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.

Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice

“…This study also corroborated an earlier study that showed no change in the alpha diversity of the colonic mucosa-associated microbiota as a function of SDR10. Interestingly, these findings contrast sharply with previously published research that indicates that chronic restraint stress and water avoidance stress shift the alpha diversity of the colonic mucosa and distal ileum respectively3536. Restraint stress and SDR share downstream effects, including increases in anxiety-like behavior in exposed mice.…”

The commensal microbiota exacerbate infectious colitis in stressor-exposed mice

“…The Firmicutes are often associated with intestinal inflammation, and have been found to be elevated in mice with experimental colitis that are exposed to stress (Watanabe et al, 2016) as well as in humans with ulcerative colitis (Forbes et al, 2016). The Actinobacteria contain the beneficial bacterial genus Bifidobacterium , and interestingly the mean relative abundance of Bifidobacterium was different among the groups.…”

Disturbance in the Mucosa-Associated Commensal Bacteria Is Associated with the Exacerbation of Chronic Colitis by Repeated Psychological Stress; Is That the New Target of Probiotics?

“…We previously reported that the concentration of IgA and IgG in luminal contents of mice suffering from severe colitis was increased [ 25 ]. It was previously reported that certain gut microbiota are coated with IgG and IgA [ 36 ].…”

“…The sequences acquired from Miseq were analyzed using the Quantitative Insights Into Microbial Ecology (QIIME) software package version 1.8.0 [ 24 ]. All protocols were performed as previously reported [ 25 ]. Raw 250-bp paired-end sequence reads were combined, and quality filtering was performed [ 26 , 27 ].…”