Xing JunHong, Niu TianMing, Yu Tong, Zou BoShi, Shi ChunWei, Wang YingJie, Fan ShuHui, Li MingHan, Bao MeiYing, Sun Yu, Gao KuiPeng, Qiu JingJing, Zhang DongXing, Wang Nan, Jiang YanLong, Huang HaiBin, Cao Xin, Zeng Yan, Wang JianZhong, Zhang ShuMin, Hu JingTao, Zhang Di, Sun WuSheng, Yang GuiLian, Yang WenTao, Wang ChunFeng
College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, 2888 Xincheng Street, Changchun, 130118, China.
Microbiome. 2025 Apr 2;13(1):90. doi: 10.1186/s40168-025-02078-x.
The Porcine Epidemic Diarrhea Virus (PEDV) is one of the major challenges facing the global pig farming industry, and vaccines and treatments have proven difficult in controlling its spread. Faecalibacterium prausnitzii (F.prausnitzii), a key commensal bacterium in the gut, has been recognized as a promising candidate for next-generation probiotics due to its potential wide-ranging health benefits. A decrease in F.prausnitzii abundance has been associated with certain viral infections, suggesting its potential application in preventing intestinal viral infections. In this study, we utilized a piglet model to examine the potential role of F.prausnitzii in PEDV infections.
A piglet model of PEDV infection was established and supplemented with F.prausnitzii, revealing that F.prausnitzii mitigated PEDV infection. Further studies found that outer membrane vesicles (OMVs) are the main functional components of F.prausnitzii, and proteomics, untargeted metabolomics, and small RNA-seq were used to analyze the composition of OMVs. Exhaustion of the gut microbiota demonstrated that the function of Fp. OMVs relies on the presence of the gut microbiota. Additionally, metagenomic analysis indicated that Fp. OMVs altered the gut microbiota composition, enhancing the abundance of Faecalibacterium prausnitzii, Prevotellamassilia timonensis, and Limosilactobacillus reuteri. Untargeted metabolomics analysis showed that Fp. OMVs increased phosphatidylcholine (PC) levels, with PC identified as a key metabolite in alleviating PEDV infection. Single-cell sequencing revealed that PC altered the relative abundance of intestinal cells, increased the number of intestinal epithelial cells, and reduced necroptosis in target cells. PC treatment in infected IPEC-J2 and Vero cells alleviated necroptosis and reduced the activation of the RIPK1-RIPK3-MLKL signaling axis, thereby improving PEDV infection.
F.prausnitzii and its OMVs play a critical role in mitigating PEDV infections. These findings provide a promising strategy to ameliorate PEDV infection in piglets. Video Abstract.
猪流行性腹泻病毒（PEDV）是全球养猪业面临的主要挑战之一，事实证明，疫苗和治疗方法在控制其传播方面存在困难。普拉梭菌（F.prausnitzii）是肠道中的一种关键共生细菌，因其具有广泛的潜在健康益处，已被公认为下一代益生菌的有前途的候选者。普拉梭菌丰度的降低与某些病毒感染有关，这表明其在预防肠道病毒感染方面具有潜在应用价值。在本研究中，我们利用仔猪模型来研究普拉梭菌在PEDV感染中的潜在作用。
建立了PEDV感染的仔猪模型并补充了普拉梭菌，结果显示普拉梭菌减轻了PEDV感染。进一步研究发现，外膜囊泡（OMVs）是普拉梭菌的主要功能成分，并使用蛋白质组学、非靶向代谢组学和小RNA测序来分析OMVs的组成。肠道微生物群耗尽表明，Fp.OMVs的功能依赖于肠道微生物群的存在。此外，宏基因组分析表明，Fp.OMVs改变了肠道微生物群组成，增加了普拉梭菌、蒂莫内普雷沃氏菌和罗伊氏乳杆菌的丰度。非靶向代谢组学分析表明，Fp.OMVs增加了磷脂酰胆碱（PC）水平，PC被确定为减轻PEDV感染的关键代谢物。单细胞测序显示，PC改变了肠道细胞的相对丰度，增加了肠道上皮细胞的数量，并减少了靶细胞中的坏死性凋亡。在感染的IPEC-J2和Vero细胞中进行PC处理可减轻坏死性凋亡，并降低RIPK1-RIPK3-MLKL信号轴的激活，从而改善PEDV感染。
普拉梭菌及其OMVs在减轻PEDV感染中起关键作用。这些发现为改善仔猪PEDV感染提供了一种有前途的策略。视频摘要。
