Effect of Chronic Social Defeat Stress on the Small-Intestinal Environment, Including the Gut Flora, Immune System, and Mucosal Barrier Integrity

TL;DR

Chronic stress in mice leads to gut flora changes, weakened intestinal barriers, and inflammation, linking psychological stress to gut health issues.

Contribution

This study reveals how chronic social defeat stress affects small-intestinal flora, immune response, and barrier integrity in mice.

Findings

CSDS mice showed altered gut microbiome with increased Pseudomonadota and Patescibacteria.

CSDS mice had reduced Occludin, Claudin-4, and Regenerating gene IIIγ expression in the small intestine.

CSDS mice exhibited increased intestinal permeability and microinflammation marked by elevated IL-1β and macrophage activity.

Abstract

Psychological stress is deeply involved in the pathophysiology of gastrointestinal diseases. We investigated the effect of psychological stress on the small-intestinal environment, including gut flora, immune system, and mucosal integrity in mice subjected to chronic social defeat stress (CSDS). CSDS mice were established by exposing a C57BL/6N mouse to an ICR aggressor mouse. Stool samples were obtained to investigate its properties and the gut microbiome profile. Using small-intestinal tissues, the expression of cytokines, antimicrobial peptides, and tight junction proteins (TJPs) were examined by real-time RT-PCR and immunohistochemistry. Small-intestinal permeability was evaluated by transepithelial electrical resistance assay. For stool properties, mean Bristol scale score and fecal water content were significantly lower in the CSDS group. Pseudomonadota and Patescibacteria were significantly more abundant in the stools from CSDS mice. Among TJPs and antimicrobial peptides, the expression of Occludin, Claudin-4, and Regenerating gene IIIγ was significantly decreased in the small intestine epithelium of CSDS mice. The small-intestinal permeability was significantly increased in CSDS mice. Lipopolysaccharide immunoreactivity, the number of macrophages, and proinflammatory IL-1β expression were significantly increased in the small intestine of CSDS mice. These findings suggest that psychological stress is associated with mucosal barrier dysfunction and microinflammation in small-intestinal tissues.

Figures