# Characterizing the dynamic operations of model human gut communities in gnotobiotic mice and piglets

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $608,910

## Abstract

PROJECT SUMMARY
DK70977 retains its focus on gnotobiotic models of the dynamic operations the human gut microbiota, and the
development of new experimental designs/tools to analyze how dietary components, specifically different
prebiotic polysaccharides added to diets representative of those consumed in the USA, shape microbial
community structure/function. It is based on the following advances and leverages a partnership between 2
labs with complementary expertise. (1) Methods for creating clonally arrayed sequenced `personal' culture
collections that capture the majority of bacterial taxa present in a human fecal microbiota sample. (2) Finding
that culture collections from twins stably discordant for obesity transmit the donor's discordant adiposity
phenotypes plus obesity-associated metabolic abnormalities to germfree (GF) mice. Co-housing results in
invasion of specific bacterial species from the lean (Ln) community into the guts of cagemates harboring Ob
co-twin's culture collection, preventing obesity and associated metabolic abnormalities. Invasion, principally by
members of the Bacteroides occurs with a representative USA diet low in saturated fats/high fruits-vegetables
diet (LoSF/HiFV) but not with a HiSF/LoFV diet. (3) Methods for performing genome-wide transposon
mutagenesis of multiple Bacteroides strains and simultaneously identifying genes/metabolic pathways that
confer their fitness in specified diet/community contexts (multi-taxon insertion sequencing, INSeq). (4) Methods
for generating GF piglets. We will pursue 2 aims. Aim 1, Perform diet oscillation studies in Ln-colonized mice
fed 160 different HiSF/LoFV diets supplemented with 40 different purified plant polysaccharides (PPS) in
varying doses, some from the waste-streams of commercial food processing, and identify PPS that produce
the greatest increase in abundance of a single targeted Bacteroides (`high selectivity, large effect size lead) or
significant increases in the greatest number of targeted Bacteroides (`broad range, significant effect size lead).
Followup mechanistic studies using (i) these leads, fed monotonously at different doses, and in diet oscillations
of different periodicity, plus (ii) multi-taxon INSeq, microbial RNA-Seq, new methods for multiplex quantitative
proteomics, and metabolomics, are intended to provide new definitions/insights about niche, syntrophic
partnerships, foodwebs, competitiveness, and their impact on community/host metabolism. Leads will also be
tested with the Ob collection supplemented with Bacteroides invaders. Aim 2, Application of these methods to
gnotobiotic piglets, colonized with these defined communities, fed HiSF/LoFV ± PPS leads and gavaged with
`artificial microscopic nutrient platforms' consisting of fluorescently-labeled paramagnetic beads coated with
different PPS, that can be retrieved from gut samples by FACS, should provide an unprecedented level of
spatial and temporal detail of how community structure and function v...

## Key facts

- **NIH application ID:** 9971518
- **Project number:** 5R01DK070977-15
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JEFFREY I GORDON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $608,910
- **Award type:** 5
- **Project period:** 2005-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971518

## Citation

> US National Institutes of Health, RePORTER application 9971518, Characterizing the dynamic operations of model human gut communities in gnotobiotic mice and piglets (5R01DK070977-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971518. Licensed CC0.

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