# Population Genomics of Host-Microbiome Interactions

> **NIH NIH R35** · UNIVERSITY OF MINNESOTA · 2020 · $369,161

## Abstract

Population Genomics of Host-Microbiome Interactions
 The composition of the microbial communities that colonize the human body varies widely across
individuals and populations, and has been associated with numerous host traits and diseases. Although the
microbiome is influenced by environmental factors, a strong host genetic factor is also expected to control the
interaction between humans and the microbiome. Understanding the relative role of genetic and environmental
factors in host-microbiome interactions is a central goal in human disease research. However, we know very
little about the genomic factors that control the interaction between humans and the microbiome and their
effect on complex human disease. It is often difficult to disentangle genetic from environmental effects on the
microbiome, and studies only consider the microbiome in a single time point, which could be problematic given
the microbiome can vary dramatically day-to-day and throughout an individual's life. Moreover, as most
microbiome studies identify correlations, we do not know how inter-individual and inter-population variation in
microbiome composition affects host physiology.
 In this proposal, I outline a long-term research strategy to address these critical gaps in knowledge.
Research in my lab is based on the hypothesis that the microbiome can be considered a quantitative trait, and
thus we can directly map host genomic factors controlling the variation in the microbiome, as well as identify
individual host genes and pathways that are regulated by the microbiome. Here, I outline my lab's research
program for the next five years, designed to answer fundamental questions about the genetic basis of host-
microbiome interactions via three broad, complementary Project Areas, aiming to: (1) collect and integrate host
and microbiome genomic data to achieve a systems-level understanding of host-microbiome molecular
interactions in the colon; (2) characterize the heritability of life-long longitudinal microbiome dynamics in a
primate model system; and (3) use novel in vitro and ex vivo systems to understand the effect of inter-
population variation in the microbiome on host gene regulation and describe the underlying regulatory
mechanism.
 The proposed research program will provide a systems-level view of the molecular interactions between
host genes and microbial taxa, genes, and pathways in the gut; a characterization of how microbiome
dynamics and taxa are controlled by host genetic variation; and a description of the mechanism with which the
microbes regulate host genes. These results would transform our understanding of the interplay between
human genomics and the microbiome, explain how this interaction affects disease, and would enable
development of microbiome-based therapeutics and diagnostics that improve human health.

## Key facts

- **NIH application ID:** 9984441
- **Project number:** 5R35GM128716-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Ran Blekhman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,161
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984441

## Citation

> US National Institutes of Health, RePORTER application 9984441, Population Genomics of Host-Microbiome Interactions (5R35GM128716-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984441. Licensed CC0.

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