Butyrate-producing bacteria have recently gained attention, since they are important for a healthy colon and when altered contribute to emerging diseases, such as
ulcerative colitis and type II diabetes. This guild is polyphyletic and cannot be accurately detected by
16S rRNA gene sequencing. Consequently, approaches targeting the terminal genes of the main
butyrate-producing pathway have been developed. However, since additional pathways exist and alternative, newly recognized
enzymes catalyzing the terminal reaction have been described, previous investigations are often incomplete. We undertook a broad analysis of
butyrate-producing pathways and individual genes by screening 3,184 sequenced bacterial genomes from the Integrated Microbial Genome database. Genomes of 225 bacteria with a potential to produce
butyrate were identified, including many previously unknown candidates. The majority of candidates belong to distinct families within the Firmicutes, but members of nine other phyla, especially from Actinobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Thermotogae, were also identified as potential
butyrate producers. The established gene catalogue (3,055 entries) was used to screen for
butyrate synthesis pathways in 15 metagenomes derived from stool samples of healthy individuals provided by the HMP (Human Microbiome Project) consortium. A high percentage of total genomes exhibited a
butyrate-producing pathway (mean, 19.1%; range, 3.2% to 39.4%), where the
acetyl-coenzyme A (
CoA) pathway was the most prevalent (mean, 79.7% of all pathways), followed by the
lysine pathway (mean, 11.2%). Diversity analysis for the
acetyl-CoA pathway showed that the same few firmicute groups associated with several Lachnospiraceae and Ruminococcaceae were dominating in most individuals, whereas the other pathways were associated primarily with Bacteroidetes. IMPORTANCE Microbiome research has revealed new, important roles of our gut microbiota for maintaining health, but an understanding of effects of specific microbial functions on the host is in its infancy, partly because in-depth functional microbial analyses are rare and publicly available databases are often incomplete/misannotated. In this study, we focused on production of
butyrate, the main energy source for colonocytes, which plays a critical role in health and disease. We have provided a complete database of genes from major known
butyrate-producing pathways, using in-depth genomic analysis of publicly available genomes, filling an important gap to accurately assess the
butyrate-producing potential of complex microbial communities from "-omics"-derived data. Furthermore, a reference data set containing the abundance and diversity of
butyrate synthesis pathways from the healthy gut microbiota was established through a metagenomics-based assessment. This study will help in understanding the role of
butyrate producers in health and disease and may assist the development of treatments for functional
dysbiosis.