Abstract

Introduction: Gut microbiota (GMB) has been associated with obesity in children, but no studies have examined GMB with direct measures of fat mass and trunk fat in children. In our study we examine GMB and GMB metabolites with overall body fat and trunk fat mass (TFM) measured by dual x-ray absorptiometry (DXA) in 5-year-old children. Hypothesis: GMB composition and GMB metabolites are associated with DXA-measured overall fat and TFM. Methods: We conducted our study in children from the Gen3G cohort, a community-based cohort enrolled prenatally in 2010-2013 in Quebec, Canada. A total of 153 children had data on GMB and 140 had data on plasma metabolites in addition to DXA scan at 5-6.5 years of age. We assessed GMB by 16s rRNA sequencing of stool samples, and measured plasma metabolites using the untargeted approach by Metabolon. We used multivariable-adjusted (see figure for covariates) linear regression to examine associations of DXA measured fat with 67 pre-defined GMB-derived metabolites from the Metabolon database. We used ANCOM-BC to examine 542 GMB amplicon sequence variants (ASVs) with body composition measurements. We used a false discovery rate (FDR) correction for multiple testing and considered an FDR value of < 0.2 as significant. Results: Of the 153 children, 43.1% female, 96.1% self-identified as white. Average BMI z-score was 0.18 ± 0.90, with average TFM 2125 ± 637 g. A total of 7 ASVs were associated with total body fat, 3 ASVs with TFM, and 1 ASV with BMI ( Fig. panel A ). Of 67 metabolites tested, 1 was associated with total body fat, 2 with TFM, and 3 with BMI. The two metabolites associated with TFM in a linear fashion ( Fig. panel B ) were deoxycholic acid and glycoursodeoxycholate, which are know to be involved in secondary bile acid metabolism and the etiology of diabetes. Conclusion: In children, associations of GMB composition and metabolites with DXA-measured overall fat mass, TFM, and BMI were in a similar direction. In particular, GMB metabolites related to bile acid metabolism were related to adipose tissue accumulation.

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