Effect And Mechanism Of Taurine On Reconstitution And Restoration Of Gut Microbiota Homeostasis

Taurine is a free amino acid that is abundant in mammalian bodies.It can be synthesized in vivo from cysteine and methionine through the consecutive catalysis of cysteine dioxygenase and cysteine sulfinate acid decarboxylase.However,the endogenous synthesis of taurine is generally low in most organisms,making dietary supplementation an important way to maintain its stable content in the body.Recent studies have suggested that taurine holds potential in regulating gut function and homeostasis,and its association with gut microbiota dysbiosis in disrupted gut homeostasis has been observed.However,existing research primarily focuses on the direct effects of taurine on the body and the observation of microbiota changes,without a consistent determination of taurine’s specific regulatory effects on gut microbiota abundance and function.Furthermore,the mechanism by which taurine regulates gut microbiota homeostasis requires further clarification.In this study,we investigated the effects of taurine supplementation on gut microbiota homeostasis and metabolites in healthy mice,and then evaluated the regulatory effects of taurine on gut microbiota homeostasis and functional recovery in a mouse model of gut dysbiosis.Finally,we explored the mechanism of taurine regulation of gut microbiota homeostasis from the perspectives of dose-effect relationship,host bile acid metabolism,and gut microbiota metabolic function,providing a theoretical basis for targeted modulation of gut microbiota and promotion of microbiota homeostasis.The main research results are as follows:Firstly,the effects of taurine supplementation on gut microbiota and physiological status of healthy mice were investigated by providing taurine in drinking water.The results showed that taurine supplementation did not alter the histopathological structure of the mouse intestinal tissue,but it did change the composition and diversity of gut microbiota and increase Observed Species index.Specifically,the abundance of Bifidobacterium,Bilophila,as well as Ruminococcaceae and Lachnospiraceae increased.Metabolomic analysis of feces showed that taurine supplementation altered gut microbiota metabolites,with significant increases in taurine,taurodeoxycholic acid(TDCA),acamprosate,and taurocholic acid(TCA).Next,two gut microbiota dysbiosis models were established in mice by using antibiotic cocktail and Citrobacter rodentium,and the regulatory effect of taurine supplementation on dysbiotic gut microbiota and related physiological indicators was evaluated.The experimental results showed that supplementation of taurine could increase the abundance of beneficial bacteria such as Lactobacillus,regulate the severely disrupted gut microbiota,and reverse the decrease of colonic cytokine levels caused by antibiotics,thereby restoring intestinal immune function.In addition,in C.rodentium-infected mice,compared with the C.R group,taurine supplementation increased the shannon index and evenness index by 1.19 and 1.13 times,respectively,significantly changed the β-diversity of gut microbiota,decreased weight loss caused by pathogen infection,reduced the load of C.rodentium in mouse feces,and enhanced the host’s colonization resistance to pathogenic bacteria during the susceptible period after antibiotic treatment.Based on the results mentioned above,this study further investigated the mechanism of taurine supplementation in regulating gut homeostasis in mice using the antibiotic model with low(1%),medium(2.5%),and high(5%)doses of taurine supplementation provided in drinking water.The results showed that the effect of taurine supplementation on gut microbiota homeostasis and function restoration was dose-dependent.The level of taurine in the colon contents showed a positive correlation with the supplementation dosage.Different doses of taurine supplementation had different effects on the restoration of gut immune function and microbial metabolic function.Low-dose taurine supplementation had the most significant effect on improving gut immune function,while medium-dose taurine supplementation was more effective in restoring short-chain fatty acid levels in the cecum of mice.In addition,changes in the bile acid composition in the liver and colon of mice indicated that taurine supplementation promoted bile acid synthesis and transformation into taurine-conjugated state in the liver.Low and medium-dose taurine supplementation helped to restore the secondary bile acid metabolic function in the colon of mice,increasing the levels of secondary bile acids,and medium-dose supplementation made the bile acid composition closer to the Con.group.In terms of gut microbiota restoration,medium-dose taurine supplementation significantly increased the shannon and richness index after 14 days of restoration,gradually restoring the α-diversity loss caused by antibiotics and making the gut microbiota structure closer to the Con.group.Through functional gene analysis of gut microbiota,it was found that medium-dose taurine supplementation upregulated taurine and histidine metabolism,primary and secondary bile acid biosynthesis,and fatty acid biosynthesis.The differential metabolites analysis of fecal metabolites between medium-dose taurine supplementation group and Anti.group detected 51 differential metabolites,which were consistent with the results of the gut microbiota functional gene analysis,focusing on the taurine and bile acid metabolism pathways.Based on the above research,this study determined that taurine can regulate gut microbiota and promote the reshaping of the dysbiotic gut microbiota and restoration of its function in the animal model.The restoration effect shows a dose-dependent relationship,with the optimal effect observed at a medium dose of taurine supplementation.Taurine is ingested by the mice through drinking water,alters bile acid synthesis and metabolism,increases taurine-conjugated bile acid content,enriches relevant taxa in the colon,thereby regulating gut microbiota composition,enhancing taurine and bile acid-related metabolic function,restoring gut immune levels,and improving metabolic and gut microbiota dysbiosis.