Pork and salmon diets differentially modulate lipid oxidation along the gastrointestinal tract in rats, with limited effects on gut microbiota.

Red meat consumption has been associated with less favorable health outcomes, whereas fish intake is often considered beneficial. These differences may partly relate to variations in fatty acid composition and heme iron content, which can influence oxidative processes during digestion and thereby affect intestinal and systemic responses. This study investigated the effects of pork- and salmon-based diets, differing primarily in fatty acid profile and heme iron content but matched for macronutrient composition, on oxidative stress, gut microbiota, fermentation metabolites, and inflammation in rats. The pork-based diet supplied 2.3-fold more SFA and 14-fold more heme iron than the salmon-based diet, which in turn provided 14-fold more n-3 PUFA. Consumption of pork significantly increased propanal (+81%), hexanal (17-fold), and 4-hydroxy-2-nonenal (27-fold) in stomach contents, and elevated thiobarbituric acid reactive substances (TBARS, +45%) in plasma. In contrast, salmon consumption raised TBARS in duodenal mucosa (+19%) and C-reactive protein (+30%) in plasma. Only subtle diet-related changes were observed in gut microbiota composition and fermentation metabolites, with no difference in fecal calprotectin. A small number of discriminant taxa were identified, including Clostridioides and Muribaculum in salmon-fed rats and Eubacterium fissicatena, Sellimonas, and Dielma in pork-fed rats, while valerate levels were higher in pork-fed rats. Transcriptomic analysis revealed that no individual genes remained significant after correction for multiple testing. Overall, pork and salmon diets differentially modulated lipid oxidation along the gastrointestinal tract, whereas their effects on gut microbiota were limited.