Abstract

Objective: Dietary stearic acid (18:0), a major saturated fatty acid (SFA) in Western diets, does not raise plasma LDL-C concentrations relative to other shorter chain SFAs (palmitic [16:0], myristic [14:0] and lauric [12:0]), and is associated with lower CVD risk. We investigated whether the cardioprotective effects of 18:0 and its metabolic product oleic acid (18:1, a monounsaturated fatty acid) relative to 16:0 is mediated via alterations in the gut microbiome. Methods: Twenty mildly hypercholesterolemic (LDL-C>100mg/dL) post-menopausal women (50-85 years; BMI 25-35kg/m 2 ) consumed each of 3 isocaloric diets for 5 weeks according to a randomized controlled cross-over design. Diets provided 55%E carbohydrate, 15%E protein and 30%E fat with half of the fat provided by 16:0, 18:0 or 18:1, respectively. Fecal samples were collected at the end of each diet phase and shotgun metagenomic sequencing was performed. Alpha diversity (Shannon index, Simpson index and observed counts) was compared between diet groups using two-sample non-parametric tests. Beta-diversity was assessed using Bray-Curtis dissimilarity with PERMANOVA test. Differences in metagenomic features by diet group were evaluated using Partial Least Squares-Discriminant Analysis (PLS-DA) models of pairwise diet differences developed using the R package ‘mixOmics’. Results: No significant differences were observed in alpha and beta diversity between diet groups. However, the variability in microbial relative abundance was greater after participants consumed the 18:0 and 18:1 diets compared to the 16:0 diet. Specifically, mean relative abundance of Bacterioides dorei , Bacteroides vulgatus , and Ruminococcus were highest after participants consumed the 18:0 relative to the 16:0 diet and intermediate after the 18:1 diet. The relative abundance of Coprococcus , Parabacteroides distasonis , Coprobacillus and Blautia were higher after participants consumed the 18:1 relative to the 16:0 diet. These microbial species have been associated with several anti-inflammatory pathways and decreased bacterial lipopolysaccharide production. Conclusion: These data document modest but distinctive effects of dietary SFAs on gut microbiome composition and functionality, suggesting that the favorable effects of 18:0 and 18:1 relative to 16:0 on CVD risk factors could be mediated, in part, by the gut microbiome.

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