña-Durán E, García-Galindo JJ, López-Murillo LD, Huerta-Huerta A, Balleza-Alejandri LR, Beltrán-Ramírez A, Anaya-Ambriz EJ, Suárez-Rico DO. Microbiota and Inflammatory Markers: A Review of Their Interplay, Clinical Implications, and Metabolic Disorders. Int J Mol Sci 2025; 26:1773. [PMID: 40004236 PMCID: PMC11854938 DOI: 10.3390/ijms26041773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/12/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025] Open
Abstract
The human microbiota, a complex ecosystem of microorganisms, plays a pivotal role in regulating host immunity and metabolism. This review investigates the interplay between microbiota and inflammatory markers, emphasizing their impact on metabolic and autoimmune disorders. Key inflammatory biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6), lipopolysaccharides (LPS), zonulin (ZO-1), and netrin-1 (Ntn1), are discussed in the context of intestinal barrier integrity and chronic inflammation. Dysbiosis, characterized by alterations in microbial composition and function, directly modulates the levels and activity of these biomarkers, exacerbating inflammatory responses and compromising epithelial barriers. The disruption of microbiota is further correlated with increased intestinal permeability and chronic inflammation, serving as a precursor to conditions like type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease. Additionally, this review examines therapeutic strategies, including probiotics and prebiotics, designed to restore microbial balance, mitigate inflammation, and enhance metabolic homeostasis. Emerging evidence positions microbiota-targeted interventions as critical components in the advancement of precision medicine, offering promising avenues for diagnosing and treating inflammatory and metabolic disorders.
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Affiliation(s)
- Emiliano Peña-Durán
- Licenciatura en Médico Cirujano y Partero, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico
| | - Jesús Jonathan García-Galindo
- Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Calle Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Mexico
- Departamento Académico Aparatos y Sistemas II, Decanato de Ciencias de la Salud, Universidad Autónoma de Guadalajara, Zapopan 44670, Mexico
| | - Luis Daniel López-Murillo
- Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Calle Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Mexico
- Departamento Académico Aparatos y Sistemas I, Decanato de Ciencias de la Salud, Universidad Autónoma de Guadalajara, Zapopan 44670, Mexico
| | - Alfredo Huerta-Huerta
- Hospital Medica de la Ciudad, Santa Catalina, Calle. Pablo Valdez 719, La Perla, Guadalajara 44360, Mexico
| | - Luis Ricardo Balleza-Alejandri
- Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico
| | - Alberto Beltrán-Ramírez
- Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Calle Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Mexico
- Departamento Académico Aparatos y Sistemas I, Decanato de Ciencias de la Salud, Universidad Autónoma de Guadalajara, Zapopan 44670, Mexico
| | - Elsa Janneth Anaya-Ambriz
- Departamento de Ciencias de la Salud, Centro Universitario de los Valles, Universidad de Guadalajara, Ameca 46708, Mexico
| | - Daniel Osmar Suárez-Rico
- Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Calle Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Mexico
- Departamento Académico Aparatos y Sistemas II, Decanato de Ciencias de la Salud, Universidad Autónoma de Guadalajara, Zapopan 44670, Mexico
- Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e Ingenierías (CUCEI), Universidad de Guadalajara, Guadalajara 44430, Mexico
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Zhang A, Li D, Yu T, Zhang M, Cui Y, Wang H, Dong T, Wu Y. Multi-Omics Approach to Evaluate Effects of Dietary Sodium Butyrate on Antioxidant Capacity, Immune Function and Intestinal Microbiota Composition in Adult Ragdoll Cats. Metabolites 2025; 15:120. [PMID: 39997745 PMCID: PMC11857798 DOI: 10.3390/metabo15020120] [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: 12/21/2024] [Revised: 02/05/2025] [Accepted: 02/07/2025] [Indexed: 02/26/2025] Open
Abstract
OBJECTIVES Sodium butyrate (SB) is a typical postbiotic known to positively affect economic animals in recent years, but research on SB in pet cats is scarce. Consequently, this study sought to explore the influence of SB on anti-inflammatory and antioxidant capacity, immune function, and gut microbiota of adult cats through the assessment of biochemical parameters and comprehensive integrative omics analysis. METHODS A total of 30 adult cats were divided into three groups: a basal diet (NC), basal diet with 0.05% SB (SB5), and basal diet with 0.1% SB (SB10). The experiment lasted for 6 weeks. RESULTS The results indicated that the fecal level of calprotectin was lower in the SB10 group than in the SB5 and NC groups. The SB10 group reduced the serum levels of TNF-α, IL-1β and DAO compared with the NC group (p < 0.05). In addition, the SB10 diet increased the GSH-Px level and decreased MDA content compared with the NC diet (p < 0.05). Transcriptomic analysis showed that the gene expression of VCAM1 exhibited a notable decrease in the SB10 group compared to the NC group (p < 0.05). The analysis of gut microbiota revealed that the richness of gut microbiota was higher in the SB10 than in the NC group (p < 0.05), and the abundance of Lachnospiraceae, Lachnoclostridium, Blautia, and Roseburia was greater in the SB10 than in the NC group (p < 0.05). CONCLUSIONS Dietary SB could enhance the antioxidant and anti-inflammatory capacity, improve immune function, and positively regulate the gut microbiota composition in adult cats.
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Affiliation(s)
- Anxuan Zhang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (A.Z.); (T.Y.); (M.Z.); (Y.C.); (H.W.); (T.D.)
| | - Deping Li
- Hangzhou Netease Yanxuan Trading Co., Ltd., Hangzhou 310051, China;
| | - Tong Yu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (A.Z.); (T.Y.); (M.Z.); (Y.C.); (H.W.); (T.D.)
| | - Mingrui Zhang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (A.Z.); (T.Y.); (M.Z.); (Y.C.); (H.W.); (T.D.)
| | - Yingyue Cui
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (A.Z.); (T.Y.); (M.Z.); (Y.C.); (H.W.); (T.D.)
| | - Haotian Wang
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (A.Z.); (T.Y.); (M.Z.); (Y.C.); (H.W.); (T.D.)
| | - Tianyu Dong
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (A.Z.); (T.Y.); (M.Z.); (Y.C.); (H.W.); (T.D.)
| | - Yi Wu
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; (A.Z.); (T.Y.); (M.Z.); (Y.C.); (H.W.); (T.D.)
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20
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Deng J, Li J, Li S, Zhang D, Bai X. Progress of research on short-chain fatty acids, metabolites of gut microbiota, and acute ischemic stroke. Clin Neurol Neurosurg 2025; 249:108725. [PMID: 39805257 DOI: 10.1016/j.clineuro.2025.108725] [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: 11/02/2024] [Revised: 12/28/2024] [Accepted: 01/04/2025] [Indexed: 01/16/2025]
Abstract
Acute ischemic stroke (AIS) significantly impacts the well-being and quality of life of individuals within our population. Short-chain fatty acids (SCFAs), metabolites produced by the intestinal microbiota, are integral to the bidirectional regulatory pathway linking the gut and the brain. SCFAs may significantly influence the risk, prognosis, recurrence, and management of complications associated with AIS. Potential mechanisms underlying these effects include the facilitation of brain-gut barrier repair, the mitigation of oxidative stress, the reduction of neuroinflammatory responses, and the inhibition of autophagy and apoptosis. Consequently, SCFAs hold promise as a prospective target for AIS intervention, with the potential to significantly impact AIS prevention and treatment strategies.
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Affiliation(s)
- Jinbao Deng
- Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China; College of Integration of Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China.
| | - Jianrong Li
- Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China; College of Integration of Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China
| | - Shuangyang Li
- Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China; College of Integration of Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, China
| | - Dechou Zhang
- Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China; College of Integration of Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, China
| | - Xue Bai
- Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China; College of Integration of Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China; Institute of Integrated Chinese and Western Medicine, Southwest Medical University, Luzhou, China.
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21
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Yi C, Huang S, Zhang W, Guo L, Xia T, Huang F, Yan Y, Li H, Yu B. Synergistic interactions between gut microbiota and short chain fatty acids: Pioneering therapeutic frontiers in chronic disease management. Microb Pathog 2025; 199:107231. [PMID: 39681288 DOI: 10.1016/j.micpath.2024.107231] [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: 07/17/2024] [Revised: 12/04/2024] [Accepted: 12/12/2024] [Indexed: 12/18/2024]
Abstract
Microorganisms in the gut play a pivotal role in human health, influencing various pathophysiological processes. Certain microorganisms are particularly essential for maintaining intestinal homeostasis, reducing inflammation, supporting nervous system function, and regulating metabolic processes. Short-chain fatty acids (SCFAs) are a subset of fatty acids produced by the gut microbiota (GM) during the fermentation of indigestible polysaccharides. The interaction between GM and SCFAs is inherently bidirectional: the GM not only shapes SCFAs composition and metabolism but SCFAs also modulate microbiota's diversity, stability, growth, proliferation, and metabolism. Recent research has shown that GM and SCFAs communicate through various pathways, mainly involving mechanisms related to inflammation and immune responses, intestinal barrier function, the gut-brain axis, and metabolic regulation. An imbalance in GM and SCFA homeostasis can lead to the development of several chronic diseases, including inflammatory bowel disease, colorectal cancer, systemic lupus erythematosus, Alzheimer's disease, and type 2 diabetes mellitus. This review explores the synergistic interactions between GM and SCFAs, and how these interactions directly or indirectly influence the onset and progression of various diseases through the regulation of the mechanisms mentioned above.
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Affiliation(s)
- Chunmei Yi
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Shanshan Huang
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Wenlan Zhang
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Lin Guo
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Tong Xia
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Fayin Huang
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Yijing Yan
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Huhu Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Bin Yu
- Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
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Cai R, Zhang J, Song Y, Liu X, Xu H. Research Progress on the Degradation of Human Milk Oligosaccharides (HMOs) by Bifidobacteria. Nutrients 2025; 17:519. [PMID: 39940377 PMCID: PMC11820314 DOI: 10.3390/nu17030519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
The purpose of this study was to investigate the degradation mechanism of Bifidobacterium on breast milk oligosaccharides (HMOs) and its application in infant nutrition. The composition and characteristics of HMOs were introduced, and the degradation mechanism of HMOs by Bifidobacterium was described, including intracellular and extracellular digestion and species-specific differences. The interaction between Bifidobacterium and Bacteroides in the process of degrading HMOs and its effect on intestinal microecology were analyzed. The effects of HMO formula milk powder on the intestinal microbiota of infants were discussed, including simulating breast milk composition, regulating intestinal flora and immune function, infection prevention, and brain development. Finally, the research results are summarized, and future research directions are proposed to provide directions for research in the field of infant nutrition.
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Affiliation(s)
| | | | | | - Xiaoyong Liu
- School of Biological Science and Technology, University of Jinan, Jinan 250024, China; (R.C.); (J.Z.); (Y.S.)
| | - Huilian Xu
- School of Biological Science and Technology, University of Jinan, Jinan 250024, China; (R.C.); (J.Z.); (Y.S.)
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Gao W, Wu X, Wang Y, Lu F, Liu F. Brazilin-Rich Extract from Caesalpinia sappan L. Attenuated the Motor Deficits and Neurodegeneration in MPTP/p-Induced Parkinson's Disease Mice by Regulating Gut Microbiota and Inhibiting Inflammatory Responses. ACS Chem Neurosci 2025; 16:181-194. [PMID: 39711007 DOI: 10.1021/acschemneuro.4c00679] [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] [Indexed: 12/24/2024] Open
Abstract
Parkinson's disease (PD) is a complicated neurological disease with an unclear pathogenesis. However, dysregulation of gut microbiota and inflammation response play crucial roles in the progression of PD. Caesalpinia sappan L., a traditional medicinal plant containing brazilin as its primary active compound, is known for its anti-inflammatory and neuroprotective properties. However, the impact of C. sappan L. extract (SE) on PD through the regulation of the microbiota-gut-brain axis remains unclear. This study investigated the effects and mechanisms of a 91.23% brazilin-enriched SE on MPTP/p-induced PD mice. Results showed that SE significantly ameliorated motor deficits and protected dopaminergic neurons in PD mice. Additionally, SE reduced oxidative stress and inflammation in the brain. SE also restored gut microbiota by increasing Firmicutes and decreasing Bacteroidetes, alongside enhancing the production of short-chain fatty acids (SCFAs) like butyric acid. Furthermore, SE mitigated intestinal barrier damage by enhancing the expression of ZO-1 and occludin, thereby decreasing lipopolysaccharide leakage and inflammatory factor release. Molecular simulations suggested that butyric acid may maintain intestinal integrity by stabilizing ZO-I and occludin conformations. In conclusion, SE exhibited a protective effect on motor deficits and neurodegeneration in PD by regulating gut microbiota and SCFAs, repairing the intestinal barrier, and mitigating inflammatory responses.
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Affiliation(s)
- Wen Gao
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, P. R. China
- Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, P. R. China
- College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China
| | - Xinni Wu
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, P. R. China
- Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, P. R. China
- College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China
| | - Yang Wang
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, P. R. China
- Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, P. R. China
- College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China
| | - Fuping Lu
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, P. R. China
- Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, P. R. China
- College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China
| | - Fufeng Liu
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, P. R. China
- Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, P. R. China
- College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, P. R. China
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Zhao Q, Xu Y, Li X, Chen X. L-shaped association of dietary inflammatory index (DII) and chronic diarrhea: results from NHANES 2005-2010. BMC Public Health 2025; 25:81. [PMID: 39780113 PMCID: PMC11707886 DOI: 10.1186/s12889-025-21292-8] [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: 04/03/2024] [Accepted: 01/02/2025] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Since diet is a known modulator of inflammation, the Dietary Inflammatory Index (DII), which quantifies the inflammatory potential of an individual's diet, becomes a significant parameter to consider. Chronic diarrhea is commonly linked to inflammatory processes within the gut. Thus, this study aimed to explore the potential link between DII and chronic diarrhea. METHODS This research utilized data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. The DII was calculated according to the average intake of 28 nutrients using information gathered from two 24-hour recall interviews. The Bristol Stool Form Scale (BSFS) was adopted to describe chronic diarrhea, identifying stool Type 6 and Type 7. Multivariate logistic regression models examined the causal connection between DII and chronic diarrhea. Additionally, subgroup analyses and interaction tests were conducted. RESULTS The study encompassed 11,219 adults, among whom 7.45% reported chronic diarrhea. Initially, multivariate logistic regression analysis revealed a positive association between DII and chronic diarrhea. Nevertheless, this connection lost statistical significance (OR = 1.00; 95% CI, 0.96-1.05; P = 0.8501) after adjusting for all confounding variables. Stratified by sex, the analysis revealed a notable rise in the risk of chronic diarrhea with increasing DII among female participants (all P for trend < 0.05). This tendency remained constant even after full adjustment (P for trend = 0.0192), whereas no significant association was noted in males (all P for trend > 0.05). Furthermore, an L-shaped association emerged between DII and chronic diarrhea, with an inflection point of -1.34. In the population with DII scores below -1.34, each unit increase in DII correlated with a 27% reduction in the probability of chronic diarrhea (OR = 0.73; 95% CI, 0.57-0.93), whereas in the population with DII scores above -1.34, the risk increased by 4% (OR = 1.04; 95% CI, 0.98-1.10). Merely, the gender interaction was shown to be statistically significant based on subgroup analyses and interaction tests. CONCLUSIONS A favorable association between DII and chronic diarrhea exists in adults in the United States. Nevertheless, additional long-term prospective studies are required to confirm and solidify those findings.
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Affiliation(s)
- Qing Zhao
- Department of Clinic Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Yue Xu
- Department of Clinic Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiangrui Li
- Department of Clinic Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Xiaotian Chen
- Department of Clinic Nutrition, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
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25
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Ding YY, Lan J, Wang Y, Pan Y, Song T, Liu S, Gu Z, Ge Y. Structure characterization of Grifola frondosa polysaccharide and its effect on insulin resistance in HFD-fed mice. NPJ Sci Food 2025; 9:3. [PMID: 39774946 PMCID: PMC11707143 DOI: 10.1038/s41538-024-00359-7] [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: 09/25/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025] Open
Abstract
Polysaccharide extracted from Grifola frondosa (GFP) was selected in this study. After preliminary separation, four factions were collected, named GFP-F1, GFP-F2, GFP-F3 and GFP-F4. GPF-F2 was further separated into two fractions, namely GFP-N1 and GFP-N2. The molecular weight of GFP-N1 and GFP-N2 was 3.323×103 kDa and 10.8 kDa, respectively. GFP-N1 was composed of glucose and galactose and 1 → 3, 1 → 4, and 1 → 6 glycosidic bonds. GFP-N2 was composed of glucose, galactose and mannose and 1 → 2, 1 → 3, 1 → 4, and 1 → 6 glycosidic bonds. GFP could significantly relieve the insulin resistance induced by HFD. GFP significantly alleviated gut microbiota disturbance caused by HFD and increased the production of short-chain fatty acids, and further reduced the expression of LPS/TLR4 inflammatory pathway. GFP significantly reduced the oxidative stress induced by HFD, increased the expression of the Nrf2/ARE signaling pathway. These results indicated that GFP could be developed as a potential ingredient for the management of insulin resistance.
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Affiliation(s)
- Yin-Yi Ding
- National Experimental Teaching Demonstration Center of Food Engineering and Quality and Safety, Food (Edible Fungi) Processing Technology Research Center, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China
| | - Jinchi Lan
- National Experimental Teaching Demonstration Center of Food Engineering and Quality and Safety, Food (Edible Fungi) Processing Technology Research Center, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China
| | - Yuxin Wang
- National Experimental Teaching Demonstration Center of Food Engineering and Quality and Safety, Food (Edible Fungi) Processing Technology Research Center, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China
| | - Yuxiang Pan
- National Experimental Teaching Demonstration Center of Food Engineering and Quality and Safety, Food (Edible Fungi) Processing Technology Research Center, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China
| | - Tianyuan Song
- National Experimental Teaching Demonstration Center of Food Engineering and Quality and Safety, Food (Edible Fungi) Processing Technology Research Center, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China
| | - Shizhu Liu
- Zhejiang Fangge Pharmaceutical Co. Ltd, Lishui, 323800, China
| | - Zhenyu Gu
- National Experimental Teaching Demonstration Center of Food Engineering and Quality and Safety, Food (Edible Fungi) Processing Technology Research Center, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China.
| | - Yujun Ge
- Central blood station of Jiaxing, Jiaxing, 314000, China
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26
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Nie T, You L, Tang F, Duan Y, Nepovimova E, Kuca K, Wu Q, Wei W. Microbiota-Gut-Brain Axis in Age-Related Neurodegenerative Diseases. Curr Neuropharmacol 2025; 23:524-546. [PMID: 39501955 DOI: 10.2174/1570159x23666241101093436] [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: 03/12/2024] [Revised: 05/23/2024] [Accepted: 05/30/2024] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.
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Affiliation(s)
- Tong Nie
- College of Life Science, Yangtze University, Jingzhou, 434025, China
| | - Li You
- College of Physical Education and Health, Chongqing College of International Business and Economics, Chongqing, 401520, China
| | - Fang Tang
- College of Humanities and New Media, Yangtze University, Jingzhou, 434025, China
| | - Yanhui Duan
- School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Králové, 500 03, Hradec Králové, Czech Republic
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Králové, 500 03, Hradec Králové, Czech Republic
- Biomedical Research Center, University Hospital of Hradec Králové, 500 05, Hradec Králové, Czech Republic
| | - Qinghua Wu
- College of Life Science, Yangtze University, Jingzhou, 434025, China
- Department of Chemistry, Faculty of Science, University of Hradec Králové, 500 03, Hradec Králové, Czech Republic
| | - Wei Wei
- State Key Laboratory for Managing Biotic and Chemical Threats to The Quality and Safety of Agro-Products, Key Laboratory of Traceability for Agricultural Genetically Modified Organisms, Ministry of Agriculture and Rural Affairs, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, China
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Albaladejo-Riad N, El Qendouci M, Cuesta A, Esteban MÁ. Ability of short-chain fatty acids to reduce inflammation and attract leucocytes to the inflamed skin of gilthead seabream (Sparus aurata L.). Sci Rep 2024; 14:31404. [PMID: 39732927 PMCID: PMC11682419 DOI: 10.1038/s41598-024-83033-y] [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: 03/19/2024] [Accepted: 12/11/2024] [Indexed: 12/30/2024] Open
Abstract
The aim of the study was to investigate the potential preventive use of short-chain fatty acids (SCFAs) to modulate inflammatory responses in gilthead seabream (Sparus aurata) skin. Initially, in vitro experiments were conducted to evaluate the effects of various concentrations of butyric acid, acetic acid and propionic acid, as well as their combination, on the cytotoxicity and cell viability of three different cell lines. The results determined the safe concentration of SCFAs, which was then used for an in vivo study. Fish were allocated into six groups and administered different combinations of SCFAs via intramuscular injection, followed by an injection of carrageenan as an inflammatory agent. Skin samples were taken from the injection site three hours post-administration and used to analyse gene expression and immunohistochemistry. The results demonstrated that treatment with SCFAs resulted in increased expression of proinflammatory and anti-inflammatory genes and leucocyte markers in the inflamed skin of fish. The highest gene expression and recruitment of acidophilic granulocytes were observed in fish injected with propionic acid and carrageenan. It is concluded that acetic acid is the most effective anti-inflammatory SCFA tested in gilthead seabream exposed to acute inflammation induced by carrageenan injection. Acetic acid exhibited the most pronounced direct anti-inflammatory effect, although propionic acid appeared to play a significant role in several mechanisms contributing to the resolution of inflammation and recruitment of immune cells to the site of carrageenan-inflamed area in gilthead seabream skin.
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Affiliation(s)
- Nora Albaladejo-Riad
- Immunobiology for Aquaculture Group, Department of Cell Biology and Histology, Faculty of Biology, Campus of International Excellence, Campus Mare Nostrum, University of Murcia, Murcia, Spain
| | - Mouna El Qendouci
- Laboratory of Biodiversity, Ecology and Genome, Department of Biology, Faculty of Sciences, University of Mohammed V, Rabat, Morocco
| | - Alberto Cuesta
- Immunobiology for Aquaculture Group, Department of Cell Biology and Histology, Faculty of Biology, Campus of International Excellence, Campus Mare Nostrum, University of Murcia, Murcia, Spain
| | - M Ángeles Esteban
- Immunobiology for Aquaculture Group, Department of Cell Biology and Histology, Faculty of Biology, Campus of International Excellence, Campus Mare Nostrum, University of Murcia, Murcia, Spain.
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Nakashima M, Suga N, Fukumoto A, Yoshikawa S, Matsuda S. Comprehension of gut microbiota and microRNAs may contribute to the development of innovative treatment tactics against metabolic disorders and psychiatric disorders. INTERNATIONAL JOURNAL OF PHYSIOLOGY, PATHOPHYSIOLOGY AND PHARMACOLOGY 2024; 16:111-125. [PMID: 39850247 PMCID: PMC11751546 DOI: 10.62347/wazh2090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 11/25/2024] [Indexed: 01/25/2025]
Abstract
Metabolic syndrome is a group of pathological disorders increasing the risk of serious diseases including cardiovascular disease, stroke, type 2 diabetes. Global widespread of the metabolic syndrome has put a heavy social burden. Interestingly, a crucial link between the metabolic syndrome and a psychiatric disorder may frequently coexist, in which certain shared mechanisms might play a role for the pathogenesis. In fact, some microRNAs (miRNAs) have been detected in the overlap pathology, suggesting a common molecular mechanism for the development of both disorders. Subsequent studies have revealed that these miRNAs and several metabolites of gut microbiota such as short chain fatty acids (SCFAs) might be involved in the development of both disorders, in which the association between gut and brain might play key roles with engram memory for the modulation of immune cells. Additionally, the correlation between brain and immunity might also influence the development of several diseases/disorders including metabolic syndrome. Brain could possess several inflammatory responses as an information of pathological images termed engrams. In other words, preservation of the engram memory might be achieved by a meta-plasticity mechanism that shapes the alteration of neuron linkages for the development of immune-related diseases. Therefore, it might be rational that metabolic syndrome and psychiatric disorders may belong to a group of immune-related diseases. Disrupting in gut microbiota may threaten the body homeostasis, leading to initiate a cascade of health problems. This concept may contribute to the development of superior therapeutic application with the usage of some functional components in food against metabolic and psychiatric disorders. This paper reviews advances in understanding the regulatory mechanisms of miRNAs with the impact to gut, liver and brain, deliberating the probable therapeutic techniques against these disorders.
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Affiliation(s)
- Moeka Nakashima
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Naoko Suga
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Akari Fukumoto
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Sayuri Yoshikawa
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Satoru Matsuda
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
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Al-Abbas NS, Shaer NA. Gut microbiome synthesizes important core metabolites to prevent cognitive decline and mitigate onset and progression of Alzheimer's disease. J Alzheimers Dis Rep 2024; 8:1705-1721. [PMID: 40034366 PMCID: PMC11863740 DOI: 10.1177/25424823241309024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 11/24/2024] [Indexed: 03/05/2025] Open
Abstract
Background This study explores how gut metabolites, produced through bacterial metabolism in the gut, influence neurological conditions like Alzheimer's disease (AD). Key metabolites such as succinate and short-chain fatty acids signal through the autonomic nervous system and can cross the blood-brain barrier, impacting central nervous system functions. Objective The aim is to examine the role of the gut microbiota in compensating for metabolic deficiencies in AD. By analyzing wild-type (WT) and APP/PS1 mice, the study investigates how the microbiome affects key metabolic processes and whether it can slow AD progression. Methods High-throughput sequencing data from the gut microbiomes of APP/PS1 transgenic AD model mice and age-matched WT C57BL/6 male mice were analyzed for microbial and metabolite profiles. Results Alpha and beta diversity analyses showed differences in microbial composition between groups. Partial least squares discriminant analysis and Anosim confirmed distinct microbiome profiles in WT and APP/PS1 mice. At the genus level, Vescimonas was more abundant in WT mice, while Odoribacter, Lacrimispora, Helicobacter, Bacteroides, and Alloprevotella were more prevalent in APP/PS1 mice. Conclusions While taxonomic differences did not directly link specific microorganisms to AD, functional analysis identified key metabolites-acetyl-CoA, glucose, succinate, lipids, choline, and acetylcholine-that may alleviate energy deficits and synaptic dysfunction. This study suggests that the microbiome may help compensate for AD-related impairments, opening avenues for microbiome-based therapies.
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Affiliation(s)
- Nouf S Al-Abbas
- Department of Biology, Jamoum University College, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Nehad A Shaer
- Department of Chemistry, Al Lieth University College, Umm Al-Qura University, Makkah, Saudi Arabia
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Cotoia A, Charitos IA, Corriero A, Tamburrano S, Cinnella G. The Role of Macronutrients and Gut Microbiota in Neuroinflammation Post-Traumatic Brain Injury: A Narrative Review. Nutrients 2024; 16:4359. [PMID: 39770985 PMCID: PMC11677121 DOI: 10.3390/nu16244359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/07/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
Traumatic brain injury (TBI) represents a multifaceted pathological condition resulting from external forces that disrupt neuronal integrity and function. This narrative review explores the intricate relationship between dietary macronutrients, gut microbiota (GM), and neuroinflammation in the TBI. We delineate the dual aspects of TBI: the immediate mechanical damage (primary injury) and the subsequent biological processes (secondary injury) that exacerbate neuronal damage. Dysregulation of the gut-brain axis emerges as a critical factor in the neuroinflammatory response, emphasizing the role of the GM in mediating immune responses. Recent evidence indicates that specific macronutrients, including lipids, proteins, and probiotics, can influence microbiota composition and in turn modulate neuroinflammation. Moreover, specialized dietary interventions may promote resilience against secondary insults and support neurological recovery post-TBI. This review aims to synthesize the current preclinical and clinical evidence on the potential of dietary strategies in mitigating neuroinflammatory pathways, suggesting that targeted nutrition and gut health optimization could serve as promising therapeutic modalities in TBI management.
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Affiliation(s)
- Antonella Cotoia
- Department of Intensive Care, University Hospital of Foggia, 71121 Foggia, Italy; (S.T.); (G.C.)
| | - Ioannis Alexandros Charitos
- Istituti Clinici Scientifici Maugeri IRCCS, Pneumology and Respiratory Rehabilitation Unit, “Istitute” of Bari, 70124 Bari, Italy;
- Doctoral School on Applied Neurosciences, Dipartimento di Biomedicina Traslazionale e Neuroscienze (DiBraiN), University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Alberto Corriero
- Department of Interdisciplinary Medicine-ICU Section, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Stefania Tamburrano
- Department of Intensive Care, University Hospital of Foggia, 71121 Foggia, Italy; (S.T.); (G.C.)
| | - Gilda Cinnella
- Department of Intensive Care, University Hospital of Foggia, 71121 Foggia, Italy; (S.T.); (G.C.)
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31
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Zeng M, Peng M, Liang J, Sun H. The Role of Gut Microbiota in Blood-Brain Barrier Disruption after Stroke. Mol Neurobiol 2024; 61:9735-9755. [PMID: 37498481 DOI: 10.1007/s12035-023-03512-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/13/2023] [Indexed: 07/28/2023]
Abstract
Growing evidence has proved that alterations in the gut microbiota have been linked to neurological disorders including stroke. Structural and functional disruption of the blood-brain barrier (BBB) is observed after stroke. In this context, there is pioneering evidence supporting that gut microbiota may be involved in the pathogenesis of stroke by regulating the BBB function. However, only a few experimental studies have been performed on stroke models to observe the BBB by altering the structure of gut microbiota, which warrant further exploration. Therefore, in order to provide a novel mechanism for stroke and highlight new insights into BBB modification as a stroke intervention, this review summarizes existing evidence of the relationship between gut microbiota and BBB integrity and discusses the mechanisms of gut microbiota on BBB dysfunction and its role in stroke.
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Affiliation(s)
- Meiqin Zeng
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China On Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory On Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Meichang Peng
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China On Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory On Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Jianhao Liang
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China On Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory On Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Haitao Sun
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China.
- Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China On Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory On Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
- Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Centre for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China.
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Liu Y, Zhang Y, Zhang J, Ren S, Cao Q, Kong H, Xu Q, Liu R. High-fat diet stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in collagen-induced arthritis rats. Nutr Metab (Lond) 2024; 21:95. [PMID: 39563394 DOI: 10.1186/s12986-024-00869-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 11/06/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, Dysbiosis of intestinal microbiota and their metabolites has been linked to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear.In this study, we explored the impact of high fat diet(HFD) on collagen-induced arthritis (CIA) rats and revealed its mechanisms based on gut microbiota and metabolomics. METHODS Based on diet and modeling, rats were divided into normal group (Con), CIA model group, HFD group (HFD), and HFD + CIA group (HCIA). The effect of HFD on arthritis in CIA rats were investigated based on the arthritis index (AI), weight, blood lipid levels, and inflammatory cytokines. Moreover, HE staining and micro-CT were performed to evaluated the effect of HFD on the pathology of joints and synovial tissues in CIA rats.16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS) were employed to explore changes in gut microbiota and short-chain fatty acids (SCFAs). RESULTS The AI scores, inflammatory cytokines and bone destruction parameters in the HCIA group were significantly higher than those in the other three groups. The results of 16S rRNA amplicon sequencing and metabolomics showed that compared with the other three groups, the expression of g_Muribaculaceae and butyric acid were reduced in the HCIA group. Spearman and linear correlation analyses revealed a positive correlation between g_Muribaculaceae abundance and butyric acid levels. CONCLUSIONS HFD stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in CIA rats.
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Affiliation(s)
- Yantong Liu
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Yang Zhang
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Jie Zhang
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Shuang Ren
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Qi Cao
- School of Acupuncture-Moxibustion and Tuina, Liaoning University of Traditional Chinese Medicine, Shenyang, 110001, China
| | - Hongxi Kong
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Qiangqiang Xu
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Ruoshi Liu
- Department of Traditional Chinese Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
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Ge Y, Cao Y, Zhang J, Li F, Wang J, Sun M, Liu Y, Long X, Guo W, Liu J, Fu S. GOS enhances BDNF-mediated mammary gland development in pubertal mice via the gut-brain axis. NPJ Biofilms Microbiomes 2024; 10:130. [PMID: 39562762 DOI: 10.1038/s41522-024-00607-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 11/11/2024] [Indexed: 11/21/2024] Open
Abstract
The "gut-brain axis" is involved in many physiological processes. However, its role in regulating mammary gland (MG) development remains unknown. In this study, we established the mice model of bilateral subdiaphragmatic vagotomy (Vago) to clarify the effects of "gut-brain axis" on MG development in pubertal mice. The results showed that Vago reduced the ratio of Lactobacillus and Bifidobacterium, neuronal excitability in the nucleus of solitary tract (NTS), and synthesis and secretion of BDNF, thereby slowing MG development. Transplanting the gut microbiota of Vago mice to recipient mice replicated these effects, and transplanting the gut microbiota of Control mice to Vago mice did not alleviate these effects. Galacto-Oligosaccharide (GOS), which up-regulates the ratio of Lactobacillus and Bifidobacterium, supplementation elevated NTS neuron excitability, synthesis and secretion of BDNF, and MG development, but Vago reversed these benefits. In conclusion, GOS enhances BDNF-mediated mammary gland development in pubertal mice via the "gut-brain axis".
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Grants
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
- 32202766 National Science Fund for Distinguished Young Scholars,China
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Affiliation(s)
- Yusong Ge
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Yu Cao
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Jialin Zhang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Feng Li
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Jiaxin Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Mingyang Sun
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Yuhao Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Xiaoyu Long
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Wenjin Guo
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Juxiong Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
| | - Shoupeng Fu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
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Hou L, Zhao J, Yin L, Dai L, Deng H, Jiang L. Brain injury in premature infants may be related to abnormal colonization of early gut microbiome. BMC Microbiol 2024; 24:483. [PMID: 39558267 PMCID: PMC11575211 DOI: 10.1186/s12866-024-03643-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 11/07/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother's body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16 S rRNA technology. METHODS Fecal samples from typical premature infants (non-brain injury group, n = 17) and those with brain injuries (brain injury group, n = 21) were collected on days 1, 3, and 7 after birth for 16 S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms' characteristics and differentiate the microorganisms between the two groups. RESULTS At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group. CONCLUSION Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota.
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Affiliation(s)
- Li Hou
- Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, No.1, Mao Yuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Jing Zhao
- Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, No.1, Mao Yuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China.
| | - Linlin Yin
- Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, No.1, Mao Yuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Lu Dai
- Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, No.1, Mao Yuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Hong Deng
- Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, No.1, Mao Yuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
| | - Lin Jiang
- Department of Neonatology, Affiliated Hospital of North Sichuan Medical College, No.1, Mao Yuan South Road, Shunqing District, Nanchong, 637000, Sichuan, China
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Gold A, Kaye S, Gao J, Zhu J. Propionate Decreases Microglial Activation but Impairs Phagocytic Capacity in Response to Aggregated Fibrillar Amyloid Beta Protein. ACS Chem Neurosci 2024; 15:4010-4020. [PMID: 39394077 DOI: 10.1021/acschemneuro.4c00370] [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: 10/13/2024] Open
Abstract
Microglia, the innate immune cell of the brain, are a principal player in Alzheimer's disease (AD) pathogenesis. Their surveillance of the brain leads to interaction with the protein aggregates that drive AD pathogenesis, most notably Amyloid Beta (Aβ). Microglia attempt to clear and degrade Aβ using phagocytic machinery, spurring damaging neuroinflammation in the process. Thus, modulation of the microglial response to Aβ is crucial in mitigating AD pathophysiology. SCFAs, microbial byproducts of dietary fiber fermentation, are blood-brain barrier permeable molecules that have recently been shown to modulate microglial function. It is unclear whether propionate, one representative SCFA, has beneficial or detrimental effects on microglia in AD. Thus, we investigated its impact on microglial Aβ response in vitro. Using a multiomics approach, we characterized the transcriptomic, metabolomic, and lipidomic responses of immortalized murine microglia following 1 h of Aβ stimulation, as well as characterizing Aβ phagocytosis and secretion of reactive nitrogen species. Propionate blunted the early inflammatory response driven by Aβ, downregulating the expression of many Aβ-stimulated immune genes, including those regulating inflammation, the immune complement system, and chemotaxis. Further, it reduced the expression of Apoe and inflammation-promoting Aβ-binding scavenger receptors such as Cd36 and Msr1 in favor of inflammation-dampening Lpl, although this led to impaired phagocytosis. Finally, propionate shifted microglial metabolism, altering phospholipid composition and diverting arginine metabolism, resulting in decreased nitric oxide production. Altogether, our data demonstrate a modulatory role of propionate on microglia that may dampen immune activation in response to Aβ, although at the expense of phagocytic capacity.
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Affiliation(s)
- Andrew Gold
- Human Nutrition Program and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
| | - Sarah Kaye
- Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, United States
| | - Jie Gao
- Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, United States
| | - Jiangjiang Zhu
- Human Nutrition Program and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
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Bano N, Khan S, Ahamad S, Kanshana JS, Dar NJ, Khan S, Nazir A, Bhat SA. Microglia and gut microbiota: A double-edged sword in Alzheimer's disease. Ageing Res Rev 2024; 101:102515. [PMID: 39321881 DOI: 10.1016/j.arr.2024.102515] [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: 04/23/2024] [Revised: 09/06/2024] [Accepted: 09/19/2024] [Indexed: 09/27/2024]
Abstract
The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.
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Affiliation(s)
- Nargis Bano
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Sameera Khan
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Shakir Ahamad
- Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
| | - Jitendra Singh Kanshana
- Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburg, PA, USA.
| | - Nawab John Dar
- CNB, SALK Institute of Biological Sciences, La Jolla, CA 92037, USA.
| | - Sumbul Khan
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India
| | - Aamir Nazir
- Division of Neuroscience and Ageing Biology, CSIR-Central Drug Research Institute, Lucknow, UP, India; Academy of Scientific and Innovative Research, New Delhi, India.
| | - Shahnawaz Ali Bhat
- Department of Zoology, Aligarh Muslim University, Aligarh 202002, India.
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Singh I, Anand S, Gowda DJ, Kamath A, Singh AK. Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders. Biogerontology 2024; 25:899-922. [PMID: 39177917 PMCID: PMC11486790 DOI: 10.1007/s10522-024-10128-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 08/05/2024] [Indexed: 08/24/2024]
Abstract
The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.
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Affiliation(s)
- Ishika Singh
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Shashi Anand
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Deepashree J Gowda
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Amitha Kamath
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India
| | - Abhishek Kumar Singh
- Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India.
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Wiens KR, Brooks NAH, Riar I, Greuel BK, Lindhout IA, Klegeris A. Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT 2 Receptor-Dependent Manner. Molecules 2024; 29:5084. [PMID: 39519725 PMCID: PMC11547910 DOI: 10.3390/molecules29215084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/16/2024] [Accepted: 10/17/2024] [Indexed: 11/16/2024] Open
Abstract
Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood-brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT2ARs) on neurons. Since microglia express all three 5-HT2R isoforms, we hypothesized that, by interacting with these receptors, psilocin beneficially modulates select neuroimmune functions of microglia. We used microglia-like cell lines to demonstrate that psilocin, at non-toxic concentrations, did not affect the secretion of tumor necrosis factor (TNF) by immune-stimulated microglial cells, but significantly inhibited their phagocytic activity, the release of reactive oxygen species (ROS), and nitric oxide (NO) production. The inhibitory activity of psilocin on the latter two functions was similar to that of two selective 5-HT2R agonists, namely, 25I-NBOH and Ro60-0175. The role of this subfamily of receptors was further demonstrated by the application of 5-HT2R antagonists cyproheptadine and risperidone. Psilocin should be considered a novel drug candidate that might be effective in treating neuroimmune disorders, such as neurodegenerative diseases, where reactive microglia are significant contributors.
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Affiliation(s)
| | | | | | | | | | - Andis Klegeris
- Laboratory of Cellular and Molecular Pharmacology, Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC V1V 1V7, Canada
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Park KJ, Gao Y. Gut-brain axis and neurodegeneration: mechanisms and therapeutic potentials. Front Neurosci 2024; 18:1481390. [PMID: 39513042 PMCID: PMC11541110 DOI: 10.3389/fnins.2024.1481390] [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: 08/15/2024] [Accepted: 10/07/2024] [Indexed: 11/15/2024] Open
Abstract
This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors.
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Affiliation(s)
| | - Yao Gao
- Vascular Biology Program, Boston Children’s Hospital, Boston, MA, United States
- Department of Surgery, Harvard Medical School, Boston, MA, United States
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40
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Lin J, Chen D, Yan Y, Pi J, Xu J, Chen L, Zheng B. Gut microbiota: a crucial player in the combat against tuberculosis. Front Immunol 2024; 15:1442095. [PMID: 39502685 PMCID: PMC11534664 DOI: 10.3389/fimmu.2024.1442095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 09/30/2024] [Indexed: 11/08/2024] Open
Abstract
The mammalian gastrointestinal tract quickly becomes densely populated with foreign microorganisms shortly after birth, thereby establishing a lifelong presence of a microbial community. These commensal gut microbiota serve various functions, such as providing nutrients, processing ingested compounds, maintaining gut homeostasis, and shaping the intestinal structure in the host. Dysbiosis, which is characterized by an imbalance in the microbial community, is closely linked to numerous human ailments and has recently emerged as a key factor in health prognosis. Tuberculosis (TB), a highly contagious and potentially fatal disease, presents a pressing need for improved methods of prevention, diagnosis, and treatment strategies. Thus, we aim to explore the latest developments on how the host's immune defenses, inflammatory responses, metabolic pathways, and nutritional status collectively impact the host's susceptibility to or resilience against Mycobacterium tuberculosis infection. The review addresses how the fluctuations in the gut microbiota not only affect the equilibrium of these physiological processes but also indirectly influence the host's capacity to resist M. tuberculosis. This work highlights the central role of the gut microbiota in the host-microbe interactions and provides novel insights for the advancement of preventative and therapeutic approaches against tuberculosis.
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Affiliation(s)
- Jie Lin
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China
- Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, China
| | - Dongli Chen
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China
- Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, China
| | - Yongen Yan
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China
- Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, China
| | - Jiang Pi
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China
- Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, China
- The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Junfa Xu
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China
- Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, China
| | - Lingming Chen
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China
- Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, China
- The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Biying Zheng
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan, Guangdong, China
- Institute of Laboratory Medicine, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, China
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41
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Zhao J, Lei Y, Zhang X, Li Z. A bibliometric analysis of global research on short chain fatty acids in neurological diseases. Medicine (Baltimore) 2024; 103:e40102. [PMID: 39465784 PMCID: PMC11479477 DOI: 10.1097/md.0000000000040102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 09/26/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUND The interest on short chain fatty acids (SCFAs) regulating the progress of neurological diseases has gained significant attention in recent years. This bibliometric analysis aimed to provide insights into the current state and future trends of global research on SCFAs in neurological research. METHODS To analysis the general trend of publications, the scientific output in this field from 1995 to 2024 was first retrieved from the Web of Science Core Collection, Scopus, and PubMed with SCFAs-related and neurological diseases related terms as the subjects. Based on above publication analysis, rapid development stage was marked as 2016 to 2024 and 878 relevant original articles in rapid development stage was retrieved with the time limit from 2016 to 2024. Key bibliometric indicators were calculated and evaluated using CiteSpace with these 878 articles. RESULTS SCFAs are related to the occurrence and development of neurological diseases. China and the USA have contributed in a significant way to foster a better understanding on SCFAs in neurological diseases. The hot theme of research have gradually shifted from neurodegenerative diseases to psychical diseases. In the aspect of mechanism research, the current hotspot is inflammation. SCFAs are able to modulate oxidative stress and microglia maturation, morphology and function to intervene in the development of neurological diseases and thus SCFAs interventions are promising to treat neurological diseases. 2016 to 2024 is the fast-developing stage in this field. In this stage the publications dramatically increased and were of high quality. CONCLUSION SCFAs in neurological research will continue to be an active area in the near future. Future trends might be correlation analysis and neurotherapeutics of SCFAs on patients with psychical diseases and deeper mechanism research is still needed.
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Affiliation(s)
- Jiuhong Zhao
- Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China
- Department of Human Anatomy and Histology, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Yihan Lei
- Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Xinyuan Zhang
- Department of Forensic Clinical Medicine, School of Forensic Medicine, China Medical University, Shenyang, China
| | - Zhihong Li
- Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China
- Department of Human Anatomy and Histology, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China
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Jang D, Shin J, Shim E, Ohtani N, Jeon OH. The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review. Aging Cell 2024; 23:e14315. [PMID: 39148278 PMCID: PMC11464129 DOI: 10.1111/acel.14315] [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: 03/26/2024] [Revised: 07/24/2024] [Accepted: 08/06/2024] [Indexed: 08/17/2024] Open
Abstract
The intricate interplay between cellular senescence and alterations in the gut microbiome emerges as a pivotal axis in the aging process, increasingly recognized for its contribution to systemic inflammation, physiological decline, and predisposition to age-associated diseases. Cellular senescence, characterized by a cessation of cell division in response to various stressors, induces morphological and functional changes within tissues. The complexity and heterogeneity of senescent cells, alongside the secretion of senescence-associated secretory phenotype, exacerbate the aging process through pro-inflammatory pathways and influence the microenvironment and immune system. Concurrently, aging-associated changes in gut microbiome diversity and composition contribute to dysbiosis, further exacerbating systemic inflammation and undermining the integrity of various bodily functions. This review encapsulates the burgeoning research on the reciprocal relationship between cellular senescence and gut dysbiosis, highlighting their collective impact on age-related musculoskeletal diseases, including osteoporosis, sarcopenia, and osteoarthritis. It also explores the potential of modulating the gut microbiome and targeting cellular senescence as innovative strategies for healthy aging and mitigating the progression of aging-related conditions. By exploring targeted interventions, including the development of senotherapeutic drugs and probiotic therapies, this review aims to shed light on novel therapeutic avenues. These strategies leverage the connection between cellular senescence and gut microbiome alterations to advance aging research and development of interventions aimed at extending health span and improving the quality of life in the older population.
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Affiliation(s)
- Dong‐Hyun Jang
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
| | - Ji‐Won Shin
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
| | - Eunha Shim
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
| | - Naoko Ohtani
- Department of PathophysiologyOsaka Metropolitan University Graduate School of MedicineOsakaJapan
| | - Ok Hee Jeon
- Department of Biomedical SciencesKorea University College of MedicineSeoulRepublic of Korea
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Hong B. Gut flora reflects potential risk factors for cognitive dysfunction in patients with epilepsy. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2024; 43:155. [PMID: 39342383 PMCID: PMC11439293 DOI: 10.1186/s41043-024-00639-8] [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: 05/09/2024] [Accepted: 09/04/2024] [Indexed: 10/01/2024]
Abstract
OBJECTIVE This cross-sectional study aims to analyze the differences in gut flora between patients with epilepsy with and without cognitive impairment and normal subjects. METHODS One hundred patients with epilepsy who came to our hospital from 2020.12 to 2022.12 (epilepsy group) were selected, and another 100 family members of the patients were selected as the control group (control group). Patients with epilepsy were further classified by the MMSE scale into 62 patients with combined cognitive impairment (Yes group) and 38 patients without cognitive impairment (No group). Detection of gut flora in feces by 16 S rRNA high-throughput sequencing. Logistic regression was used to analyze risk factors for cognitive dysfunction in patients with epilepsy. RESULTS There were more significant differences in the structure and composition of the gut flora between patients in the epilepsy group and the control group, but no significant differences in diversity analysis (P > 0.05). Actinobacteriota, Faecalibacterium and Collinsella were significantly lower in the Yes group than in the No group (P < 0.05), and the Alpha diversity index was numerically slightly smaller than in the No group, with the PCoA analysis demonstrating a more dispersed situation in both groups. Five metabolic pathways, including glycolysis and heterolactic fermentation, were upregulated in the Yes group. LEfSe analysis showed that five groups of bacteria, including Coriobacteriaceae and Collinsella, were selected as marker species for the presence or absence of comorbid cognitive impairment. Of these, Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy combined with cognitive impairment. CONCLUSION There was an imbalance in the gut flora of patients with epilepsy compared to healthy controls. The gut flora of patients with epilepsy with cognitive dysfunction differs significantly from that of patients without cognitive dysfunction. Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy with cognitive dysfunction and can be used as an indicator for the observation of epilepsy with cognitive dysfunction.
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Affiliation(s)
- BingCong Hong
- Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, China.
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Gao Y, Yao Q, Meng L, Wang J, Zheng N. Double-side role of short chain fatty acids on host health via the gut-organ axes. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2024; 18:322-339. [PMID: 39290857 PMCID: PMC11406094 DOI: 10.1016/j.aninu.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 01/29/2024] [Accepted: 05/14/2024] [Indexed: 09/19/2024]
Abstract
Short chain fatty acids (SCFA) exist in dietary foods and are produced by the fermentation of gut microbiota, and are considered an important element for regulating host health. Through blood circulation, SCFA produced in the gut and obtained from foods have an impact on the intestinal health as well as vital organs of the host. It has been recognized that the gut is the "vital organ" in the host. As the gut microbial metabolites, SCFA could create an "axis" connecting the gut and to other organs. Therefore, the "gut-organ axes" have become a focus of research in recent years to analyze organism health. In this review, we summarized the sources, absorption properties, and the function of SCFA in both gut and other peripheral tissues (brain, kidney, liver, lung, bone and cardiovascular) in the way of "gut-organ axes". Short chain fatty acids exert both beneficial and pathological role in gut and other organs in various ways, in which the beneficial effects are more pronounced. In addition, the beneficial effects are reflected in both preventive and therapeutic effects. More importantly, the mechanisms behinds the gut and other tissues provided insight into the function of SCFA, assisting in the development of novel preventive and therapeutic strategies for maintaining the host health.
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Affiliation(s)
- Yanan Gao
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Qianqian Yao
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Department of Food Science, Faculty of Veterinary Medicine, University of Liège, Liège 4000, Belgium
| | - Lu Meng
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Jiaqi Wang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Nan Zheng
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Milk and Milk Products Inspection Center of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
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Liu Y, Jia N, Tang C, Long H, Wang J. Microglia in Microbiota-Gut-Brain Axis: A Hub in Epilepsy. Mol Neurobiol 2024; 61:7109-7126. [PMID: 38366306 DOI: 10.1007/s12035-024-04022-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/06/2024] [Indexed: 02/18/2024]
Abstract
There is growing concern about the role of the microbiota-gut-brain axis in neurological illnesses, and it makes sense to consider microglia as a critical component of this axis in the context of epilepsy. Microglia, which reside in the central nervous system, are dynamic guardians that monitor brain homeostasis. Microglia receive information from the gut microbiota and function as hubs that may be involved in triggering epileptic seizures. Vagus nerve bridges the communication in the axis. Essential axis signaling molecules, such as gamma-aminobutyric acid, 5-hydroxytryptamin, and short-chain fatty acids, are currently under investigation for their participation in drug-resistant epilepsy (DRE). In this review, we explain how vagus nerve connects the gut microbiota to microglia in the brain and discuss the emerging concepts derived from this interaction. Understanding microbiota-gut-brain axis in epilepsy brings hope for DRE therapies. Future treatments can focus on the modulatory effect of the axis and target microglia in solving DRE.
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Affiliation(s)
- Yuyang Liu
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- The First Clinical Medicine College, Southern Medical University, Guangzhou, China
- Neural Networks Surgery Team, Southern Medical University, Guangzhou, China
| | - Ningkang Jia
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- Neural Networks Surgery Team, Southern Medical University, Guangzhou, China
- The Second Clinical Medicine College, Southern Medical University, Guangzhou, China
| | - Chuqi Tang
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- The First Clinical Medicine College, Southern Medical University, Guangzhou, China
- Neural Networks Surgery Team, Southern Medical University, Guangzhou, China
| | - Hao Long
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- The First Clinical Medicine College, Southern Medical University, Guangzhou, China
| | - Jun Wang
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
- The First Clinical Medicine College, Southern Medical University, Guangzhou, China.
- Neural Networks Surgery Team, Southern Medical University, Guangzhou, China.
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Li S, Zhao L, Xiao J, Guo Y, Fu R, Zhang Y, Xu S. The gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances. Mol Cell Biochem 2024; 479:2217-2243. [PMID: 37787835 DOI: 10.1007/s11010-023-04853-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/06/2023] [Indexed: 10/04/2023]
Abstract
There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.
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Affiliation(s)
- Songlin Li
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Linna Zhao
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin, China
| | - Jie Xiao
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuying Guo
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin, China
| | - Rong Fu
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yunsha Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shixin Xu
- Medical Experiment Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin, China.
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Zampieri G, Cabrol L, Urra C, Castro-Nallar E, Schwob G, Cleary D, Angione C, Deacon RMJ, Hurley MJ, Cogram P. Microbiome alterations are associated with apolipoprotein E mutation in Octodon degus and humans with Alzheimer's disease. iScience 2024; 27:110348. [PMID: 39148714 PMCID: PMC11324989 DOI: 10.1016/j.isci.2024.110348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 05/22/2024] [Accepted: 06/20/2024] [Indexed: 08/17/2024] Open
Abstract
Gut microbiome dysbiosis is linked to many neurological disorders including Alzheimer's disease (AD). A major risk factor for AD is polymorphism in the apolipoprotein E (APOE) gene, which affects gut microbiome composition. To explore the gut-brain axis in AD, long-lived animal models of naturally developing AD-like pathologies are needed. Octodon degus (degu) exhibit spontaneous AD-like symptoms and ApoE mutations, making them suitable for studying the interplay between AD genetic determinants and gut microbiome. We analyzed the association between APOE genotype and gut microbiome in 50 humans and 32 degu using16S rRNA gene amplicon sequencing. Significant associations were found between the degu ApoE mutation and gut microbial changes in degu, notably a depletion of Ruminococcaceae and Akkermansiaceae and an enrichment of Prevotellaceae, mirroring patterns seen in people with AD. The altered taxa were previously suggested to be involved in AD, validating the degu as an unconventional model for studying the AD/microbiome crosstalk.
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Affiliation(s)
- Guido Zampieri
- School of Computing, Engineering and Digital Technologies, Department of Computer Science and Information Systems, Teesside University, Middlesbrough, Tees Valley TS1 3BX, UK
| | - Léa Cabrol
- Institute of Ecology and Biodiversity, Department of Ecological Sciences, Faculty of Science, Universidad de Chile, Las Palmeras 3425, Santiago 7800003, Chile
- Aix Marseille University, University Toulon, CNRS, IRD, Méditerranéen Institute of Océanographie (MIO) UM 110, Avenue de Luminy, 13009 Marseille, France
- Millennium Institute Biodiversity of Antarctic and Subantarctic Ecosystems (BASE), Las Palmeras 3425, Santiago 7800003, Chile
| | - Claudio Urra
- Institute of Ecology and Biodiversity, Department of Ecological Sciences, Faculty of Science, Universidad de Chile, Las Palmeras 3425, Santiago 7800003, Chile
| | - Eduardo Castro-Nallar
- Center for Bioinformatics and Integrative Biology, Universidad Andres Bello, Avenida República 239, Santiago 7591538, Chile
| | - Guillaume Schwob
- Millennium Institute Biodiversity of Antarctic and Subantarctic Ecosystems (BASE), Las Palmeras 3425, Santiago 7800003, Chile
| | - David Cleary
- School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
| | - Claudio Angione
- School of Computing, Engineering and Digital Technologies, Department of Computer Science and Information Systems, Teesside University, Middlesbrough, Tees Valley TS1 3BX, UK
| | - Robert M J Deacon
- Institute of Ecology and Biodiversity, Department of Ecological Sciences, Faculty of Science, Universidad de Chile, Las Palmeras 3425, Santiago 7800003, Chile
| | - Michael J Hurley
- Institute of Ecology and Biodiversity, Department of Ecological Sciences, Faculty of Science, Universidad de Chile, Las Palmeras 3425, Santiago 7800003, Chile
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK
| | - Patricia Cogram
- Institute of Ecology and Biodiversity, Department of Ecological Sciences, Faculty of Science, Universidad de Chile, Las Palmeras 3425, Santiago 7800003, Chile
- Department of Anatomy and Neurobiology, School of Medicine, B240 Med Sci, University of California, Irvine, Irvine, CA 92697, USA
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Grijaldo-Alvarez SJB, Alvarez MRS, Schindler RL, Oloumi A, Hernandez N, Seales T, Angeles JGC, Nacario RC, Completo GC, Zivkovic AM, Bruce German J, Lebrilla CB. N-Glycan profile of the cell membrane as a probe for lipopolysaccharide-induced microglial neuroinflammation uncovers the effects of common fatty acid supplementation. Food Funct 2024; 15:8258-8273. [PMID: 39011570 PMCID: PMC11668514 DOI: 10.1039/d4fo01598c] [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: 07/17/2024]
Abstract
Altered N-glycosylation of proteins on the cell membrane is associated with several neurodegenerative diseases. Microglia are an ideal model for studying glycosylation and neuroinflammation, but whether aberrant N-glycosylation in microglia can be restored by diet remains unknown. Herein, we profiled the N-glycome, proteome, and glycoproteome of the human microglia following lipopolysaccharide (LPS) induction to probe the impact of dietary and gut microbe-derived fatty acids-oleic acid, lauric acid, palmitic acid, valeric acid, butyric acid, isobutyric acid, and propionic acid-on neuroinflammation using liquid chromatography-tandem mass spectrometry. LPS changed N-glycosylation in the microglial glycocalyx altering high mannose and sialofucosylated N-glycans, suggesting the dysregulation of mannosidases, fucosyltransferases, and sialyltransferases. The results were consistent as we observed the restoration effect of the fatty acids, especially oleic acid, on the LPS-treated microglia, specifically on the high mannose and sialofucosylated glycoforms of translocon-associated proteins, SSRA and SSRB along with the cell surface proteins, CD63 and CD166. In addition, proteomic analysis and in silico modeling substantiated the potential of fatty acids in reverting the effects of LPS on microglial N-glycosylation. Our results showed that N-glycosylation is likely affected by diet by restoring alterations following LPS challenge, which may then influence the disease state.
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Affiliation(s)
- Sheryl Joyce B Grijaldo-Alvarez
- Department of Chemistry, University of California, Davis, 95616, USA.
- Institute of Chemistry, University of the Philippines Los Baños, Philippines, 4031.
| | | | | | - Armin Oloumi
- Department of Chemistry, University of California, Davis, 95616, USA.
| | - Noah Hernandez
- Department of Chemistry, University of California, Davis, 95616, USA.
| | - Tristan Seales
- Department of Chemistry, University of California, Davis, 95616, USA.
| | - Jorge Gil C Angeles
- Philippine Genome Center - Program for Agriculture, Livestock, Fisheries and Forestry, University of the Philippines Los Baños, Philippines, 4031.
| | - Ruel C Nacario
- Institute of Chemistry, University of the Philippines Los Baños, Philippines, 4031.
| | - Gladys C Completo
- Institute of Chemistry, University of the Philippines Los Baños, Philippines, 4031.
| | - Angela M Zivkovic
- Department of Nutrition, University of California, Davis, 95616, USA.
| | - J Bruce German
- Department of Food Science and Technology, University of California, Davis, 95616, USA.
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Cherednichenko AS, Mozdor PV, Oleynikova TK, Khatam PA, Nastueva FM, Kovalenkov KO, Serdinova AS, Osmaeva AK, Rovchak AI, Esikova YY, Shogenova MK, Akhmedov KI, Amirgamzaev MR, Batyrshina ER. A relationship between intestinal microbiome and epilepsy: potential treatment options for drug-resistant epilepsy. EPILEPSY AND PAROXYSMAL CONDITIONS 2024; 16:250-265. [DOI: 10.17749/2077-8333/epi.par.con.2024.190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Background. According to the World Health Organization, about 50 million people worldwide suffer from epilepsy. Almost 1/3 of patients are diagnosed with drug-resistant epilepsy (DRE). A relationship between intestinal microbiome (IM) and the central nervous system carried out throughout life via bidirectional dynamic network exists. It has been evidenced that IM profile becomes altered in patients with DRE.Objective: to summarize the current literature data on the role for microbiome-gut-brain axis in DRE, as well as to assess an importance of IM composition changes as a prognostic marker for developing DRE.Material and methods. The authors conducted a search for publications in the electronic databases PubMed/MEDLINE and eLibrary, as well as Google Scholar search engine. The evaluation of the articles was carried out in accordance with the PRISMA recommendations. Based on the search, 4,158 publications were retrieved from PubMed/MEDLINE database, 173 – from eLibrary, and 1,100 publications found with Google Scholar. After the selection procedure, 121 studies were included in the review.Results. The review provides convincing evidence about a correlation between IM and DRE demonstrating overt differences in IM composition found in patients with epilepsy related to drug sensitivity. IM dysbiosis can be corrected by exogenous interventions such as ketogenic diet, probiotic treatment and fecal microbiota transplantation subsequently resulting in altered brain neurochemical signaling and, therefore, alleviating epileptic activity.Conclusion. A ketogenic diet, probiotics and antibiotics may have some potential to affect epilepsy by correcting IM dysbiosis, but the current studies provide no proper level of evidence. Future clinical multicenter trials should use standardized protocols and a larger-scale patient sample to provide more reliable evidence. Moreover, further fundamental investigations are required to elucidate potential mechanisms and therapeutic targets.
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50
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Madani AMA, Muhlisin M, Kurniawati A, Baskara AP, Anas MA. Dietary jack bean ( Canavalia ensiformis L.) supplementation enhanced intestinal health by modulating intestinal integrity and immune responses of broiler chickens. Heliyon 2024; 10:e34389. [PMID: 39130426 PMCID: PMC11315099 DOI: 10.1016/j.heliyon.2024.e34389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 07/04/2024] [Accepted: 07/09/2024] [Indexed: 08/13/2024] Open
Abstract
This study investigated the influence of supplementing with jack beans on jejunal morphology, cecal short-chain fatty acids production, gene expression both of pro- and anti-inflammatory cytokines and tight junctions. Four treatment groups including 288 Indian River chicks that were one day old were randomized at random. While the treatment groups received jack bean supplementation at levels of 5 %, 10 %, and 15 %, the control group (0 %) was given a basal diet. For 11-35 days, each treatment consisted of 8 pens with 9 birds each. Supplementing with jack beans significantly enhanced butyrate production (P < 0.001), while at 10 % supplementation did not differ from control. Villus height (VH) and the ratio (VH:CD) were significantly (P < 0.001) increased by dietary treatments, while villus width (VW) and crypt depth (CD) were significantly (P < 0.05) decreased. TLR-3, TNF-a, and IL-6 were all significantly (P < 0.001) increased by dietary supplementation. However, at 15 %, TLR-3 and IL-6 were same with control. IL-18 was significantly (P < 0.05) decreased at 15 %. IL-10 decreased significantly (P < 0.001), but at 10 % same with control. At 5 and 10 %, IL-13 increased significantly (P < 0.001), whereas dietary treatments decreased at 15 % compared to control. Although ZO1 decreased significantly (P < 0.001) and OLCN increased significantly (P < 0.001), both ZO1 and OCLN were not significantly different from the control at 15 %. Dietary treatments significantly (P < 0.001) increased CLDN1 but did not differ from the control at 10 %. JAM2 decreased significantly (P < 0.001) with dietary treatments. In conclusion, jack bean supplementation may increase broiler chicken performance and intestinal health due to butyrate production. It may affect intestinal morphology and integrity by upregulating a tight junction protein gene. Jack beans also impacted jejunum immune responses and inflammatory cytokine gene expression.
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Affiliation(s)
- Abd Majid Ahmad Madani
- Animal Nutrition and Feed Science Department, Faculty of Animal Science, Universitas Gadjah Mada, Indonesia
| | - Muhlisin Muhlisin
- Animal Nutrition and Feed Science Department, Faculty of Animal Science, Universitas Gadjah Mada, Indonesia
| | - Asih Kurniawati
- Animal Nutrition and Feed Science Department, Faculty of Animal Science, Universitas Gadjah Mada, Indonesia
| | - Aji Praba Baskara
- Animal Nutrition and Feed Science Department, Faculty of Animal Science, Universitas Gadjah Mada, Indonesia
| | - Muhsin Al Anas
- Animal Nutrition and Feed Science Department, Faculty of Animal Science, Universitas Gadjah Mada, Indonesia
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