# Evolutionary Dynamics of the Human Gut Microbiome During Colonization

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $400,010

## Abstract

PROJECT SUMMARY
The human gut microbiome is intimately connected with health, with disruptions of its ecological composition
associated with numerous diseases. Manipulations of the microbiome via fecal microbiome transplants (FMTs),
in which microbial strains derived from healthy donor stool are introduced to a patient's gut community, have
been found to be effective treatments for certain diseases, but less effective for others. In several cases in
which FMTs fail to resolve a disease, invading strains fail to colonize, but it is unknown why, and even when
strains do colonize, a healthy clinical outcome still is not guaranteed. Experimental evolution studies in mouse
and bee microbiomes have shown that strains invading a host rapidly adapt, enabling colonization via physical
adherence to host cells, competition with resident strains, and evasion of the host immune system. Despite this
strong experimental support for the importance of adaptation during colonization, its role in the human gut
microbiome has received little attention. Recently, we and others found that microbiome can evolve rapidly on
months and even days, but the impacts of this rapid pace of evolution on the colonization process remains
unknown. The main roadblock to linking adaptation and colonization lies in the statistical challenges of
quantifying the full landscape of adaptations from noisy metagenomic data. Here I propose to develop new
statistical methods that elucidate the evolutionary processes relevant for colonization in the
microbiome and apply them to one of the largest datasets of FMT recipients.
My lab's main goal is to understand how microbiomes evolve in a range of contexts and timescales. To this
end, the overarching objective of my proposed MIRA research program is to elucidate the evolutionary
processes that permit colonization of a strain. To fully quantify the mode, tempo, and targets of evolution in the
gut microbiome and their relevance to colonization, we will develop novel methodology capable of detecting
evolutionary events that are undetectable presently, including evolutionary changes (1) arising within hosts on
short timescales and (2) across hosts on longer time scales. To illustrate the potential of our statistical
innovations, we will study FMT recipients given that the identities of invading versus resident strains can be
easily distinguished. However, FMTs represent an example of a more general phenomenon of colonization
relevant to a range of cohorts and questions that my lab is studying, including the role of evolution in infants
experiencing an influx of microbes at birth, strain turnover during consumption of antibiotics and probiotics, and
spatial segregation of evolutionary adaptations needed for colonization along the gut. In sum, successful
completion of this work will not only generate statistical innovations needed to quantify evolution in the
microbiome, but also elucidate the importance of evolution in colonization, knowledge that pr...

## Key facts

- **NIH application ID:** 10896972
- **Project number:** 5R35GM151023-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Nandita Garud
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,010
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896972

## Citation

> US National Institutes of Health, RePORTER application 10896972, Evolutionary Dynamics of the Human Gut Microbiome During Colonization (5R35GM151023-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10896972. Licensed CC0.

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