Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p 0. 05), with a significant increase in norankfMuribaculaceae and PrevotellaceaeNK3B31group colonization compared with lincomycin group (p < 0. 05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norankMuribaculaceae and Akkermansia (p < 0. 05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.