# Genomic and metabolomic foundations of human-microbial symbiosis in the gut

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $705,658

## Abstract

SUMMARY
A microbial perspective of human development provides opportunities to both expand and refine our definitions
of healthy postnatal growth. A corollary is that ensuring healthy microbiota development likely has long-term
beneficial effects on host physiology, metabolism, and immunity. Little is known about the mechanisms that
drive microbiota assembly (succession). Our central hypothesis is that the nutrient requirements of members of
different stages of community development, and that changes in nutrient availability in the diet/gut, are key
drivers of succession. Based on our previous studies, we postulate that (i) succession can be modeled in
gnotobiotic mice, (ii) the nutrient requirements of community members can be deduced from in silico metabolic
reconstructions based on their genome sequences; (iii) predictions from (ii) can be directly tested and refined
through analyses of young gnotobiotic mice colonized with defined consortia of human gut bacterial strains
representing different stages of community assembly. Based on our birth-cohort studies of healthy USA twins,
we will model succession using a collection of sequenced bacterial stains cultured from a single (‘formula-fed’)
cohort member. Strains have been grouped into consortia representing 3 stages of community development
[Stage 1 (S1; months 1-2; when ‘weedy organisms’ are able to rapidly occupy a previously empty gut
ecosystem), Stage 2 (S2, months 3-6; when organisms are rapidly acquired through dispersal from various
environmental reservoirs as infants consume a milk-dominated diet), Stage 3 (S3, months 7-24; a period where
fruits, vegetables and cereals become a more prominent part of the diet]. Our approach, described in 2 aims,
involves multi-omic analyses of succession as a function of the availability of specified dietary nutrients [amino
acids, B-vitamins (precursors of essential cofactors for myriad metabolic reactions), and carbohydrates
(primary source of carbon/energy). Young GF mice colonized with the different stage consortia, introduced
alone, together in various combinations, or in various sequences will be fed an ‘unmodified’ defined infant
formula (IF) diet or IF derivatives where the representation of 4 different amino acids, or 4 different B vitamins,
and several carbohydrates represented in fruits and vegetables are varied. The effects on consortium
members will be characterized by measurements of their relative and absolute abundances (to assess
competitiveness/fitness) in jejunum, cecum, colon, and feces and the results correlated with (i) amino acid, B
vitamin, carbohydrate concentrations in these different gut compartments (targeted mass spectrometry), (ii)
expression of genes involved in various metabolic pathways (microbial RNA-Seq), and (iii) our in silico
subsystems-based approach for predicting metabolic phenotypes/nutrient requirements. Our approach, based
on the ability to manipulate which organisms are introduced and when, under specified n...

## Key facts

- **NIH application ID:** 9962371
- **Project number:** 5R01DK030292-37
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JEFFREY I GORDON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $705,658
- **Award type:** 5
- **Project period:** 1982-01-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962371

## Citation

> US National Institutes of Health, RePORTER application 9962371, Genomic and metabolomic foundations of human-microbial symbiosis in the gut (5R01DK030292-37). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962371. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*