Colonic Fermentation and Acetate Production in Youth with and without Obesity

BACKGROUND: In the last few years, there has been a growing interest in the role of gut microbiota in the development of obesity and its complications. OBJECTIVES: In this study, we tested the following hypotheses: 1) lean youth and youth with obesity experience a different capability of their gut microbiota to ferment carbohydrates and produce acetate; and 2) colonic acetate may serve as a substrate for hepatic de novo lipogenesis (DNL). METHODS: Nineteen lean youth [mean ± SE BMI (in kg/m(2)): 21.8 ± 0.521] and 19 youth with obesity (BMI: 35.7 ± 1.66), ages 15–21 y, frequency-matched by age and sex, underwent a fasting 10-h sodium [d(3)]-acetate intravenous infusion to determine the rate of appearance of acetate (Ra(acet)) into the peripheral circulation before and after an oral dose of 20 g of lactulose. Pre- and post-lactulose Ra(acet) values were determined at a quasi-steady state and changes between groups were compared using a quantile regression model. Acetate-derived hepatic DNL was measured in 11 subjects (6 youth with obesity) and its association with Ra(acet) was assessed using Spearman correlation. RESULTS: Mean ± SE Ra(acet) was not different before lactulose ingestion between the 2 groups (7.69 ± 1.02 μmol · kg(−1) · min(−1) in lean youth and 7.40 ± 1.73 μmol · kg(−1) · min(−1) in youth with obesity, P = 0.343). The increase in mean ± SE Ra(acet) after lactulose ingestion was greater in lean youth than in youth with obesity (14.7 ± 2.33 μmol · kg(−1) · min(−1) and 9.29 ± 1.44 μmol · kg(−1) · min(−1), respectively, P = 0.001). DNL correlated with Ra(acet), calculated as changes from the pre- to the post-lactulose steady state (ρ = 0.621; P = 0.046). CONCLUSIONS: These data suggest that youth with obesity ferment lactulose to a lesser degree than youth without obesity and that colonic acetate serves as a substrate for hepatic DNL. This trial was registered at clinicaltrials.gov as NCT03454828.