Background: Obesity is an established risk factor for multiple cancer types. Lower microbial richness has been linked to obesity, but human studies are inconsistent, and associations of early-life body mass index (BMI) with the fecal microbiome and metabolome are unknown.

Methods: We characterized the fecal microbiome (n = 563) and metabolome (n = 340) in the Northern Finland Birth Cohort 1966 using 16S rRNA gene sequencing and untargeted metabolomics. We estimated associations of adult BMI and BMI history with microbial features and metabolites using linear regression and Spearman correlations (rs) and computed correlations between bacterial sequence variants and metabolites overall and by BMI category.

Results: Microbial richness, including the number of sequence variants (rs = −0.21, P < 0.0001), decreased with increasing adult BMI but was not independently associated with BMI history. Adult BMI was associated with 56 metabolites but no bacterial genera. Significant correlations were observed between microbes in 5 bacterial phyla, including 18 bacterial genera, and metabolites in 49 of the 62 metabolic pathways evaluated. The genera with the strongest correlations with relative metabolite levels (positively and negatively) were Blautia, Oscillospira, and Ruminococcus in the Firmicutes phylum, but associations varied by adult BMI category.

Conclusions: BMI is strongly related to fecal metabolite levels, and numerous associations between fecal microbial features and metabolite levels underscore the dynamic role of the gut microbiota in metabolism.

Impact: Characterizing the associations between the fecal microbiome, the fecal metabolome, and BMI, both recent and early-life exposures, provides critical background information for future research on cancer prevention and etiology.