# Defining and Reconstructing the Human Ancestral Microbiome

> **NIH NIH DP1** · STANFORD UNIVERSITY · 2021 · $1,099,000

## Abstract

The gut microbiota is an integrated part of human biology and has coevolved with us, passing from generation to
generation for millions of years. Therefore, the species that are likely to have biology most compatible with the human
genome are specific and not a random collection that we can assemble from the surrounding environment and let the
prevailing selective forces shape. The plasticity of the gut microbiota offers tremendous potential for therapeutic
manipulation, but this malleability can translate into species-loss during perturbations like those that have accompanied
industrialization. The microbiota of people living a Western lifestyle differs substantially from that of traditional
populations whose lifestyles are relatively free of the forces of modernization. These “traditional” microbiotas contain
taxa that are common to traditional populations on different continents yet are absent or exceedingly rare among people in
the industrialized world. This project aims to understand the species and genes that define and differentiate the
microbiome of traditional populations. A primary goal of this research is to pursue a deep biological understanding of how
compositional and functional differences between the traditional microbiota and Western microbiota affect human
biology. Using existing de-identified archived stool samples from hunter-gatherers, a variety of tools will be applied
including deep metagenomic sequencing, isolation and characterization of microbial species that are absent or rare in the
Western gut, gnotobiotic mouse models, and molecular genetics. This study will result in an important, novel
understanding of the human microbiome, one that addresses the fundamental question of what defines the microbiomes
that our species evolved with. Investigating the microbiome from an evolutionary perspective will yield insight into how
missing components of our biology may be complemented via gut microbiota colonization. This approach will
significantly contribute to preventing and treating a spectrum of non-communicable chronic diseases.

## Key facts

- **NIH application ID:** 10221605
- **Project number:** 5DP1AT009892-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JUSTIN L SONNENBURG
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,099,000
- **Award type:** 5
- **Project period:** 2017-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221605

## Citation

> US National Institutes of Health, RePORTER application 10221605, Defining and Reconstructing the Human Ancestral Microbiome (5DP1AT009892-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221605. Licensed CC0.

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