Obese Mice Losing Weight Due to trans-10, cis-12 Conjugated Linoleic Acid Supplementation or Food Restriction Harbor Distinct Gut Microbiota

Background: trans-10, cis-12 Conjugated linoleic acid (t10, c12-CLA) is a dietary supplement that promotes weight loss by increasing fat oxidation and energy expenditure. We previously reported that in the absence of t10, c12-CLA, mice forced to lose equivalent body weight by food restriction (FR) do not exhibit increases in fat oxidation or energy expenditure but have improved glucose metabolism, consistent with FR as a metabolically healthy weight-loss method. Objective: Because diet is a primary determinant of gut bacterial populations, we hypothesized that the disparate metabolic effects accompanying weight loss from t10, c12-CLA or FR could be related to altered intestinal microbiota. Methods: Ten-week-old male LDL receptor-deficient (Ldlr(-/-)) mice were fed a high-fat, high-sucrose diet (HFHS; 36% lard fat, 36.2% sucrose + 0.15% cholesterol) for 12 wk (baseline), then switched to the HFHS diet alone (obese control), HFHS + 1% c9, t11-CLA (obese fatty acid control), HFHS + 1% t10, c12-CLA (weight-loss-inducing fatty acid), or HFHS + FR (weight-loss control group with 75-85% ad libitum HFHS food intake) for a further 8 wk. Fecal microbial content, short-chain fatty acids (butyrate, acetate), tissue CLA concentrations, and intestinal nutrient transporter expression were quantified. Results: Mice fed t10, c12-CLA or assigned to FR lost 14.5% of baseline bodyweight. t10, c12-CLA-fed mice had elevated concentrations of fecal butyrate (2-fold) and plasma acetate (1.5-fold) compared with HFHS-fed controls. Fecal a diversity decreased by 7.6-14% in all groups. Butyrivibrio and Roseburia, butyrate-producing microbes, were enriched over time by t10, c12-CLA. By comparing with each control group, we also identified bacterial genera significantly enriched in the t10, c12-CLA recipients, including Lactobacillus, Actinobacteria, and the newly identified Ileibacterium valens of the Allobaculum genus, whereas other taxa were enriched by FR, including Clostridiales and Bacteroides. Conclusion: Modalities resulting in equivalent weight loss but with divergent metabolic effects are associated with compositional differences in the mouse intestinal microbiota.