Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets

肠道微生物衍生的 LCA 介导仔猪 PEDV 感染的保护作用

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作者:Jun-Hong Xing, Tian-Ming Niu, Bo-Shi Zou, Gui-Lian Yang, Chun-Wei Shi, Qing-Song Yan, Ming-Jie Sun, Tong Yu, Shu-Min Zhang, Xi-Ze Feng, Shu-Hui Fan, Hai-Bin Huang, Jun-Hong Wang, Ming-Han Li, Yan-Long Jiang, Jian-Zhong Wang, Xin Cao, Nan Wang, Yan Zeng, Jing-Tao Hu, Di Zhang, Wu-Sheng Sun, Wen-Tao Y

Background

The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics.

Conclusions

Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.

Results

Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. Conclusions: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.

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