Caffeic acid modulates intestinal microbiota, alleviates inflammatory response, and enhances barrier function in a piglet model challenged with lipopolysaccharide

Young animals are highly susceptible to intestinal damage due to incomplete intestinal development, making them vulnerable to external stimuli. Weaning stress in piglets, for instance, disrupts the balance of intestinal microbiota and metabolism, triggering intestinal inflammation and resulting in gut damage. Caffeic acid (CA), a plant polyphenol, can potentially improve intestinal health. Here, we evaluated the effects of dietary CA on the intestinal barrier and microbiota using a lipopolysaccharide (LPS)-induced intestinal damage model. Eighteen piglets were divided into three groups: control group (CON), LPS group (LPS), and CA + LPS group (CAL). On the 21st and 28th day, six piglets in each group were administered either LPS (80 mu g/kg body weight; Escherichia coli O55:B5) or saline. The results showed that dietary CA improved the intestinal morphology and barrier function, and alleviated the inflammatory response. Moreover, dietary CA also improved the diversity and composition of the intestinal microbiota by increasing Lactobacillus and Terrisporobacter while reducing Romboutsia. Furthermore, the LPS challenge resulted in a decreased abundance of 14 different bile acids and acetate, which were restored to normal levels by dietary CA. Lastly, correlation analysis further revealed the potential relationship between intestinal microbiota, metabolites, and barrier function. These findings suggest that dietary CA could enhance intestinal barrier function and positively influence intestinal microbiota and its metabolites to mitigate intestinal damage in piglets. Consuming foods rich in CA may effectively reduce the incidence of intestinal diseases and promote intestinal health in piglets. Our study demonstrates that dietary caffeic acid (CA) supplementation can alleviate intestinal inflammation and improve gut barrier function. It addresses the vulnerability to severe intestinal damage in piglets due to immature intestinal systems, potentially reducing economic losses for the pig industry. Additionally, CA shows potential in enhancing intestinal barrier function by regulating intestinal microbiota and metabolites, offering a new health-promoting solution for swine husbandry. Our study focuses on a major issue affecting young animals. After weaning, piglets are particularly vulnerable to severe intestinal infections due to their immature intestinal systems, leading to damaged barriers and financial losses for the pig industry. We explore the possibility of using caffeic acid (CA), a natural compound found in plants, to promote intestinal health. Our research shows that adding CA to the diet can reduce intestinal inflammation and improve barrier function in weaned piglets challenged by lipopolysaccharide. CA positively affects ileal microbiota by increasing beneficial bacteria like Lactobacillus and Terrisporobacter and decreasing Romboutsia. We also observed differing regulatory effects of CA between the ileum and colon, with opposite changes in primary bile acids. Our findings emphasize the potential of CA as a dietary supplement to improve intestinal barrier function and modulate the inflammatory response by targeting gut microbiota and metabolites. To our knowledge, this is the first to demonstrate the effects of CA on ileal barrier function and microbiota in piglets. Our findings could significantly benefit the pig industry by mitigating financial losses from serious intestinal infections. Additionally, this research may offer key insights into the health of human infants' intestines. Graphical Abstract