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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R01ES034012&format=word)
| Principal Investigator: Shapira, Michael | |
|---|---|
| Institute Receiving Award | University Of California Berkeley |
| Location | Berkeley, CA |
| Grant Number | R01ES034012 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 20 Sep 2022 to 31 Aug 2025 |
| DESCRIPTION (provided by applicant): | 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 adaptation to xenobiotic pressure. The proposed plan will explore how readily this happens, how it happens, and what are the trade-offs. |
| Science Code(s)/Area of Science(s) |
Primary: 68 - Microbiome Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | See publications associated with this Grant. |
| Program Officer | Anika Dzierlenga |