Host-gene signals point to gut physiology as main driver of microbiome diversity
A large GWAS of harmonized gut metagenomic data from 16,017 Swedish adults with replication in 12,652 Norwegians identifies host genetic variants linked to microbiome richness and 149 species; the strongest signal at OR51E1–OR51E2 suggests enteroendocrine fatty acid sensing shapes microbial communities, with additional loci near mucin genes and bile-acid pathways. Mendelian randomization links some taxa to LDL cholesterol and BMI-related traits, underscoring gastrointestinal physiology as a key driver of microbiome variation. Limitations include European-ancestry focus and challenges in pinpointing causal genes.