Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population

Cell Rep. 2023 Nov 28;42(11):113324. doi: 10.1016/j.celrep.2023.113324. Epub 2023 Nov 6.


Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population.

Keywords: ABO blood types; CP: Genomics; GWAS; gut microbiome; human genome; plasma metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Group Antigens*
  • East Asian People
  • Gastrointestinal Microbiome* / genetics
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics
  • Humans
  • Metabolome
  • Repressor Proteins / genetics


  • Blood Group Antigens
  • TGIF2 protein, human
  • Repressor Proteins
  • Homeodomain Proteins