Dietary isochlorogenic acid ameliorates intestinal inflammation and barrier damage by modulating gut microbiota and promoting L-lysine metabolism in LPS-challenged broilers

Abstract As a plant extract, isochlorogenic acid (ICA) has attracted increasing attention due to its functions in regulating intestinal health, immunity and anti-inflammatory responses. This study utilized lipopolysaccharide (LPS) to induce intestinal injury in broilers, aiming to explore the role of intestinal microbes and their metabolites in alleviating immune stress and maintaining intestinal barrier function after dietary ICA supplementation. The experiments demonstrated that under normal growth conditions, ICA significantly enhanced the average daily gain and final weight of broilers while markedly reducing the feed-to-weight ratio. Under LPS challenge, compared with the LPS treatment group, the addition of ICA to the diet significantly decreased the pH value of the ileum, markedly increased digestive enzyme activity, and elevated the content of volatile fatty acids in the chyme. Moreover, a notable rise was observed in the abundance of Streptococcus _ alactolyticus , along with notable enrichment of metabolites such as L-Lysine. Changes in the gut microbiota and metabolites facilitate improvements in ileal structure, including a significant increase in villus height, mitigation of cellular vacuolization and marked upregulation of the mRNA expression of the tight junction protein Claudin-1. Simultaneously, the function of the intestinal immune barrier was strengthened, which mitigated the rise in inflammatory factor levels and the upregulation of mRNA expression in relevant signaling pathways triggered by LPS. The correlation analysis further reveals the potential associations between metabolites and specific intestinal microbiota and the relationships between metabolites and indicators reflecting intestinal barrier function, such as intestinal structure, gene expression and inflammation markers. These results indicate that ICA enhances gut barrier function and mitigates intestinal inflammation to some extent by modulating the composition of intestinal microbiota and metabolites.