Gut microorganisms act together to exacerbate inflammation in spinal cords

Miyauchi, Eiji; Kim, Seok Won; Suda, Wataru; Kawasumi, Masami; Onawa, Satoshi; Taguchi‐Atarashi, Naoko; Morita, Hidetoshi; Taylor, Todd D.; Hattori, Masahira; Ohno, Hiroshi

doi:10.1038/s41586-020-2634-9

Cited by 195 publications

(162 citation statements)

References 37 publications

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“…Miyauchi E. and colleagues showed that the in vivo treatment with ampicillin induced the complete depletion of Allobaculum bacteria from the small bowel. Monocolonization with this bacterium induced the generation of Th17 cells in the small intestinal lamina propria and systemically, and increased severity of EAE, compared to GF mice ( 152 ). However, the disease development was less severe than under conventional hygiene conditions.…”

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 97%

“…Briefly, commensal-reactive IgA-producing cells expressed IL-10, and the production of IL-10 (partially together with iNOS, but not IgA itself) was essential to ameliorate EAE ( 151 ). Lately, in the classical acute EAE model, ampicillin administration alone ameliorated the EAE development ( 152 ) with a reduction of proliferating CD4 + autoreactive T cells. Miyauchi E. and colleagues showed that the in vivo treatment with ampicillin induced the complete depletion of Allobaculum bacteria from the small bowel.…”

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

“…The authors focused then their attention on bacteria homing to the small intestine that could favor the generation and proliferation of autoreactive T cells via presentation of cross-reactive antigens. Mice bearing a T cell-receptor (TCR) specific for myelin-oligodendrocyte glycoprotein (MOG) (2D2 mice) showed higher number of CD4 + T cells in the small intestinal lamina propria compared to their wild-type counterpart ( 152 ). Some candidate mimicry peptides, like UvrABC system protein A (UvrA), were expressed by L. reuteri , and aminopeptidase by strains of Allobaculum ( 152 ).…”

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

“…Mice bearing a T cell-receptor (TCR) specific for myelin-oligodendrocyte glycoprotein (MOG) (2D2 mice) showed higher number of CD4 + T cells in the small intestinal lamina propria compared to their wild-type counterpart ( 152 ). Some candidate mimicry peptides, like UvrABC system protein A (UvrA), were expressed by L. reuteri , and aminopeptidase by strains of Allobaculum ( 152 ). Interestingly, L. reuteri monocolonization did not affect the severity of EAE.…”

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

“…Interestingly, L. reuteri monocolonization did not affect the severity of EAE. However, the bi-colonization with Allobaculum and L. reuteri together activated MOG-specific T cells toward a pathogenic Th17 phenotype and worsened EAE, with demyelination and cell infiltration in the spinal cord ( 152 ). This study highlighted the important synergistic potential of several intestinal bacteria, along the entire intestinal tract and perhaps residing even in close contact with the mucus layer, in mediating the disease development through molecular mimicry.…”

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

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The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

2020

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The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

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Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 97%

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

Section: Neurological Diseases: Microbial Effect On the Host Immune Amentioning

confidence: 99%

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The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

2020

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Gut microbiome is associated with multiple sclerosis activity in children

Horton

McCauley

Fadrosh

et al. 2021

Ann Clin Transl Neurol

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Objective To identify features of the gut microbiome associated with multiple sclerosis activity over time. Methods We used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric‐onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes and networks identified from weighted genetic correlation network analyses. Prentice‐Williams‐Peterson Cox proportional hazards models estimated the associations between features and three disease activity outcomes: clinical relapses and both new/enlarging T2 lesions and new gadolinium‐enhancing lesions on brain MRI. Analyses were adjusted for age, sex, and disease‐modifying therapies. Results Participants were followed, on average, 2.1 years. Five microbes were nominally associated with all three disease activity outcomes after multiple testing correction. These included butyrate producers Odoribacter (relapse hazard ratio = 0.46, 95% confidence interval: 0.24, 0.88) and Butyricicoccus (relapse hazard ratio = 0.49, 95% confidence interval: 0.28, 0.88). Two networks of co‐occurring gut microbes were significantly associated with a higher hazard of both MRI outcomes (gadolinium‐enhancing lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.29 (1.08, 1.54) and 1.42 (1.18, 1.71), respectively; T2 lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.34 (1.15, 1.56) and 1.41 (1.21, 1.64), respectively). Metagenomic predictions of these networks demonstrated enrichment for amino acid biosynthesis pathways. Interpretation Both individual and networks of gut microbes were associated with longitudinal multiple sclerosis activity. Known functions and metagenomic predictions of these microbes suggest the important role of butyrate and amino acid biosynthesis pathways. This provides strong support for future development of personalized microbiome interventions to modify multiple sclerosis disease activity.

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Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis

Wang,

Jia,

et al. 2023

Advanced Science

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Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate‐induced colitis in mice. Based on flow cytometry, colitis‐associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell‐null Rag1−/− mice or upon anti‐IL‐17‐A antibody‐treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA‐driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti‐colitis effect in RAR‐α ‐mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA‐SAA1/2‐Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

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Gut microorganisms act together to exacerbate inflammation in spinal cords

Cited by 195 publications

References 37 publications

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

Gut microbiome is associated with multiple sclerosis activity in children

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis‐Related Th17 Response by Host‐Microbe Retinoic Acid Biosynthesis

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