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Bacteroides-derived isovaleric acid enhances mucosal immunity by facilitating intestinal IgA response in broilers

摘要Background:The interaction between nutrition and immunity plays a vital role in nutrient digestion,absorption,and metabolism during poultry production.Recent studies showed that the gut microbiota contributes to the develop-ment of intestinal mucosal immunity.However,the mechanisms by which gut microbes regulate this process remain unclear.Methods:We compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers(AA(lower mucosal immunity)and Chinese native Wuliang Mountain Black-bone chickens(WLMB)(higher mucosal immunity)using 16S rDNA sequencing,transcriptomic analysis,and immunoglobulin A(IgA)antibody repertoire sequencing.We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production.Next,we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity.Finally,we verified the function of candidate microbial metabolites in regu-lating the immune function of macrophages and the intestinal-epithelial cells(IECs)using in vitro experiments.Results:WLMB performs stronger mucosal immunity than AA,including higher IgA levels,more diverse IgA anti-body repertoire,and higher bacterial affinity.Bacteroides was identified as the key microbes related to the intestinal IgA response.Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA,polymeric immunoglobin receptor(PlgR),B cell-activating factor of the TNF family(BAFF),and activation-induced cytidine deaminase(AID)in the duodenum.Additionally,Bacteroides-derived isovaleric acid pro-moted M2 macrophage polarization of macrophage via mTOR/PPAR-y/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines,including interleukin(IL)-10,IL-4,BAFF,and transforming growth factor-beta(TGF-β),thus promoting IgA production in B cells by facilitating AID expression.Conclusion:Our study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers.Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing next-generation probiotics for broiler production.

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作者 Xinkai Wang [1] Yifan Hu [1] Xiaoyan Zhu [1] Liyuan Cai [1] Muhammad Zahid Farooq [2] Xianghua Yan [1] 学术成果认领
作者单位 State Key Laboratory of Agricultural Microbiology,Hubei Hongshan Labora-tory,Frontiers Science Center for Animal Breeding and Sustainable Production,College of Animal Sciences and Technology,Huazhong Agricultural University,Wuhan 430070,Hubei,China [1] State Key Laboratory of Agricultural Microbiology,Hubei Hongshan Labora-tory,Frontiers Science Center for Animal Breeding and Sustainable Production,College of Animal Sciences and Technology,Huazhong Agricultural University,Wuhan 430070,Hubei,China;Department of Animal Sciences,University of Veterinary and Animal Sciences(Jhang Campus),Lahore 54000,Pakistan [2]
发布时间 2023-06-25
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