Dataset Information

Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.

ABSTRACT: The effect of psychological stress on the gastrointestinal microbiota is widely recognized. Chronic psychological stress may be associated with increased disease activity in inflammatory bowel disease, but the relationships among psychological stress, the gastrointestinal microbiota, and the severity of colitis is not yet fully understood. Here, we examined the impact of 12-week repeated water-avoidance stress on the microbiota of two inbred strains of T cell receptor alpha chain gene knockout mouse (background, BALB/c and C57BL/6) by means of next-generation sequencing of bacterial 16S rRNA genes. In both mouse strains, knockout of the T cell receptor alpha chain gene caused a loss of gastrointestinal microbial diversity and stability. Chronic exposure to repeated water-avoidance stress markedly altered the composition of the colonic microbiota of C57BL/6 mice, but not of BALB/c mice. In C57BL/6 mice, the relative abundance of genus Clostridium, some members of which produce the toxin phospholipase C, was increased, which was weakly positively associated with colitis severity, suggesting that expansion of specific populations of indigenous pathogens may be involved in the exacerbation of colitis. However, we also found that colitis was not exacerbated in mice with a relatively diverse microbiota even if their colonic microbiota contained an expanded phospholipase C-producing Clostridium population. Exposure to chronic stress also altered the concentration of free immunoglobulin A in colonic contents, which may be related to both the loss of bacterial diversity in the colonic microbiota and the severity of the colitis exacerbation. Together, these results suggest that long-term exposure to psychological stress induces dysbiosis in the immunodeficient mouse in a strain-specific manner and also that alteration of microbial diversity, which may be related to an altered pattern of immunoglobulin secretion in the gastrointestinal tract, might play a crucial role in the development of chronic stress-induced colitis.

SUBMITTER: Watanabe Y

PROVIDER: S-EPMC4780833 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.

Watanabe Yohei Y Arase Sohei S Nagaoka Noriko N Kawai Mitsuhisa M Matsumoto Satoshi S

PloS one 20160307 3

The effect of psychological stress on the gastrointestinal microbiota is widely recognized. Chronic psychological stress may be associated with increased disease activity in inflammatory bowel disease, but the relationships among psychological stress, the gastrointestinal microbiota, and the severity of colitis is not yet fully understood. Here, we examined the impact of 12-week repeated water-avoidance stress on the microbiota of two inbred strains of T cell receptor alpha chain gene knockout m ...[more]

PMID: 26950850

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Project description:BackgroundUnderstanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.ResultsOur study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10-/- mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10-/- mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10-/- host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10-/- mice than the distinct microbiota reassembled in non-inflamed WT hosts.ConclusionsOur findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.

Project description:Inflammatory bowel diseases (IBDs) are chronic intestinal diseases, frequently associated with comorbid psychological and cognitive deficits. These neuropsychiatric effects include anxiety, depression, and memory impairments that can be seen both during active disease and following remission and are more frequently seen in pediatric patients. The mechanism(s) through which these extraintestinal deficits develop remain unknown, and the study of these phenomenon is hampered by a lack of murine pediatric IBD models. Herein we describe microbiota-gut-brain (MGB) axis deficits following induction of colitis in a pediatric setting. Acute colitis was induced by administration of 2% dextran sodium sulfate (DSS) for 5 days starting at weaning [postnatal day (P)21] causing reduced weight gain, colonic shortening, and colonic inflammation by 8 days post-DSS (P29), which were mostly resolved in adult (P56) mice. Despite resolution of acute disease, cognitive deficits (novel object recognition task) and anxiety-like behavior (light/dark box) were identified in the absence of changes in exploratory behavior (open field test) in P56 mice previously treated with DSS at weaning. Behavioral deficits were found in conjunction with neuroinflammation, decreased neurogenesis, and altered expression of pattern recognition receptor genes in the hippocampus. Additionally, persistent alterations in the gut microbiota composition were observed at P56, including reduced butyrate-producing species. Taken together, these results describe for the first time the presence of MGB axis deficits following induction of colitis at weaning, which persist in adulthood.NEW & NOTEWORTHY Here we describe long-lasting impacts on the microbiota-gut-brain (MGB) axis following administration of low-dose dextran sodium sulfate (DSS) to weaning mice (P21), including gut dysbiosis, colonic inflammation, and brain/behavioral deficits in adulthood (P56). Early-life DSS leads to acute colonic inflammation, similar to adult mice; however, it results in long-lasting deficits in the MGB axis in adulthood (P56), in contrast to the transient deficits seen in adult DSS. This model highlights the unique features of pediatric inflammatory bowel disease.

Dataset Information

Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.

Publications

Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.

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