Synbiotics regulate gut microbiota-derived indole-3-acetic acid production to modulate the intestinal barrier and improve antibiotic-associated diarrhea

作者：Yi Shan, Miaomiao Zheng, Yu Zhao, Shanshan Sha, Chun Bian · 发表于：Journal of Dairy Science · 年份：2026 · DOI：10.3168/jds.2025-28138 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research、Probiotics and Fermented Foods

Given the global risks associated with antibiotic overuse, antibiotic-associated diarrhea (AAD) has become a widespread public health concern worldwide. Human milk oligosaccharides (HMO) and bifidobacteria are often used to prepare synbiotics to enhance their health effects. However, the synergistic effect of this combination in alleviating AAD remains unclear. In this study, lincomycin was used to establish a mouse model of AAD, and the effects of 3-fucosyllactose with 6'-sialyllactose, as well as Bifidobacterium bifidum, were evaluated. Further analyses examined the effects of HMO plus probiotics on the gut microbiota and its associated metabolites. In addition, the roles and underlying mechanisms of specific metabolites in AAD were investigated. The results indicate that HMO plus probiotics significantly ameliorate diarrheal symptoms in mice with AAD. This effect is reflected by increased body weight, markedly reduced diarrhea scores and fecal water content, significantly elevated aquaporin-3 (AQP3) expression, and substantially decreased levels of the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, the combination of HMO and probiotics demonstrated superior efficacy compared with either intervention alone. Integrated microbiome-metabolomics analysis revealed that HMO plus probiotics significantly enriched Lactobacillus, a change that was potentially associated with increased levels of the gut metabolite indole-3-acetic acid (IA...