# The role of the gut microbiome in host adaptation to environmental xenobiotics - mechanisms and long-term consequences

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $1,083,375

## Abstract

Project summary. The gut microbiome plays important roles in host health and fitness. In the human gut,
microbes are estimated to have ~100-fold more genes than in the host genome, and throughout animal
evolution, bacterial biochemical diversity has been instrumental in enabling hosts adapt to new diets and
environments. The current Anthropocene is posing new challenges to ecosystems and the communities living
in them. Among those is xenobiotic usage and pollution, including antibiotics and pesticides, some of which
are tightly regulated for known toxic effects, the toxicity of others is still debated. The gut microbiome has
been shown to respond to xenobiotic exposures, and anecdotal evidence demonstrates that microbiome
adaptation and exchanges with the environment can help animals adapt to the new stress within one
generation. However, microbiome adaptation may have trade-offs as changes to microbiome composition, or
dysbiosis, are often associated with pathology. We hypothesize that the pressure of human-made xenobiotics
promotes pervasive microbiome-assisted adaptation and that the associated changes are a yet
underappreciated cause for human variation and pathology. We propose to use the C. elegans model to
explore the pervasiveness of microbiome-assisted adaptation to pesticides, the underlying mechanisms and
the long-term consequences for host health throughout its life. We have established C. elegans as a model
for microbiome research, enabling work with natural-like microcosms, synthetic communities and
fluorescently-labeled commensals, and showed that similar to vertebrate models, worms harbor characteristic
microbiomes that reflect the environmental availability of bacteria, which are further shaped by host genetics.
Preliminary experiments with an antibiotic (to ensure effects on bacteria) that is also toxic to worms, readily
demonstrated gut microbiome adaptation that protected the host, and further showed that adapted
microbiomes were not simply enriched with the most environmentally-available strain, but that host filtering,
modulated by the toxin, shaped them. The proposed plan will start with a characterization of this example of
adaptation, to gain insights into pivotal mechanisms of microbiome-assisted adaptation. However, the bulk of
the proposed work will focus on adaptation to commonly used herbicides and insecticides (toxic to worms
too), which are associated with pathology in humans, but are poorly understood. We will identify protective
bacteria, study the course of adaptation and the role of the host in determining it, and characterize long-term
consequences focusing on phenotypes associated with altered metabolism, immunity and lifespan.
Recent efforts are invested in looking into the effects of various pesticides on the gut microbiome, assuming
that those may have detrimental consequences. Our hypothesis is that this is far more common than currently
appreciated, and that this is part of the broader process of host ad...

## Key facts

- **NIH application ID:** 10421956
- **Project number:** 1R01ES034012-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Michael Shapira
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,083,375
- **Award type:** 1
- **Project period:** 2022-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10421956

## Citation

> US National Institutes of Health, RePORTER application 10421956, The role of the gut microbiome in host adaptation to environmental xenobiotics - mechanisms and long-term consequences (1R01ES034012-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10421956. Licensed CC0.

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