Psychological stress disrupts intestinal epithelial cell function and mucosal integrity through microbe and...

Area of Science:

• Microbiology
• Neuroscience
• Gastroenterology

Background:

• Psychological stress negatively impacts gut health, increasing risks for enteric infections and chronic bowel diseases.
• Intestinal epithelial cells (IECs) are crucial for maintaining a balanced gut environment and host-microbe interactions.

Purpose of the Study:

• To investigate how social stress affects colonic IECs, the mucosal layer, and gut microbiota in mice.
• To determine if disruption of colonic IECs is a key factor in stress-induced intestinal dysfunction.

Main Methods:

• Conventionally raised (CONV-R) and germ-free (GF) mice were subjected to social disruption stress (Str).
• RNA sequencing was used to analyze transcriptional changes in colonic IECs.
• Microbiome composition and function were assessed alongside mucosal integrity and microbial translocation.

Main Results:

• Stress induced pro-inflammatory, pro-oxidative, and antimicrobial gene expression in CONV-R mice's IECs, alongside mucus thinning and microbial translocation.
• IECs from GF mice showed no transcriptional changes upon stress but exhibited primed oxidative responses to bacterial challenge.
• Stress-induced oxidative enzymes (Duox2, Nos2) in CONV-R mice correlated with microbiome alterations, suggesting ROS mediates gut dysbiosis.

Conclusions:

• Social stress disrupts colonic epithelial and mucosal integrity in a microbiota-dependent manner.
• Host stress signals and an intact microbiota are essential for stress-induced gut pathology.
• These findings offer insights into stress-related bowel diseases in humans.