Colonic Fermentation and Acetate Production in Youth with and without Obesity

Abstract

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/m2): 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 [d3]-acetate intravenous infusion to determine the rate of appearance of acetate (Raacet) into the peripheral circulation before and after an oral dose of 20 g of lactulose. Pre- and post-lactulose Raacet 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 Raacet was assessed using Spearman correlation.

Results: Mean ± SE Raacet 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 Raacet 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 Raacet, 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.

Keywords: acetate; childhood obesity; colonic fermentation; de novo lipogenesis; gut microbiota; isotope infusion study; obese youth; rate of appearance; short-chain fatty acids.