Associations of adiposity with gut microbiota composition among adults – results from a federated analysis of individual participant data from eight European observational studies

Gut microbiota may contribute to the adiposity-associated disease risk, but human studies reported inconsistent associations of adiposity with gut microbiota composition. We examined associations of body mass index (BMI) with alpha diversity and relative microbial abundance at the phylum and genus taxonomic levels (based on 16S rRNA amplicon sequencing or metagenomics) among 7,415 adults from eight European observational studies in a joint federated analysis of harmonized data using DataSHIELD. Higher BMI (per 5 kg/m2) was associated with lower alpha diversity (β: -0.05; 95%CI -0.07, -0.03), and on the phylum level positively associated with Proteobacteria, but neither with Firmicutes or Bacteroidetes nor their ratio, where high between-study heterogeneity was observed. On the genus level, BMI was inversely associated with the relative abundance of Faecalibacterium of the Firmicutes phylum (β: -0.11; 95%CI -0.14, -0.07), but positively with the odds of detection of Dorea, Streptococcus and Clostridium (all three Firmicutes) as well as Collinsella (Actinobacteria). This federated analysis of multiple studies found lower alpha diversity, alongside depleted Faecalibacterium, as well higher odds of detection of Dorea, Streptococcus, Clostridium and Collinsella with higher adiposity. By combining data from diverse study populations using harmonized data and statistical methods, our analysis partly overcomes sources of heterogeneity that may explain previously observed inconsistencies.