Functional Divergence in Gut Clostridia from Hadza Hunter-Gatherers Reveals Diet-Adapted Metabolic Machinery That Shapes Gut Ecology
- 1Stanford University
Abstract
Lifestyle changes associated with industrialization, including shifts in diet, are linked to extensive remodeling of the human gut microbiome. Investigating the gut microbiomes of traditional populations living non-industrialized lifestyles, such as the Hadza hunter-gatherers of Tanzania, therefore offers insight into bacterial taxa and functions depleted in industrialized microbiomes. Despite pronounced compositional differences that correspond to lifestyle, many commensal gut species are shared between industrialized and non-industrialized populations, raising a fundamental question of whether and how their functional repertoires diverge across contrasting gut environments. Here, by integrating strain-resolved metagenomics with culturomics and in vivo models, we identify phylogenetic and functional divergence within prevalent gut species shared between Hadza and industrialized populations, particularly among members of the Clostridia class. Dorea longicatena, prevalent across diverse human populations independent of lifestyle, is a poorly characterized member of Clostridia. Using strains of this D. longicatena isolated from either Hadza or industrialized human stool samples, we uncover metabolic pathways selectively enriched in Hadza strains, including machinery for utilizing plant-derived pectic polysaccharides. We further demonstrate that this Hadza-enriched polysaccharide-utilization machinery can be leveraged with its cognate dietary substrate to promote D. longicatena colonization within a model industrialized microbiota. Together, our findings reveal substantial functional divergence within gut bacterial species shared across lifestyles, providing a framework for identifying diet-responsive strains and pathways that may complement ecological and metabolic functions underrepresented in industrialized microbiotas.
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BibTeX
@misc{takeuchi2026functional,
title = {{Functional Divergence in Gut Clostridia from Hadza Hunter-Gatherers Reveals Diet-Adapted Metabolic Machinery That Shapes Gut Ecology}},
author = {T. Takeuchi and A. Reddy and E. K. Robinson and K. Kotaka and S. K. Higginbottom and E. D. Sonnenburg and J. L. Sonnenburg},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755216},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755216v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Functional Divergence in Gut Clostridia from Hadza Hunter-Gatherers Reveals Diet-Adapted Metabolic Machinery That Shapes Gut Ecology
AU - T. Takeuchi
AU - A. Reddy
AU - E. K. Robinson
AU - K. Kotaka
AU - S. K. Higginbottom
AU - E. D. Sonnenburg
AU - J. L. Sonnenburg
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755216
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755216v1
AB - Lifestyle changes associated with industrialization, including shifts in diet, are linked to extensive remodeling of the human gut microbiome. Investigating the gut microbiomes of traditional populations living non-industrialized lifestyles, such as the Hadza hunter-gatherers of Tanzania, therefore offers insight into bacterial taxa and functions depleted in industrialized microbiomes. Despite pronounced compositional differences that correspond to lifestyle, many commensal gut species are shared between industrialized and non-industrialized populations, raising a fundamental question of whether and how their functional repertoires diverge across contrasting gut environments. Here, by integrating strain-resolved metagenomics with culturomics and in vivo models, we identify phylogenetic and functional divergence within prevalent gut species shared between Hadza and industrialized populations, particularly among members of the Clostridia class. Dorea longicatena, prevalent across diverse human populations independent of lifestyle, is a poorly characterized member of Clostridia. Using strains of this D. longicatena isolated from either Hadza or industrialized human stool samples, we uncover metabolic pathways selectively enriched in Hadza strains, including machinery for utilizing plant-derived pectic polysaccharides. We further demonstrate that this Hadza-enriched polysaccharide-utilization machinery can be leveraged with its cognate dietary substrate to promote D. longicatena colonization within a model industrialized microbiota. Together, our findings reveal substantial functional divergence within gut bacterial species shared across lifestyles, providing a framework for identifying diet-responsive strains and pathways that may complement ecological and metabolic functions underrepresented in industrialized microbiotas.
ER -