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

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

  • J Anim Sci Biotechnol. 2023 Jan 6;14(1):4. doi: 10.1186/s40104-022-00807-y.
Xinkai Wang 1 Yifan Hu 1 Xiaoyan Zhu 1 Liyuan Cai 1 Muhammad Zahid Farooq 1 2 Xianghua Yan 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
  • 2 Department of Animal Sciences, University of Veterinary and Animal Sciences (Jhang Campus), Lahore, 54000, Pakistan.
  • 3 State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China. xhyan@mail.hzau.edu.cn.
Abstract

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 development 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 regulating 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 antibody 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 (PIgR), B cell-activating factor of the TNF family (BAFF), and activation-induced cytidine deaminase (AID) in the duodenum. Additionally, Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/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.

Keywords

Bacteroides; Chicken; IgA; Intestinal health; Isovaleric acid; Macrophage.

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