Abstract

Introduction: The short-chain fatty acids (SCFA) acetic acid, propionic acid, and butyric acid are microbial-produced metabolites that can influence host physiology through regulation of hepatic cholesterol metabolism. These biologically relevant gut metabolites may play a role in the hypocholesterolemic effects of select dietary components. The objective of this exploratory study was to determine the effects of diets that differ only in fatty acid composition on fecal SCFA levels and to assess their correlations with circulating lipids, lipoproteins, and apolipoproteins. Hypothesis: We assessed the hypothesis that dietary fat quality will differentially affect fecal SCFA and there will be significant associations between fecal SCFA levels and those of circulating total cholesterol, low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and apolipoprotein (apo) B. Methods: In a double-blind, randomized, three period crossover, controlled feeding clinical trial, participants with ≥2 metabolic syndrome criteria (n=20) were provided with a weight maintenance, controlled feeding base diet plus conventional canola oil, high-oleic acid canola oil (HOCO), or a control oil (control diet formulated to represent a Western diet fatty acid profile) for 6 weeks followed by washout periods of ≥4 weeks. The macronutrient profiles of the diets were: canola diet [17.5% monounsaturated fatty acid (MUFA), 9.2% polyunsaturated fatty acid (PUFA), 6.6% saturated fatty acid (SFA)], HOCO diet (19.1% MUFA, 7.0% PUFA, 6.4% SFA), and control diet (10.5% MUFA, 10.0% PUFA, 12.3% SFA). Fecal and blood samples were collected at study enrollment and at the end of each diet. Results: After 6 weeks, a trend toward a treatment effect on endpoint fecal propionic acid was observed ( P =0.09), with a trend toward a higher concentration following the control compared to the canola diet ( P =0.09). Acetic acid was increased from baseline following the control diet ( P =0.04). After the control diet only, fecal levels of propionic acid were positively correlated with blood levels of LDL-C, non-HDL-C, and apo B (r=0.52 to 0.64, P =0.003 to 0.02), with a trend for total cholesterol (r=0.39, P =0.10), and acetic acid was positively correlated with LDL-C and apo B levels (r=0.48 to 0.49, P =0.03 to 0.04), with a trend for non-HDL-C (r=0.44, P =0.06). No significant correlations between fecal SCFA and lipids and lipoproteins were observed after the two canola oil-based diets. Conclusions: In conclusion, these data suggest that the adverse effects of a contemporary Western diet fatty acid profile on circulating lipid and lipoprotein parameters compared to diets higher in unsaturated fat and lower in SFA may be mediated by gut-derived SCFA.

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