Chronic Stress Induced Metabolic Disorder Of Gut Microbiota In Rats

Objectives: Chronic stress leads to the occurrence and development of multiple psychological and physiological diseases,gut microbiota is the significant carrier for the interaction between body and environment,the neural network system of intestine is also called the "second brain".The signals from gut can be effectively transmitted to the brain,causing psychological and physiological reactions in the body.We established chronic unpredictable mild stress(CUMS)model and chronic pain stress(SNI)model to study the changes of microbial diversity and abundance in small and large intestine,the changes of the short-chain fatty acids and gut neuropeptides GLP-1 and PYY,then further determine the mechanism of gut microbes in chronic stress.Methods: Male Sprague-Dawley rats were randomly divided into four groups,including control group,chronic unpredictable mild psychological stress group,sham group and chronic neuropathic pain stress group.The statistics of rats,containing body weight,open field,and mechanical pain threshold,were collected to confirm the success of modeling.The microbial diversity and abundance of gut feces were detected by 16 S rDNA sequencing.The changes of short-chain fatty acids in rat gut feces were analyzed by gas chromatography,and the changes of neuropeptides GLP-1 and PYY in the colon of rats were detected by immunohistochemistry.Results:(1)Chronic psychological stress and chronic pain stress induced different changes of gut microbiota between caecum and colon.In caecum,the relative abundance of Oscillospira significantly decreased,while the relative abundance of Sutterella markedly increased in colon.However,there were similar changes of gut microbiota between caecum and colon under chronic pain stress.The relative abundance of Lachnospiraceae and Ruminococcaceae descended not only in caecum but in colon.(2)In caecum,short-chain fatty acids had no significant change after chronic psychological stress.While the butyric acid decreased observably from colon under chronic psychological stress.Furthermore,the chronic unpredictable mild psychological stress and chronic neuropathic pain stress caused reduction of butyric acid in colon,and the acetic acid from colon also declined by chronic pain stress.(3)There was no obvious effect of chronic psychological stress and chronic pain stress on GLP-1 and PYY in colon.Conclusions: First,we found that chronic psychological stress and chronic pain stress led to changes of gut microbiota in rats.However,the effects of psychological stress and physiological stress on gut microbiota in rats were not consistent,that is to say,the effects of different types of stressors on intestinal tract were specific.Second,at the phyla level,there was a significant difference in the relative abundance of fecal microbe between psychological stress and pain stress in rats.There was a trend for the psychological stress rats to have higher bacteria in the Firmicutes phylum in cecum while the pain stress rats have higher bacteria in the Bacteroides phylum,which further validated the hypothesis that the intestinal tract had a specific response to different stressors.Third,the effects of psychological stress and physiological stress on the intestinal tract of rats were mainly concentrated in the cecum and colon.Fourth,the mechanism of changes in intestinal microbe induced by chronic psychological stress and chronic pain stress was related to the role of short-chain fatty acids,both of which have inhibitory effects on colonic butyric acid.Butyric acid could be used as the potential basis for evaluating stress level.Fifth,the results showed that there was no change in gastrointestinal peptide GLP-1 and PYY in the colon after chronic psychological stress and chronic pain stress in rats,indicating that chronic psychological and pain stress were not related to GLP-1 and PYY.