Ultra-deep Sequencing of Hadza Hunter-Gatherers Recovers Vanishing Gut Microbes

Abstract

The gut microbiome has been identified as a key to immune and metabolic health, especially in industrialized populations. Non-industrialized individuals harbor more diverse microbiomes and distinct bacterial lineages, but systemic under-sampling has hindered insight into the extent and functional consequences of these differences. Here, we performed ultra-deep metagenomic sequencing and laboratory strain isolation on fecal samples from the Hadza, hunter-gatherers in Tanzania, and comparative populations in Nepal and California. We recover 94,971 total genomes of bacteria, archaea, bacteriophage, and eukaryotes, and find that 43% are novel upon aggregating with existing unified datasets. Analysis of in situ growth rates, genetic pN/pS signatures, and high-resolution strain tracking reveal dynamics in the hunter-gatherer gut microbiome that are distinct from industrialized populations. Industrialized versus Hadza gut microbes are enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. We use phylogenomics to reveal that global spread of the spirochaete Treponema succinifaciens parallels historic human migration prior to its extinction in industrialized populations. When combined with a detailed definition of gut-resident strains that are vanishing in industrialized populations, our data demonstrate extensive perturbation in many facets of the gut microbiome brought on by the industrialized lifestyle.

Evolutionary ecology of microbial populations inhabiting deep sea sediments associated with cold seeps

“…However, these conclusions were only based on abundant populations from MOB, ANME and SRB, genomic microdiversification of other species at lower abundance levels can still play important functional roles was not evaluated due to relatively shallow sequencing 5 . Deeper sequencing is therefore needed to depict a full picture of microdiversity within microbial populations in deep sea sediments 57 .…”

Robust Variation in Infant Gut Microbiome Assembly Across a Spectrum of Lifestyles

“…S5C) . To assess prevalence via read mapping, MAGs were integrated with genomes recovered from Hadza adults ( 20 ) and public genomes from the human gut ( 21 ) into a comprehensive database of 5,755 species-representative genomes (see methods for details). Overall, 23.4% of microbial species detected in the Hadza infants represent novel species (Table S3) .…”

Codiversification of gut microbiota with humans

“…Cultured isolates of H. pylori show spatial patterns of strain diversity consistent with human migration patterns ( 13 ). A few prevalent gut microbial species, including Prevotella copri , are also thought to have tracked human migration, given how patterns of metagenome-derived strain variation mapped onto continents ( 4 – 6 ). Strain distributions that map onto human migration patterns are suggestive of codiversification, as geographic origins tend to reflect human genetic origins, especially at the continental level ( 14 , 15 ).…”