A unified catalog of 204,938 reference genomes from the human gut microbiome

TLDR

Comprehensive, high‑quality reference genomes are essential for functional characterization and taxonomic assignment of the human gut microbiota. The authors present the Unified Human Gastrointestinal Genome (UHGG) collection, comprising 204,938 nonredundant genomes from 4,644 gut prokaryotes. They collated over 170 million protein sequences from these genomes into the Unified Human Gastrointestinal Protein (UHGP) catalog. The UHGP more than doubles the gut protein repertoire relative to the Integrated Gene Catalog, yet 40 % of its proteins lack functional annotations, 70 % of UHGG species are uncultured, and intraspecies variation reveals population‑specific accessory genes and single‑nucleotide variants, making the UHGG/UHGP collections comprehensive resources for linking gut microbiome genotypes to phenotypes.

Abstract

Comprehensive, high-quality reference genomes are required for functional characterization and taxonomic assignment of the human gut microbiota. We present the Unified Human Gastrointestinal Genome (UHGG) collection, comprising 204,938 nonredundant genomes from 4,644 gut prokaryotes. These genomes encode >170 million protein sequences, which we collated in the Unified Human Gastrointestinal Protein (UHGP) catalog. The UHGP more than doubles the number of gut proteins in comparison to those present in the Integrated Gene Catalog. More than 70% of the UHGG species lack cultured representatives, and 40% of the UHGP lack functional annotations. Intraspecies genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which are specific to individual human populations. The UHGG and UHGP collections will enable studies linking genotypes to phenotypes in the human gut microbiome. More than 200,000 gut prokaryotic reference genomes and the proteins they encode are collated, providing comprehensive resources for microbiome researchers.