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.