Abstract P495: Gut Microbiome and Plasma Metabolome Signatures Are Associated with Systemic Inflammation in Children

Introduction: Gut microbiota and microbial metabolites are hypothesized to influence health via systemic inflammation, but pediatric studies are lacking. We investigated associations of gut microbiota and plasma metabolome with inflammation in children aged 5-7. Hypothesis: Children with greater abundances of pro-inflammatory microbial taxa and metabolites have more systemic inflammation. Methods: We analyzed cross-sectional data from the community-based Gen3G cohort (Quebec), including children with 3 inflammation measures (IMs; plasminogen activator inhibitor 1, monocyte chemoattractant protein 1, tumor necrosis factor α), untargeted plasma metabolome (Metabolon platform) and gut microbiota (stool 16S rRNA sequencing) data at the 5-year visit. We log-transformed and standardized each IM, averaging them as an inflammation score (InfSc). We pareto-scaled log-transformed metabolites, imputing missing values as half the minimum detected. We selected 76 known bacterial metabolites a priori . We excluded metabolites detected in <50% of samples and microbial amplicon sequence variants (ASVs) in <10% of the samples or with <0.1% overall proportion. We examined associations of ASVs and metabolites with IMs and InfSc using ANCOM-BC2 and linear regression, respectively, after multivariable adjustment (see Figure legend). FDR p-values <0.05 were considered significant. Results: A total of 320 children (mean age 63±4 months, 47% female, 95% white) had IMs and metabolome data, and 146 had microbiota data. Of 335 ASVs tested, 59 were associated with InfSc and 154 with any IM (10 strongest associations in Figure A ). Of the 1038 total metabolites and 76 bacterial metabolites tested, 53 and 5 metabolites, respectively, were associated with InfSc and 80 and 10, respectively, with any IM (10 bacterial metabolites in Figure B ). Conclusions: Microbial ASVs and metabolites, including pro-inflammatory ones (e.g., P. succinatutens, lactate, kynurenine), were associated with systemic inflammation in 5yo children.