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

Abstract

Background Depression often coexists with the irritable bowel syndrome (IBS) which is characterized by alterations in gut function. There is emerging evidence that the microbial composition (microbiota) of the gut is altered in IBS, but the basis for this is poorly understood. The aim of this study was to determine whether the induction of chronic depression results in changes in the colonic function and in its microbial community, and to explore underlying mechanisms.Methods Bilateral olfactory bulbectomy (OBx) was used to induce depression-like behavior in mice. Colonic function was assessed by measuring muscle contractility, pellet excretion, c-fos activity, and serotonin levels. Microbiota profiles were obtained using denaturing gradient gel electrophoresis (DGGE). The hypothalamic-pituitary axis (HPA) was assessed by the hypothalamic expression of corticotropin-releasing hormone (CRH). In separate studies, mice without OBx received CRH via intracerebroventricular (ICV) infusion for 4 weeks prior to assessing colonic function and microbiota profiles.Key Results Olfactory bulbectomy mice demonstrated chronic depression- and anxiety-like behaviors associated with elevated central CRH expression and increases in c-Fos activity, serotonin levels, and motility in the colon. These changes were accompanied by an altered intestinal microbial profile. Central CRH administration produced similar changes in behavior and motility and altered the microbiota profile in the colon.Conclusions & Inferences The induction of chronic depression alters motor activity and the microbial profile in the colon likely via activation of the HPA. These findings provide a basis for linking the behavioral and gastrointestinal manifestations of IBS.

The structures of the colonic mucosa-associated and luminal microbial communities are distinct and differentially affected by a prolonged murine stressor

“…However, immunomodulation is not the only way in which stressor exposure may impact the composition of the gut microbiota. In an olfactory bulbectomy model of stressor sensitization, Park et al (2013) demonstrated that stressor-induced increases in colonic motility impact microbiota structure through a corticotrophin-releasing hormone (CRH)-dependent mechanism. 85 Because CRH-induced alterations in colonic motility can be disrupted by cutting the vagal nerve 86 , and because the vagus nerve is considered a primary route through which the brain and gut microbiota interact [87][88][89] , it is possible that the observed stressorinduced changes in the colonic microbiota are vagally-mediated.…”

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

“…107,108 These data however, have not been validated in patients with depression. In one study on human subjects with depression, no significant difference in the composition of gut microbiota was found between depressed patients and a control group.…”

Commensal Bugs from the Gut-Shaping Human Health and Disease

“…It has been reported that chronic depression is associated with a distorted microbial composition and colonic motility in mice [151]. Interestingly it has also been reported that chronic gastrointestinal inflammation can actually induce anxiety-like behavior and modify the central nervous system biochemistry [147,152].…”