Exploration Of Potential Probiotic Function Of Christensenella Minuta SJ

The close correlation between the gut microbiota and host health has been observed in a large number of gut metagenomic cohort studies,with the ability of the gut microbiota to modulate the host immune system,it plays an important role in the energy metabolism of host and the stabilization of intestinal microenvironment.Intestinal dysbacteriosis is an important feature of many metabolic diseases,such as diabetes,hypertension,arteriosclerosis,the use of prebiotics and probiotics to regulate the intestinal flora of patients to achieve therapeutic results is an important direction for the future treatment of metabolic diseases.However,the mechanisms underpinning host-microbe interactions in the gut are largely unknown.Christensenella minuta,an intestinal commensal microbe,has been found to regulate host metabolism by producing a new class of secondary cholic acids.First of all,this study confirmed that C.minuta can alleviate the disorder of glucose and lipid metabolism in Dio mice induced by high-fat diet,and significantly improve the liver injury in DIO mice induced by high-fat diet.Through the analysis of metabolite and expander of intestinal contents in DIO mice,it was found that the metabolite of intestinal contents in DIO mice changed after C.minuta administration,but the composition of intestinal microbes did not change much,this suggests that the therapeutic effect of intragastric administration of C.minuta in mice on a high-fat diet may be achieved by altering metabolites in the mice rather than by altering the gut microbiota of the host.It was found that the abundance of bile acids was changed in the metabolite analysis of mice.By analyzing the transformation activity of C.minuta cholic acid,it was found that C.minuta can transform cholic acid to produce a new class of bile acid derivatives,these cholic acid derivatives were identified as new 3-O-acylated secondary cholic acids by NMR analysis.Furthermore,through the DIO model animal experiment of butyryl cholic acid gastric perfusion,it is proved that the 3-O-acyl cholic acid gastric perfusion model animal can exert the same therapeutic effect as C.minuta gastric perfusion to improve the metabolic abnormality of the host;This suggests that C.minuta may exert therapeutic effects by transforming 3-O-acylcholic acid.Finally,population cohort studies demonstrate that 3-O-acylcholic acid is widely distributed in the population but significantly reduced in patients with type 2 diabetes,a finding that is also consistent with a reduction in C.minuta in patients with type 2diabetes.In this study,we studied the physiological function of C.minuta in Dio mice based on animal model and in vitro,and found the therapeutic effect of C.minuta on metabolic disorder and liver inflammation in DIO mice,C.minuta produced a new class of 3-O acylation substituted secondary cholic acids,which could alleviate metabolic abnormalities as C.minuta did in animal models of gastric disease alone,it is hypothesized that C.minuta can regulate host metabolism by producing3-O-acylcholic acid and improve host health.This study lays a foundation for the application of C.minuta and acylated cholic acid in the treatment of type II diabetes and other metabolic diseases.