# C. elegans as a model for studying genetic control of microbiota structure and function

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $360,718

## Abstract

Project Summary. Animal microbiotas are increasingly recognized as essential for host health. The gut
microbiota is the richest, and was shown to contribute to diverse host functions. Perturbations in microbiota
composition are associated with human disease, raising interest in manipulating the microbiota to promote
healthier living or treat pathology. However, current understanding of the factors that shape microbiota
composition is still lacking. Studies in vertebrates characterized the effects of diet on microbiota composition,
but much less is known about the role of genetic factors, due to high inter-individual variability attributed to
genetic heterogeneity. As an alternative, C. elegans enables work with genetically homogenous populations,
averaging-out inter-individual variation to discern gene effects. We have established C. elegans as a new model
for studying host-microbiota interactions, identifying a reproducible gut microbiota, with commensals that
enhance host development and immunity. Our results demonstrate significant contributions of host genetics to
shaping of microbiota structure and function and to preferential colonization by beneficial commensals, and
identified a role for TGFb signaling in controlling abundance of a beneficial Enterobacter commensal, preventing
pathogenic dysbiosis. The goal of the proposed plan is to develop this model to expedite discovery and
characterization of host genes that shape microbiota composition and function.
Two complimentary experimental pipelines were established in the lab: one takes advantage of composted soil
microcosms to grow worms in natural-like environments, using 16S deep sequencing to compare their gut
microbiotas to those in their environment, and enabling isolation of environmentally-derived gut commensals;
the second, uses synthetic microbiotas consisting of 30 gut isolates, offering tight control over environmental
diversity, and interrogated using qPCR with taxa-specific primers. Combining the two approaches, the proposed
plan aims to: 1) Characterize TGFb-Enterobacter interactions, determining their specificity, modulation by
environmental factors, and the mechanisms underlying their effects on microbiota composition, using it as a case
study for detailed investigation of gene-microbiota interactions. 2) Use worm mutants for candidate genes with
diverse functions, to characterize gene contributions to microbiota composition and function. 3) Mutagenize
worms to identify genes involved in host selectivity toward beneficial commensals; expression of two different
fluorescent proteins in two Enterbacter commensals from different Caenorhabditis species revealed preferential
colonization of C. elegans by its own beneficial commensal when presented in a mix with a similar C. briggsae
commensal; mutants would be sought that do not show this preference.
Harnessing the genetic power of C. elegans to studying host-microbiota interactions - establishing the
methodologies and commensal ...

## Key facts

- **NIH application ID:** 9942536
- **Project number:** 5R01OD024780-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Michael Shapira
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $360,718
- **Award type:** 5
- **Project period:** 2018-09-06 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942536

## Citation

> US National Institutes of Health, RePORTER application 9942536, C. elegans as a model for studying genetic control of microbiota structure and function (5R01OD024780-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9942536. Licensed CC0.

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