The gut microbiome modulates the lipase-mediated digestion of dietary lipid emulsions

The gut microbiome plays a critical role in host lipid metabolism, yet its influence on the intraluminal processes governing dietary lipid digestion, particularly lipase-mediated hydrolysis at oil-water interfaces, remains poorly understood. In this study, we combined in vivo microbiome modulation in rats with an ex vivo lipolysis model to examine how microbial perturbations affect intestinal lipid digestion. Rats were pretreated for 14 days with either broad-spectrum antibiotics or a prebiotic to induce distinct microbial profiles. Small intestinal luminal contents were collected from the jejunum and used to monitor the ex vivo digestion of coconut oil and olive oil, representing dietary lipids with varying triglyceride chain lengths. Microbial diversity was positively associated with both the rate and extent of lipid digestion. Notably, the prebiotic group showed a 3-4-fold increase in fatty acid release compared to the antibiotic group after 60 min of digestion (p < 0.0001). Physicochemical analyses indicated that prebiotic treatment enhanced emulsification efficiency, increasing the interfacial surface area available for lipase adsorption by up to 250%. Biomolecular profiling revealed marked changes in the intestinal lipidome and proteome, together with changes in endogenous bile acid and carbohydrate concentrations suggesting that microbial modulation of the luminal milieu plays a critical role in lipid emulsification and bioaccessibility. Together, these findings demonstrate that microbiome composition directly impacts the physicochemical environment of the small intestine and shapes lipid digestion outcomes, highlighting the potential of microbiome-targeted strategies to enhance digestive efficiency and metabolic health.