Pathfinder Innovation Project – Does the Microbiome Influence More than Just our Gut?

By Tamara Tal

Did you know that tgraphic: a man and woman hold up beakers under the sentence"pathfinder innovation presents: meet the innovatorshere are an estimated 100 trillion microbes living on, and in, the human body? These microbes are everywhere – they coat our skin, live in our hair, and carpet our gut.  The community of bacteria that line our gut, known as the gut microbiota, expands our ability to process food and chemicals far beyond what the human genome encodes, and functions as a so-called “second genome.”

A group photo of the project team.

The project team.
Pictured front: Charles Wood, Tamara Tal (author), Alexander Gearhart . Pictured back: Mark Strynar, Drake Phelps. Not pictured: Doris Betancourt, Nichole Brinkman, Scott Keely, Charlene McQueen, Jeanene Olin, and Jon Sobus

Many studies have reported that microbiota are required for normal development. What’s more, changes to the human microbiome have been associated with multiple diseases like obesity, asthma, diabetes, and multiple sclerosis. Importantly for EPA, some studies are beginning to reveal that microbiota can detoxify or bioactivate environmental chemicals. Basically, those little microbes are doing a lot for us, but we still don’t understand how it all works.

In 2014, our team (pictured left) applied for a Pathfinder Innovation Project (PIP) to study the microbiome and how it relates to chemical safety. The PIP program is an internal competition for EPA scientists to receive time to explore their biggest ideas in environmental research. The key goal of this work is to better understand whether the toxicity of environmental chemicals is modified by gut microbes.

To do this, we developed a zebrafish model to test whether chemical toxicity is reliant on host-associated microbiota. Zebrafish are a small freshwater fish that develop rapidly after birth and are 70% similar in genetic makeup to humans. Since our initial proposal, we have demonstrated that this model can be used to rapidly test whether chemical toxicity is shaped by microbiota by comparing the effects of chemical exposures in sterile and colonized zebrafish. The PIP program has supported this work every step of the way.

A microscopic picture of a zebra fish

4 day old sterile zebrafish larva colonized with fluorescent bacteria (A. veronii HM21: dTomato)

Entering our third cycle of PIPs, the team is now working on a long-term effort that will allow us to learn more about how the microbiome impacts our body’s ability to process chemicals and thereby affect brain development. If we find that resident microbes change the way we process chemicals or that chemical exposures disrupt brain development that is controlled by normal microbial colonization, the way that we assess these chemicals may need to be re-examined.

Read the blog Transforming Science and Technology with Pathfinder Innovation Projects to learn more about the program.

 

About the Author: Tamara Tal is a Biologist in NHEERL’s Integrated Systems Toxicology Division. The Tal lab studies whether host-associated microbiota modify the developmental toxicity of environmental chemicals. The group also works to resolve how early life stage thyroid hormone disruption impacts brain development and function in zebrafish.

 

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