| Diarrhea caused by early weaning during intensive lamb rearing is a highly prevalent and widespread animal disease with high mortality affecting animal production.In previous treatments,the use of pharmaceutical antibiotics has led to a large increase in drug residues and the emergence of super-resistant bacteria,which have become a new public health problem.Therefore,the development of new antimicrobial tools is essential to address the problem of antibiotic "dependence".Bacteroides uniformis is the most abundant core strain in mammals,regulates animal intestinal homeostasis,and is considered a next-generation probiotic(NGP)candidate.However,the key metabolites and mechanisms by which B.uniformis treats intestinal inflammation in animals are unknown.In this study,a strain of B.uniformis JCM5828 of sheep origin was isolated and molecularly biologically characterized as B.uniformis JCM5828.We investigated the molecular mechanism of B.uniformis-mediated intestinal microecological changes and its metabolites as immune signaling molecules to alleviate the occurrence of colonic inflammation.The experimental results are as follows:(1)A strain of B.uniformis of sheep origin,named B.uniformis JCM5828,was screened,isolated and identified from healthy sheep feces using xylan as a single carbon source,and was found to be extremely bile salt tolerant in vitro.We speculate that this strain may be involved in the regulation of bile acid metabolism in the host intestine.(2)B.uniformis JCM5828 gavage greatly alleviated the development of DSS-induced colitis in mice and restored the mechanical and immune barriers of the colon.In addition,increased abundance of B.uniformis in the colon promoted the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis and inhibited the ecological niche of Escherichia Shigella,thereby regulating intestinal lipid metabolism function.Specifically,B.uniformis significantly increased the biosynthesis of primary and secondary bile acids alpha-Muricholic acid(α-MCA),Isochenodeoxycholic acid(iso CDCA),hyodeoxycholic acid(HDCA),and isolithocholic acid(isoLCA)in colonic contents and regulated the expression of key genes and proteins of the IL-17 signaling pathway in colonic tissues and inhibited TH17 cell differentiation.In vitro cellular validation showed that a single strain of B.uniformis failed to inhibit TH17 cell differentiation.Instead,its key metabolites α-MCA,HDCA and isoLCA are the targets that inhibit TH17 cell differentiation and thus modulate the intestinal immune response.(3)The effect of B.uniformis JCM5828 gavage on diarrhea in lambs was further confirmed by measuring serum inflammatory factors and gene expression levels of intestinal barrier proteins in ETEC-induced diarrheic lake lambs.The results showed that B.uniformis greatly alleviated the development of ETEC-induced colitis,significantly increased the daily weight gain of diarrheic lambs(P < 0.05),significantly reduced the diarrhea index score and serum pro-inflammatory factor expression levels(P < 0.05),and restored the mechanical and immune barriers of the colon.In summary,this study was conducted in a chemically induced mouse colitis model and a bacterially infected lamb colitis model,and initially revealed the mechanism of action of B.uniformis as a potential probiotic strain that regulates the intestinal microecological structure to exert probiotic functions,and screened to obtain target metabolites with anti-inflammatory functions,providing available green additives with potential replacement functions.We also screened and obtained target metabolites with anti-inflammatory function,which can be used for the development of new green additives with potential antibiotic function. |
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