PDF(Pubmed)
Abstract：
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.
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.
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.
摘要：
背景：肠道菌群是调节宿主健康的关键因素，但是宿主对病原体的抗性差异与肠道微生物相互作用之间的关系尚不清楚。在这里，我们使用单细胞转录组学研究了仔猪肠道菌群与其抗病性之间的潜在相关性，16S扩增子测序，宏基因组学，和非靶向代谢组学。
结果：猪流行性腹泻病毒（PEDV）感染导致仔猪肠道菌群发生显著变化。值得注意的是,长白猪感染PEDV后很快失去抵抗力，但是将民猪的粪便微生物群移植到长白猪可以减轻感染状况。宏观基因组和动物保护模型确定肠微生物群中的罗伊氏乳杆菌和淀粉乳杆菌发挥抗感染作用。此外，次级胆汁酸（DCA）和石胆酸（LCA）的代谢组学筛选与罗伊氏乳杆菌和淀粉乳杆菌显着相关，但在动物模型中只有LCA发挥保护作用。此外,LCA补充改变了肠道T细胞群的分布，并导致显著富集的CD8+CTL，体内和体外实验表明，LCA通过FXR受体增加猪肠上皮细胞中SLA-I的表达，从而招募CD8+CTL发挥抗病毒作用。
结论：总体而言，我们的研究结果表明，肠道微生物群的多样性影响疾病的发展，操纵罗伊乳杆菌和淀粉乳杆菌，以及LCA，代表了改善仔猪PEDV感染的有希望的策略。视频摘要。
结果：猪流行性腹泻病毒（PEDV）感染导致仔猪肠道菌群发生显著变化。值得注意的是,长白猪感染PEDV后很快失去抵抗力，但是将民猪的粪便微生物群移植到长白猪可以减轻感染状况。宏观基因组和动物保护模型确定肠微生物群中的罗伊氏乳杆菌和淀粉乳杆菌发挥抗感染作用。此外，次级胆汁酸（DCA）和石胆酸（LCA）的代谢组学筛选与罗伊氏乳杆菌和淀粉乳杆菌显着相关，但在动物模型中只有LCA发挥保护作用。此外,LCA补充改变了肠道T细胞群的分布，并导致显著富集的CD8+CTL，体内和体外实验表明，LCA通过FXR受体增加猪肠上皮细胞中SLA-I的表达，从而招募CD8+CTL发挥抗病毒作用。
结论：总体而言，我们的研究结果表明，肠道微生物群的多样性影响疾病的发展，操纵罗伊乳杆菌和淀粉乳杆菌，以及LCA，代表了改善仔猪PEDV感染的有希望的策略。视频摘要。
