Biology subjects

Sonnenburg, E. D.

Publications and source records attributed to Sonnenburg, E. D..

7 recordsLinked to original sources

bioRxiv2026

Functional Divergence in Gut Clostridia from Hadza Hunter-Gatherers Reveals Diet-Adapted Metabolic Machinery That Shapes Gut Ecology

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, reshaping intestinal and portal-vein metabolite profiles. 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.

microbiology↗

bioRxiv2025

Prehistoric Global Migration of Vanishing Gut Microbes With Humans

The gut microbiome is crucial for health and greatly affected by lifestyle. Many microbes common in non-industrialized populations are disappearing or extinct in industrialized populations. Understanding which microbes have been long-term residents of the human gut, and may have co-evolved with humans, has implications for the importance of microbial biodiversity loss for health. However, the genetic complexities of microbial evolution and the plasticity of gut microbiome composition have made it challenging to define these long-term associations. Here, we performed deep metagenomic sequencing of the Tsimane horticulturalists of Bolivia and compared their gut microbiomes with the Hadza hunter-gatherers of Tanzania. These two populations, whose ancestors were separated for tens of thousands of years, share 1,231 microbial species, most of which are absent in industrialized populations. Population genetic analyses in 636 of these shared species revealed patterns of microbial divergence and gene flow consistent with prehistoric human co-migration, with estimated split times that approximately align with human migration out of Africa and into the Americas. Our findings indicate that a diverse gut microbiome co-migrated with humans around the globe, persisting over millennia. However, many of these species are now vanishing in industrialized populations, and the consequences for human health remain uncertain.

microbiology↗

bioRxiv2023

Hadza Prevotella Require Diet-derived Microbiota Accessible Carbohydrates to Persist in Mice.

Industrialization has transformed the gut microbiota, reducing the prevalence of Prevotella relative to Bacteroides. Here, we isolate Bacteroides and Prevotella strains from the microbiota of Hadza hunter-gatherers of Tanzania, a population with high levels of Prevotella. We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence of Prevotella copri but not Bacteroides thetaiotaomicron in vivo. Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that Hadza Prevotella strains specialize in degrading plant carbohydrates, while Hadza Bacteroides isolates use both plant and host-derived carbohydrates, a difference mirrored in Bacteroides from non-Hadza populations. When competing directly, P. copri requires plant-derived MACs to maintain colonization in the presence of B. thetaiotaomicron, as a no MAC diet eliminates P. copri colonization. Prevotellas reliance on plant-derived MACs and Bacteroides ability to use host mucus carbohydrates could explain the reduced prevalence of Prevotella in populations consuming a low-MAC, industrialized diet. Statement on work with indigenous communitiesIn order to acquire scientific knowledge that accurately represents all human populations, rather than only reflecting and benefiting those in industrialized nations, it is necessary to involve indigenous populations in research in a legal, ethical, and non-exploitative manner (Abdill et al., 2022; Green et al., 2020). Here, we isolated live bacterial strains from anonymized fecal samples collected from Hadza hunter-gatherers in 2013/2014 (Fragiadakis et al., 2019; Merrill et al., 2022; Smits et al., 2017). Samples were collected with permission from the Tanzanian government, National Institute of Medical Research (MR/53i 100/83, NIMR/HQ/R.8a/Vol.IX/1542), the Tanzania Commission for Science and Technology, and with aid from Tanzanian scientists. A material transfer agreement with the National Institute for Medical Research in Tanzania specifies that collected samples are solely to be used for academic purposes. For more information on the consent practices followed, and our ongoing work to communicate the results of these projects to the Hadza, please see (Merrill et al., 2022; Olm et al., 2022).

microbiology↗

bioRxiv2022

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

Infant microbiome assembly is intensely studied in infants from industrialized nations, but little is known about this process in populations living non-industrialized lifestyles. In this study we deeply sequenced infant stool samples from the Hadza hunter-gatherers of Tanzania and analyzed them in a global meta-analysis. Infant microbiomes develop along lifestyle-associated trajectories, with over twenty percent of genomes detected in the Hadza infant gut representing phylogenetically diverse novel species. Industrialized infants, even those who are breastfed, have microbiomes characterized by a paucity of Bifidobacterium infantis and gene cassettes involved in human milk utilization. Strains within lifestyle-associated taxonomic groups are shared between mother-infant dyads, consistent with early-life inheritance of lifestyle-shaped microbiomes. The population-specific differences in infant microbiome composition and function underscore the importance of studying microbiomes from people outside of wealthy, industrialized nations. Recognition of work on indigenous communitiesResearch involving indigenous communities is needed for a variety of reasons including to ensure that scientific discoveries and understanding appropriately represent all populations and do not only benefit those living in industrialized nations. Special considerations must be made to ensure that this research is conducted ethically and in a non-exploitative manner. In this study we performed deep metagenomic sequencing on fecal samples that were collected from Hadza hunter-gatherers in 2013/2014 and were analyzed in previous publications using different methods (1, 2). A material transfer agreement with the National Institute for Medical Research in Tanzania ensures that stool samples collected are used solely for academic purposes, permission for the study was obtained from the National Institute of Medical Research (MR/53i 100/83, NIMR/HQ/R.8a/Vol.IX/1542) and the Tanzania Commission for Science and Technology, and verbal consent was obtained from the Hadza after the studys intent and scope was described with the help of a translator. The publications that first described these samples included several scientists and Tanzanian field-guides as co-authors for the critical roles they played in sample collection, but as no new samples were collected in this study, only scientists who contributed to the analyses described here were included as co-authors in this publication. It is currently not possible for us to travel to Tanzania and present our results to the Hadza people, however we intend to do so once the conditions of the COVID-19 pandemic allow it.

microbiology↗

bioRxiv2022

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

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.

microbiology↗

bioRxiv2019

Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight

With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight loss strategies, coupled with an understanding of how they interface with host physiology. While diet is a critical and promising area of focus, it has been difficult to identify diets that are broadly effective in long-term weight management. To explore the interaction between specific diets and bacteria within the gut, we tracked microbiota composition over a 12-month period as part of a larger dietary intervention study of participants consuming either a low-carbohydrate or low-fat diet. While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota three months after the start of the intervention; some of these changes were diet-specific and others tracked with weight loss. After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study. These results suggest a resilience to perturbation of the microbiomes starting state. When considering the established contribution of obese-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to host physiology.

microbiology↗

bioRxiv2018

Links between environment, diet, and the hunter-gatherer microbiome

The study of traditional populations provides a view of human-associated microbes unperturbed by industrialization, as well as a window into the microbiota that co-evolved with humans. Here we discuss our recent work characterizing the microbiota from the Hadza hunter-gatherers of Tanzania. We found seasonal shifts in bacterial taxa, diversity, and carbohydrate utilization by the microbiota. When compared to the microbiota composition from other populations around the world, the Hadza microbiota shares bacterial families with other traditional societies that are rare or absent from microbiotas of industrialized nations. We present additional observations from the Hadza microbiota and their lifestyle and environment, including microbes detected on hands, water, and animal sources, how the microbiota varies with sex and age, and the shortterm effects of introducing agricultural products into the diet. In the context of our previously published findings and of these additional observations, we discuss a path forward for future work.

microbiology↗