The Microbial Metabolite Indole-3-acetic Acid Alleviates Rumen Epithelial Barrier Integrity by Modulating AhR Activation in Dairy Cows With Ketosis

Ketosis is the most prevalent postpartum metabolic disorder in high-yielding dairy cows during early lactation and is often accompanied by rumen microbiota dysbiosis and systemic inflammation. However, the mechanisms by which microbial changes affect the integrity of the rumen epithelial barrier need to be elucidated. This study integrated 16S rRNA gene sequencing with untargeted metabolomics to assess host-ruminal microbiota interactions in ketotic dairy cows. Our findings revealed that ketosis-induced microbial perturbations were associated with an increase in lipopolysaccharide (LPS) levels, disrupted tryptophan metabolism, and a substantial reduction in indole-3-acetic acid (IAA), an important microbial metabolite. The depletion of probiotic genera, including Lactobacillus and Bifidobacterium, along with the enrichment of proinflammatory taxa, including Candidatus Saccharimonas and Mycoplasma, contributed to epithelial inflammation and disruption of barrier function. IAA supplementation in vitro activated the aryl hydrocarbon receptor (AhR)/IL-22 pathway to alleviate LPS-mediated damage to bovine rumen epithelial cells (BRECs), thereby accelerating epithelial regeneration while improving barrier function. Our findings revealed a new mechanism linking rumen microbiota-derived tryptophan metabolites to epithelial barrier integrity and suggested that targeting the microbiota-tryptophan AhR/IL-22 axis may offer new strategies for improving the health of the rumen in ketotic cows.