| Summary: | The role of volatile fatty acids (VFAs) in ruminal fermentation is well studied, but their effects on the ileal microbiome and epithelial health remain less explored. In this study, we investigated the impact of the exogenous oral infusion of three VFAs, sodium acetate (NaAc), propionate (NaPr), and butyrate (NaBu), on the VFA concentrations in ileal contents, as well as ileal microbiome profiling and epithelial health parameters (inflammatory cytokine and tight junctions) in goats. The data demonstrated that the oral infusion of three VFAs can enhance VFA production by increasing the proportions of each individual VFA and the total VFAs. Then, the microbiome revealed distinct microbial succession patterns and altered microbial diversities in response to the oral infusion of VFA treatments. Moreover, the oral infusion of each VFA had unique effects on the ileal bacterial community, with potential implications for epithelial health. Notably, the oral infusion of VFAs demonstrated potential anti-inflammatory effects, as evidenced by reduced IL-6 levels in the NaPr group and increased IL-10 levels in the NaAc group. Notably, the oral infusion of VFAs did not directly impact the tight junction concentrations, such as Claudin1, Occludin, and ZO-1. Lastly, the correlation analyses identified specific relationships between the ileal bacteria and epithelial health parameters, and <i>Prevotella</i> was positively correlated with IL-6 and IL-1β, while <i>Bifidobacterium</i> was positively correlated with IL-10. These results highlighted the crosstalk between VFAs, the ileal microbiome, and the health of the small intestine. Our findings had significant implications for optimizing ruminant nutrition, enhancing epithelial health, and promoting sustainable livestock production practices.
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