Altered colonic function and microbiota profile in a mouse model of chronic depression

Area of Science:

• Neurogastroenterology
• Microbiome research
• Psychiatry

Background:

• Irritable bowel syndrome (IBS) frequently co-occurs with depression, featuring altered gut function.
• The gut microbiota's role in IBS pathogenesis is under investigation.
• The basis for gut dysbiosis in IBS remains poorly understood.

Purpose of the Study:

• To investigate if induced chronic depression alters colonic function and microbial community in mice.
• To explore the underlying mechanisms connecting depression and gut changes.

Main Methods:

• Depression-like behavior induced via bilateral olfactory bulbectomy (OBx) in mice.
• Colonic function assessed by muscle contractility, pellet excretion, c-fos activity, and serotonin.
• Microbiota profiling via denaturing gradient gel electrophoresis (DGGE); Hypothalamic-pituitary-adrenal (HPA) axis assessed via corticotropin-releasing hormone (CRH) expression.
• CRH administration in non-OBx mice to evaluate its direct effects.

Main Results:

• OBx mice exhibited depression/anxiety behaviors, elevated central CRH, increased colonic c-Fos activity, serotonin, and motility.
• Significant alterations in the intestinal microbial profile were observed in OBx mice.
• Central CRH administration mimicked behavioral and motility changes and altered colonic microbiota.

Conclusions:

• Induced chronic depression modifies colonic motor activity and microbial composition, primarily through HPA axis activation.
• These findings establish a link between behavioral and gastrointestinal symptoms in IBS.
• The study provides a mechanistic basis for the gut-brain axis in depression and IBS.