Microbiota-derived indole-3-acetic acid alleviates rumen epithelial barrier dysfunction during the peripartum period...

Peripartum dairy cows are highly susceptible to metabolic disorders, with ketosis being the most prevalent postpartum disease associated with rumen microbial dysbiosis and systemic inflammation. However, the mechanisms by which microbial alterations compromise rumen epithelial integrity remain poorly understood. Using peripartum cows with ketosis as a model, we demonstrated that perturbations of rumen microbiota disrupt tryptophan metabolism, resulting in pronounced depletion of indole-3-acetic acid (IAA). The loss of IAA-producing taxa (Lactobacillus and Bifidobacterium) contributed to reduced IAA levels and epithelial barrier dysfunction, whereas enrichment of proinflammatory taxa (Candidatus Saccharimonas and Mycoplasma) was associated with exacerbated epithelial inflammation. In vitro, IAA supplementation activated the AhR/IL-22 signaling pathway, promoting bovine rumen epithelial cells (BRECs) regeneration and restoring barrier integrity. These findings identify the microbiota-IAA-AhR/IL-22 axis as a key regulator of rumen epithelial homeostasis and suggest that targeting this pathway represents a promising strategy to prevent metabolic disorders in dairy cows.