# Population Genomics of Host-Microbiome Interactions

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $399,519

## Abstract

Population Genomics of Host-Microbiome Interactions
 There is wide variation in the composition of the microbial communities that colonize the human body
across individuals and populations, and this variation has been associated with numerous host traits and
diseases. Understanding the factors that influence this variation, and the mechanism by which this variation
affects host traits, is of central goal in human disease research. Although some of the variation in the
microbiome is controlled by host genetics, we know very little about the genomic factors that control the
interaction between humans and the microbiome and their effect on complex human disease. Disentangling
genetic from environmental effects on the microbiome is challenging, and the microbiome is usually profiled in
a single time point, which doesn’t account for microbiome longitudinal variation. Moreover, most of our
knowledge on host-microbiome interactions consists of correlational associations, and we do not know how
inter-individual and inter-population variation in microbiome composition affects host gene regulation.
 My laboratory’s research aims 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. My lab’s research program for the next five years is designed
to answer fundamental questions about the genomic basis of host-microbiome interactions via three broad,
complementary Project Areas, aiming to: (1) develop computational techniques to integrate microbiome and
host genomic data, and apply these methods to achieve a systems-level understanding of host-microbiome
interactions across populations and disease states; (2) characterize the heritability of functional components of
the microbiome (microbial genes, strains, and pathways) and assess the effect of life-long longitudinal
microbiome dynamics on host physiology in a primate model system; and (3) use novel in-vitro and ex-vivo
systems to understand the causal effect of inter-individual and 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 factors in the gut across populations, environments, and diseases; a characterization
of how microbiome longitudinal dynamics, as well as genes, pathways, and strains are controlled by host
genetic; and a description of the mechanism with which 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 enable development of microbiome-based therapeutics and diagnostics that
improve h...

## Key facts

- **NIH application ID:** 10847337
- **Project number:** 5R35GM128716-07
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Ran Blekhman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,519
- **Award type:** 5
- **Project period:** 2018-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847337

## Citation

> US National Institutes of Health, RePORTER application 10847337, Population Genomics of Host-Microbiome Interactions (5R35GM128716-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10847337. Licensed CC0.

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