Effect Of Intermittent Fasting On Ulcerative Colitis And Behavior Disorders In Mice

With the rapid development of social economy and the prevalence of the westernization of Chinese people's diet,the incidence of many inflammation-related diseases has shown an increasing trend year by year.Among them,ulcerative colitis(UC)is a kind of inflammatory bowel disease,and its pathogenesis is currently unclear.However,the widely accepted potential pathogenic factors of UC mainly involve genetics,environment,intestinal flora disorders and immune response.In addition,many patients with UC are clinically accompanied by anxiety and depression-like behaviors.These mood disorders have been increasingly recognized as important comorbidities of UC.Based on the current characteristics of UC that are difficult to cure and easy to relapse,it is of great significance to explore a new type of diet with intestinal protection.Intermittent fasting(IF)mainly includes alternate-day fasting(ADF),time-restricted feeding(TRF)and intermittent energy restriction(IER).A large number of studies have shown that IF has the effects of anti-inflammatory,remodeling the intestinal flora,improving obesity and prolonging lifespan.However,the influence of IF on the occurrence and development of UC and the accompanying anxiety and depression-like behaviors is rarely reported.Therefore,this study used DSS to establish a mouse model of ulcerative colitis,and explored whether the three intermittent fasting modes can improve the intestinal flora of mice with ulcerative colitis and thereby alleviate a series of pathological features of UC and its Concomitant anxiety and depression-like behavior.This study aims to explore the overall impact of colitis-related disorders in the three intermittent fasting modes,and has positive research significance.The main research contents are as follows:(1)In order to study the effects of different intermittent fasting patterns on the intestinal barrier and intestinal inflammation in mice with colitis,8 weeks old C57BL/6J male mice were used as the research object,and 2% DSS aqueous solution was used instead of small mice.Mouse drinking water to construct a mouse model of ulcerative colitis.Three different dietary interventions were carried out throughout the whole process,namely ADF with fasting every other day,TRF with 8 hours of diet restriction every day,and two 4-day IER cycles.It was found that TRF and IER intervention significantly improved the colon shortening of colitis mice,and reduced the DAI score and mortality.The histopathological results of the colon showed that the intestinal barrier damage and inflammatory cell infiltration of mice were reduced after the intervention of TRF and IER,but the ADF fasting mode did not see the above improvement.At the same time,after the intervention of TRF and IER,the number of goblet cells and the number of crypts in the mucus layer of the mouse colon increased significantly,and the m RNA expression level of MUC2 was significantly up-regulated.It also reduced the damage of the colonic tight junction and increased the tight junction protein Claudin-1.The m RNA expression of Occludin and Zo-1.In addition,TRF and IER intervention also significantly down-regulated the levels of TNF-?,IL-1? and MDA,a biomarker of oxidative stress,in the colon tissue of mice with colitis.(2)The effects of different intermittent fasting patterns on the anxiety-and-compulsive behaviors of colitis mice were explored.The elevated plus maze test and the bead-embedded test were used to evaluate the behavioral disorders of ulcerative colitis mice.The results showed that TRF and IER intervention significantly improved the behavioral disorders of mice,increased the 5-HT content in the serum of colitis mice,decreased the LPS content in the serum,and inhibited the excessive microglia in the brains of colitis mice.Activation and neuronal damage.In addition,in the brain tissues of colitis mice,TRF and IER intervention also significantly inhibited the m RNA expression of inflammatory cytokines such as TNF-?,IL-1? and IL-6,reduced the levels of MDA and GSSG in the brain tissue,and also improved the level of GSH.(3)Using 16 S rDNA sequencing technology and GC technology to analyze the changes of the intestinal flora structure and metabolite SCFAs of colitis mice.Studies have found that TRF and IER intervention can improve the decrease in the species richness of intestinal flora in colitis mice to a certain extent,and inhibit the abundance of intestinal inflammation-related bacteria(Shigella,Escherichia coli,etc.)in mice with ulcerative colitis.Increase,and ADF intervention does not have the above-mentioned beneficial effects.In addition,TRF and IER intervention also significantly increased the content of acetic acid,butyric acid and isobutyric acid in the stool of mice with colitis,and promoted the abundance of short-chain fatty acid producing bacteria(Lactobacillus,Coprococcus,etc.).Through correlation analysis,it was found that butyric acid showed a significant negative correlation with related indexes of ulcerative colitis such as DAI index and colon histology score.And there is a significant positive correlation with the proportion of mice entering the open arm in the elevated maze test,and a significant negative correlation with the number of beads buried in the bead test.In summary,TRF and IER have a protective effect on colitis and related behavioral disorders.Part of the reason may be to improve the composition of intestinal microbes and increase the production of beneficial metabolites SCFAs,thereby reducing the damage to the intestinal barrier,thereby inhibiting the colon and Inflammation and oxidative damage of the brain.Therefore,a reasonable IF program is an effective nutritional intervention strategy to prevent and improve colitis.