Summary
The gut microbiome is a key modulator of immune and metabolic health. Human microbiome data is biased towards industrialized populations, providing limited understanding of the distinct and diverse non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing and strain cultivation on 351 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, bacteriophages, and eukaryotes, 43% of which are absent from existing unified datasets. Analysis of in situ growth rates, genetic pN/pS signatures, high-resolution strain tracking, and 124 gut-resident species vanishing in industrialized populations reveals differentiating dynamics of the Hadza gut microbiome. Industrialized gut microbes are enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource that expands our understanding of microbes capable of colonizing the human gut and clarifies the extensive perturbation brought on by the industrialized lifestyle.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Revised Figure 1 added to include more details about sample collection and computational pipeline; Much of original Figure 1 has become revised Figure 2; Figure 3 added to expand on implications of sequencing depth; Old Figure 2 has become revised Figure 4; Old Figure 3 has become revised Figure 5; Old Figure 4 has become revised Figure 6, which as been expanded to include a functional analysis of the Hadza gut microbiota. Supplemental files and figures updated accordingly.
