A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria

Abstract

Several bacterial families are known to be highly abundant within the human microbiome, but their ecological roles and evolutionary histories have yet to be investigated in depth. One such family, Lachnospiraceae (phylum Firmicutes, class Clostridia) is abundant in the digestive tracts of many mammals and relatively rare elsewhere. Members of this family have been linked to obesity and protection from colon cancer in humans, mainly due to the association of many species within the group with the production of butyric acid, a substance that is important for both microbial and host epithelial cell growth. We examined the genomes of 30 Lachnospiraceae isolates to better understand the origin of butyric acid capabilities and other ecological adaptations within this group. Butyric acid production-related genes were detected in fewer than half of the examined genomes with the distribution of this function likely arising in part from lateral gene transfer (LGT). An investigation of environment-specific functional signatures indicated that human gut-associated Lachnospiraceae possess genes for endospore formation, whereas other members of this family lack key sporulation-associated genes, an observation supported by analysis of metagenomes from the human gut, oral cavity, and bovine rumen. Our analysis demonstrates that adaptation to an ecological niche and acquisition of defining functional roles within a microbiome can arise through a combination of both habitat-specific gene loss and LGT.

Keywords: butyric acid; lateral gene transfer; metagenomics; microbial genomes; phylogenomics; sporulation.

Fig. 1.—

Environmental distribution of the Lachnospiraceae. A total of 25 16S rRNA gene surveys containing a total of 1,697 samples covering 17 different habitat classes were taxonomically profiled to identify the overall percentage of Lachnospiraceae. Boxplots outline the 25th, 50th, and 75th percentiles of the data. The minimum, maximum, and average (red box) percent abundance per sample of this family are also indicated. The number of samples per environment is listed beside habitat type and in supplementary table S1, Supplementary Material online. Each GI tract-associated habitat is highlighted in bold.

Fig. 2.—

Grouping of genomes based on counts of shared gene clusters. Heatmap shows the number of gene clusters shared between genomes, inversely weighted by genome size. Genomes are clustered with intersecting cells between two genomes colored based on similarity ranging from low (red) to high (blue). The hierarchy of clustering is displayed along the side and top of the heat map with branches colored according to habitat (yellow, oral; red, sediment; green, rumen; blue, human GI tract). Names of gut-associated members predicted to be lacking butyric acid production are highlighted by an asterisk.

Fig. 3.—

Distribution of sporulation-associated genes within Lachnospiraceae genomes. A range of sporulation genes was examined for each genome to assess the capabilities of producing endospores within each strain. Each gene is displayed as present (green) or absent (white) from each Lachnospiraceae genome. Organisms are clustered based on their distribution of sporulation genes. Hierarchical clustering of genomes is displayed at the top of the grid with branches colored according to habitat (yellow, oral; red, sediment; green, rumen; blue, human GI tract). Gray lines separate sporulation genes into the broad categories listed on the right-hand side.

Fig. 4.—

Relationships of 30 Lachnospiraceae genomes based on marker gene and concatenated alignments. Phylogenetic trees based on the 16S ribosomal RNA gene (A) and the family-wide shared orthologs (B). Trees are rooted using two Ruminococcaceae as outgroup. Branches are colored based on listed habitat (yellow, oral; red, sediment; green, rumen; blue, human GI tract). Bootstrap support values greater than 0.5 are displayed. Locations of putative gain and loss of functions are also shown on the trees. Stars mark the gain of butyric acid production capabilities (pink, butyrate kinase; orange, BCoAT). An alternative gain of butyrate kinase is marked with a pink X on the 16S tree (part A). Putative loss of sporulation capabilities is marked with a black bar. Strains classified as gut restricted based on shared gene clusters are underlined.