Subspecies in the global human gut microbiome

Abstract

Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large‐scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture‐independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72% of the total assigned microbial abundance, single‐nucleotide variation clearly indicates the existence of sub‐populations (here termed subspecies). A single subspecies (per species) usually dominates within each host, as expected from ecological theory. At the global scale, geographic distributions of subspecies differ between phyla, with Firmicutes subspecies being significantly more geographically restricted. To investigate the functional significance of the delineated subspecies, we identified genes that consistently distinguish them in a manner that is independent of reference genomes. We further associated these subspecies‐specific genes with properties of the microbial community and the host. For example, two of the three Eubacterium rectale subspecies consistently harbor an accessory pro‐inflammatory flagellum operon that is associated with lower gut community diversity, higher host BMI, and higher blood fasting insulin levels. Using an additional 676 human oral samples, we further demonstrate the existence of niche specialized subspecies in the different parts of the oral cavity. Taken together, we provide evidence for subspecies in the majority of abundant gut prokaryotes, leading to a better functional and ecological understanding of the human gut microbiome in conjunction with its host.

Evolutionary dynamics of bacteria in the gut microbiome within and across hosts

“…Even at this coarse, core-genome-wide level, the genetic distances vary over several orders of magnitude. Some species show multiple peaks of divergence for high values of d, consistent with the presence of subspecies [36], ecotypes [53,54], or other strong forms of population structure. These coarse groupings have been observed previously and are not our primary focus here.…”

“…While traditional amplicon sequencing provides limited resolution to detect within-species evolution [30], whole-genome shotgun metagenomic sequencing is starting to provide the raw polymorphism data necessary to address these questions [31]. In particular, several referencebased approaches have been developed to detect genetic variants within individual species in larger metagenomic samples [31][32][33][34][35][36]. While these approaches enable strain-level comparisons between samples, they have also documented substantial within-species variation in individual metagenomes [31,35,37].…”

Human microbiome aging clocks based on deep learning and tandem of permutation feature importance and accumulated local effects

“…The corresponding project IDs are: ERP005534, SRP008047, ERP009422, ERP004605, ERP002061, ERP002469, ERP019502, SRP002163, ERP003612, ERP008729. [46][47][48][49] Only healthy individuals with age metadata available were included in this study. These individuals were from Austria, China, Denmark, France, Germany, Kazakhstan, Spain, Sweden and USA.…”

Is adolescence the missing developmental link in Microbiome–Gut–Brain axis communication?

“…For example, in a pre‐ and post‐fMRI design, compared to baseline activity, women who received a 4‐week probiotic treatment had reduced resting‐state functional activity in regions involved in emotion and sensation processing, including the insula, somatosensory cortex, as well as the prefrontal cortex, parahippocampal gyrus, precuneus, and basal ganglia (Tillisch et al, ). In follow‐up experiments, Tillisch et al () also demonstrated that an individual's functional and structural connectivity could be characterized by the type of prominent bacteria in their microbiome (a clustering analysis typically referred to as “enterotyping”; see Costea et al () for a review on the debate surrounding this methodology). Women in the microbial cluster predominated by Prevotella (vs. Bacteroides ) had decreased hippocampal activity and increased functional brain connectivity between brain regions involved in emotional and attentional sensory processing.…”