Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbiosis. However, it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets. In this study, we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score, and elevated levels of lipopolysaccharide (LPS) and D-lactate (D-LA) compared to healthy piglets. Subsequently, we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets. Diarrheal piglets demonstrated intestinal microbiota dysbiosis, characterized primarily by a higher Firmicutes to Bacteroidota ratio, a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri, and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron. Functional profiling of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data was performed, and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diarrhea. Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets. Furthermore, we explored the effects of dietary indole-3-aldehyde (IAld), a key tryptophan metabolite, on intestinal development and gut barrier function in weaned piglets. Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell (ISC) expansion in piglets. The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids. These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intestinal development by promoting ISC expansion in weaned piglets.

中文翻译：

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肠道微生物代谢物吲哚-3-醛通过促进断奶仔猪肠道干细胞扩增来缓解肠道发育受损


撤机应激引起的腹泻被广泛认为与肠道微生物群失调有关。然而，要阐明哪些特定的肠道微生物群及其代谢物在断奶仔猪的止泻过程中起关键作用一直具有挑战性。在这项研究中，我们首先观察到，与健康仔猪相比，腹泻仔猪的平均日增重较低，腹泻评分较高，脂多糖 （LPS） 和 D-乳酸 （D-LA） 水平较高。随后，我们分析了健康断奶仔猪和腹泻断奶仔猪之间肠道微生物组成和代谢物水平的差异。腹泻仔猪表现出肠道菌群失调，主要特征是厚壁菌门与拟杆菌门比率较高，淀粉乳杆菌和罗伊氏乳杆菌缺乏，以及拟杆菌属丰度增加。HF-5287 和 Bacteroides thetaiotaomicron。根据京都基因与基因组百科全书 （KEGG） 数据对肠道菌群进行功能分析，结果显示色氨酸代谢是腹泻仔猪中抑制最显着的途径。在腹泻仔猪中检测到的大多数色氨酸代谢物的浓度低于健康仔猪。此外，我们探讨了日粮中吲哚-3-醛 （IAld） 对断奶仔猪肠道发育和肠道屏障功能的影响。在日粮中添加 100 mg/kg IAld 通过促进仔猪肠道干细胞 （ISC） 扩增来提高小肠指数并改善肠道屏障功能。IAld 对 ISC 扩增的促进也在猪肠道类器官中得到证实。 这些发现表明，肠道微生物色氨酸代谢物 IAld 通过促进断奶仔猪的 ISC 扩增来减轻肠道发育受损。