Integrating Serum Metabolome and Gut Microbiome to Evaluate the Benefits of Lauric Acid on Lipopolysaccharide- Challenged Broilers.

Lauric acid (LA) is a crucial medium-chain fatty acid (MCFA) that has many beneficial effects on humans and animals. This study aimed to investigate the effects of LA on the intestinal barrier, immune functions, serum metabolism, and gut microbiota of broilers under lipopolysaccharide (LPS) challenge. A total of 384 one-day-old broilers were randomly divided into four groups, and fed with a basal diet, or a basal diet supplemented with 75 mg/kg antibiotic (ANT), or a basal diet supplemented with 1000 mg/kg LA. After 42 days of feeding, three groups were intraperitoneally injected with 0.5 mg/kg - derived LPS (LPS, ANT+LPS and LA+LPS groups) for three consecutive days, and the control (CON) group was injected with the same volume of saline. Then, the birds were sacrificed. Results showed that LA pretreatment significantly alleviated the weight loss and intestinal mucosal injuries caused by LPS challenge. LA enhanced immune functions and inhibited inflammatory responses by upregulating the concentrations of immunoglobulins (IgA, IgM, and IgY), decreasing IL-6 and increasing IL-4 and IL-10. Metabolomics analysis revealed a significant difference of serum metabolites by LA pretreatment. Twenty-seven serum metabolic biomarkers were identified and mostly belong to lipids. LA also markedly modulated the pathway for sphingolipid metabolism, suggesting its ability to regulate lipid metabolism. Moreover,16S rRNA analysis showed that LA inhibited LPS-induced gut dysbiosis by altering cecal microbial composition (reducing , and , and increasing and ), and modulating the production of volatile fatty acids (VFAs). Pearson's correlation assays showed that alterations in serum metabolism and gut microbiota were strongly correlated to the immune factors; there were also strong correlations between serum metabolites and microbiota composition. The results highlight the potential of LA as a dietary supplement to combat bacterial LPS challenge in animal production and to promote food safety.