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.
Highlights
Recent advances in DNA sequencing technology have revealed that several hundred species of bacteria colonize the human gastrointestinal (GI) tract [1]
We compared the community structures of the colonic microbiota of T cell receptor alpha chain gene (Tcra)−/+ mice (B/c-heterozygous mice not exposed to rWAS (HET); n = 5) and of Tcra−/− mice (B/c-CON; n = 5) not exposed to repeated water-avoidance stress (rWAS) and found that the relative abundances of several bacterial genera were lower in the colonic microbiota of B/c-CON mice compared with that in B/c-HET mice (Fig 1A), but these decreases were not statistically significant (FDR-corrected P value = 0.09)
We investigated the impact of rWAS on the community structures of the colonic microbiota of B/c mice exposed to low- or high-frequency rWAS (LFW, n = 4; HFW, n = 5)
Summary
Recent advances in DNA sequencing technology have revealed that several hundred species of bacteria colonize the human gastrointestinal (GI) tract [1]. The roles of the GI microbiota in various diseases has been widely recognized, such as colorectal cancer [3], type 1 diabetes [4], obesity [5], and inflammatory bowel disease (IBD) [6]. IBD (Crohn’s disease and ulcerative colitis) is a complex chronic inflammatory disorder of the GI tract that is a major public health problem in many countries [7]. HET, Tcra−/+ mice not exposed to repeated water-avoidance stress (rWAS); CON, Tcra−/− mice not exposed to rWAS; LFW, Tcra−/− mice exposed to low-frequency (1 day) rWAS; HFW, Tcra−/− mice exposed to high-frequency (5 days) rWAS; RES, Tcra−/− mice resistant to rWAS-induced colitis; SEN, Tcra−/− mice sensitive to rWAS-induced colitis. Large population of C. perfringens, several had a lower histological score than the others and were found to have a phylogenetically diverse microbiota.
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