Effect of chronic restraint stress and western‐diet feeding on colonic regulatory gene expression in mice

Abstract

Background Diet‐induced obesity (DIO) and psychological stress are significant independent regulators of gastrointestinal physiology; however, our understanding of how these two disorders influence the host‐microbe interface is still poorly characterized. The aim of this study was to assess the combined influences of diet‐induced obesity and psychological stress on microbiome composition and colonic gene expression. Methods C57BL/6J mice (n = 48) were subject to a combination of 22 weeks of Western diet (WD) feeding and a chronic restraint stressor (CRS) for the last 4 weeks of feeding. At the end of the combined intervention, microbiome composition was determined from cecal contents, and colonic tissue gene expression was assessed by multiplex analysis using NanoString nCounter System and real‐time qPCR. Results WD feeding induced a DIO phenotype with increased body weight, worsened metabolic markers, and alterations to microbiome composition. CRS reduced body weight in both dietary groups while having differential effects on glucose metabolism. CRS improved the Firmicutes/Bacteroidetes ratio in WD‐fed animals while expanding the Proteobacteria phyla. Significantly lower expression of colonic Tlr4 (p = 0.008), Ocln (p = 0.004), and Cldn3 (p = 0.004) were noted in WD‐fed animals compared to controls with no synergistic effects observed when combined with CRS. No changes to colonic expression of downstream inflammatory mediators were observed. Interestingly, higher levels of expression of Cldn2 (p = 0.04) and bile acid receptor Nr1h4 (p = 0.02) were seen in mice exposed to CRS. Conclusion Differential but not synergistic effects of WD and CRS were noted at the host‐microbe interface suggesting multifactorial responses that require further investigation.

The Effects of Stress and Diet on the “Brain–Gut” and “Gut–Brain” Pathways in Animal Models of Stress and Depression

“…Interestingly, the composition of the gut microbiota in unstressed female mice fed a high fat diet has been shown to resemble that of female mice exposed to CUMS, but fed a standard diet; however, the same effect is not observed in males, thus females may be more susceptible to the potential negative effects of high fat diets on the gut-brain axis [93]. Hatton-Jones et al [111] showed a Western diet decreased colonic tight junction protein expression in male mice, but this did not result in increased depressive-like behaviour and these effects were not synergistic with those of CRS. Yet, Ranyah Shaker et al [148] demonstrated male Wistar rats fed a high-fat diet had increased dopamine and glutamate, but decreased serotonin in the brain, with increased circulating IL-6 in association with decreased Clostridium and Bacteroides abundance.…”