# National Gnotobiotic Resource Center

> **NIH NIH P40** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $60,401

## Abstract

Resident microbiota influence physiologic responses in many organs and are linked to many inflammatory,
metabolic, neoplastic and behavioral disorders. Altered microbiota (dysbiosis) is associated with these
conditions by vastly improved deep sequencing, metabolomic and analytic techniques. However, functional
consequences, the primary vs. secondary nature of these compositional changes and role of individual
bacterial species and combinations remain unknown. These functional properties are mechanistically
addressed in gnotobiotic mice by precisely manipulating the microbiota in selectively colonized germ-free (GF)
wild-type and genetically-engineered inbred mice with single or multiple resident or pathogenic microbial
strains. Fecal microbial transplants (FMT) transfer healthy or diseased human or experimental animal’s fecal
microbiota to GF mice to explore functional properties of dysbiotic complex bacterial communities. However,
microbial and clinical heterogeneity between individuals with human complex disease are enormous and
greatly affect FMT results. Most investigators use single or small numbers of fecal donors for FMT, leading to
marked variability in results from different human donors. An important unmet research need is an easily
accessible source of broadly representative and fully characterized human fecal samples for colonizing GF
mice t achieve consistent reproducible results. Human FMT into gnotobiotic mice is a popular approach to test
in vivo functional properties of dysbiotic bacterial communities from diseased patients and enhance clinical
relevance of murine preclinical therapeutic models. We show low efficiency transfer of human fecal bacteria to
GF mice, but enhanced transfer efficiency with this material from the murine recipient to another GF mouse.
Transplant of this mouse-adapted (MA) human microbiota to other mice yields more reproducible colitis than
did FMT of the original pooled human fecal samples, but with retention of the transferred human phenotype.
Other uncertainties that limit reproducibility of human FMT to GF mice are the variable methods of fecal
microbial transfer; frequency of administration, duration of equilibration after shipping mice prior to FMT, since
most of our users do not have local gnotobiotic facilities to maintain sterility after receiving our mice, and type
of housing after transfer. Carefully dissecting these variables will develop optimal protocols for handling and
housing mice before and after FMT. We hypothesize that human fecal bacterial transfer to GF mice can be
improved by optimizing transfer techniques and transferring fully characterized mouse-adapted pooled human
fecal transplants into gnotobiotic inbred mice will yield highly reproducible results and stable phenotypes in
recipient mice. Aim: Improve fecal transfer techniques, optimize housing conditions for recipient mice
and characterize pooled complex mouse-adapted human fecal microbial communities from healthy
donors and th...

## Key facts

- **NIH application ID:** 10936333
- **Project number:** 2P40OD010995-21
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Ryan B Sartor
- **Activity code:** P40 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $60,401
- **Award type:** 2
- **Project period:** 2003-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936333

## Citation

> US National Institutes of Health, RePORTER application 10936333, National Gnotobiotic Resource Center (2P40OD010995-21). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10936333. Licensed CC0.

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