# Genetic Transmission of Componenets of the Human Gut Microbiome

> **NIH NIH R01** · CORNELL UNIVERSITY · 2020 · $81,365

## Abstract

Project Summary
The microbes that inhabit the human body are viewed as an integral component of our biology, and
microbiome variability has been found to result in differences in disease predisposition. The proposed
research will develop and apply methods to infer how variation in the human genome mediates
composition and function of the gut microbiome. To achieve this objective, we will pursue four specific
aims in an analysis of genome-wide SNP genotype data already available from the TwinsUK project to
identify genetic determinants of microbiome composition. For Specific Aim 1, we will use whole-
genome sequence data of the twins along with deep metagenomic sequencing of their gut
microbiomes to infer heritability and gene-specific associations with a) greater resolution taxonomic
data, and b) metabolic attributes of the bacterial community. These data are already in hand, and provide
unique opportunities to dissect the means by which variation in the human genome mediates gut
microbiome properties. For Specific Aim 2, we will infer individual strains in the gut microbiomes
from the metagenomics data, making use of the fact that our sequencing depth is sufficient to identify
clonal haplotypes of the most common ~50 bacterial species. The biological impacts of specific strains
can vary widely, and this strain-specific analysis is likely to be highly informative by improving specificity
and accuracy of associations between host genes and microbiome composition. For Specific Aim 3, we
will resample 1000 individuals from the original TwinsUK microbiome survey, and use this
information to identify attributes of the gut microbiome that are stable over time, and to test the
relationship between heritability and stability of microbes in the microbiome. For Specific Aim 4, we will
use the gnotobiotic mouse experimental system to dissect the effects of the heritable bacterium
Christensenella minuta on gut function as well has whole-organism physiology. The results of this
research will be used to establish links between regions of the human genome and composition of the
microbiome. The results of this study have the potential to reveal fundamental human host-microbe
interactions that may be applicable to the prevention and treatment of chronic inflammatory diseases.

## Key facts

- **NIH application ID:** 10248711
- **Project number:** 3R01DK093595-08S1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** ANDREW G CLARK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,365
- **Award type:** 3
- **Project period:** 2011-09-19 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248711

## Citation

> US National Institutes of Health, RePORTER application 10248711, Genetic Transmission of Componenets of the Human Gut Microbiome (3R01DK093595-08S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10248711. Licensed CC0.

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