A genomic atlas of gut clostridia: phylogeny, butyrate, and propionate production

Introduction Clostridia is a major microbial class in the human gut, crucial for fermenting undigested carbohydrates and proteins, which produce short-chain fatty acids essential for gut health and immune balance. This study revised the taxonomic classification and phylogeny of all the species of intestinal Clostridia catalogued in the Unified Human Gastrointestinal Genome database using a whole-genome approach and assessed butyrate and propionate producing species.Methods A total of 1,897 Clostridia species, including those with recognised binomial nomenclature and those lacking formal taxonomic classification, were retrieved and reclassified using GTDB-Tk. Their phylogeny was determined by identifying, concatenating, and aligning the 120 ubiquitous single-copy proteins defined in the GTDB. Average amino acid identity (AAI), percentage of conserved proteins (POCP), and phylogenetic relationships were used to organize the species into genera and families. The presence of enzymes belonging to the biosynthetic pathways for butyrate and propionate production was investigated in all genomes with the tool GapSeq.Results Reclassification of the genomes resulted in 404 recognised species and 1,493 species lacking formal taxonomic classification. Oscillospirales and Lachnospirales encompassed most of the species. The pathways leading to butyrate and propionate production were analyzed in their entirety, revealing 519 species as potential butyrate producers, 257 as potential propionate producers and 77 capable of producing both. To assess the abundance of each species, 151 faecal metagenomes of healthy subjects were profiled, indicating that butyrate producing Clostridia accounted on average for 28.0% of each microbiome.Conclusions This study offers a comprehensive overview of intestinal Clostridia diversity, emphasising their role in gut ecosystems and their potential for butyrate and propionate production.