The latest findings from principal investigator Dr. Thomas Sharpton reveal how a common pollutant can alter the gut microbiome and shape behavior across multiple generations — advancing the science of healthy aging.
New research from the Linus Pauling Institute is revealing how environmental exposures can influence health across the lifespan and even across generations. In a recent study, principal investigator Dr. Thomas Sharpton, in collaboration with Dr. Robyn Tanguay, showed that, in zebrafish, early-life exposure to a common pollutant can alter the gut microbiome, change behavior, and produce effects in future generations of offspring who were never directly exposed.
This work advances a growing understanding that the gut microbiome is a key factor in chronic disease risk, resilience to stressors, and healthy aging. By uncovering how pollutants interact with gut microbial communities through signaling pathways involving the aryl hydrocarbon receptor (AhR), which is involved in development, immunity, and metabolism of foreign compounds, Sharpton’s research highlights new opportunities for earlier detection and disease prevention.
As part of the Institute’s mission to extend healthspan, these insights help explain how environment and gut microbial ecosystems interact and shape our well-being. Below, Sharpton discusses his recent findings and their implications for future preventive health research.
Interview with Dr. Thomas Sharpton
What do you study?
We are principally interested in understanding how differences in the gut microbiome explain much of the variation that we see in health and physiology across human populations.
We hypothesize that one reason we see such a sharp rise in chronic diseases is because recent lifestyle and environmental changes have disrupted the types of microorganisms we harbor inside our gastrointestinal tracts. Historically, biomedical research has missed this major piece of the puzzle: the gut microbiome; without it, our understanding of health and physiology is incomplete.
With the development of new technologies, there is now tremendous opportunity to transform how we prevent, manage, and treat disease. There are many important variables to consider, including this previously overlooked variable: how managing and maintaining our gut microbiome can help us manage and maintain our own health over the long run.
Insight Spotlight:
Why the Microbiome Matters for Healthy Aging
- The gut microbiome influences immunity, metabolism, and the nervous system.
- Exploring disruptions in gut microbial communities may be an avenue to address chronic disease.
- Early-life exposures can shape gut microbial patterns for decades and potentially across generations.
- Researchers are uncovering the biological mechanisms that connect environment, diet, and gut microbiome composition to long-term health outcomes.
What motivated this study on pollutants and microbes?
Industrialization has exposed us to a tremendous diversity and abundance of environmentally ubiquitous pollutants. Whether we like it or not, we often consume these pollutants in our food, drinking water, and the air we breathe.
One of the most well-studied pollutants in the history of toxicology is benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) and well-recognized carcinogen. Emerging work suggests BaP is also a neurotoxin, meaning exposure can negatively affect the brain, nervous system, and behavior.
Why focus on benzo[a]pyrene?
PAHs like BaP are byproducts of burning organic material. Some of the main sources include automobile exhaust, cigarette smoke, wildfire smoke, and charbroiled and smoked foods. BaP is widely present in our day-to-day environment, making it an important compound to study when trying to understand environmental impacts on health and long-term biological outcomes.
Why use zebrafish as your model?
Our interest is in human health, but it is difficult to chase certain types of questions in human populations. Model organisms like zebrafish allow us to build a foundation of knowledge that informs investigations in more complex systems.
Zebrafish are a powerful model in toxicology research because they share important genetic and physiological traits with mammals, are sensitive to environmental pollutants, and allow us to use a wide array of experimental techniques on large numbers of individuals.
We started this investigation in zebrafish with the goal of returning to our initial hypothesis: has industrialization changed our environment in a way that affects our gut microbiota’s contribution to health?
What did you discover?
In short, we found that continuous exposure to BaP during embryonic development:
- Altered the composition of the gut microbiome in adult fish
- Changed behavior in adult fish (specifically anxiety and social behaviors)
- Produced transgenerational effects, meaning later generations who were never exposed to BaP still showed consequences of their parents’ and grandparents’ exposure
- Required genetic factors, such as the presence of the aryl hydrocarbon receptor (AhR), for these changes to occur
What role does the AhR receptor play?
The AhR is a receptor that recognizes PAHs like BaP, certain phytochemicals, and compounds produced by gut microbes. Once this receptor binds to one of these compounds, it interacts with host cell DNA, causing changes in gene expression and cellular function. It’s a major avenue of communication between gut microbes and our physiology.
In our experiments, we observed that interfering with AhR genes changed how the gut microbiota of zebrafish responded to BaP — and that response subsequently affected the behavior of zebrafish adults.
What could this mean for preventing chronic disease and improving healthspan?
We don’t yet fully understand the mechanisms, but we think BaP exposure alters the types of microbes that live in the fish gut, which then affects behavior. We also think BaP exposure affects the genome of the embryo in a way that influences future generations, shaping the kinds of microbes they recruit.
It is a very complex, interconnected relationship. There is enormous potential for this research to transform medicine, but much remains to be resolved. Understanding these interactions could lead to new diagnostics, treatments, and prevention strategies for chronic diseases.
What’s next?
One direction is to move into mammalian models, such as mice, to determine whether the same processes operate and whether the microbiota plays a causal role. We already have ongoing human studies looking at related questions.
Another direction is to conduct the same types of zebrafish experiments with other pollutants. We may be able to observe changes in the gut microbiota before there are obvious signs of disease, which could transform how we define exposure safety thresholds.
Sharpton’s findings strengthen LPI’s leadership in uncovering how environment, diet, and the microbiome shape lifelong health. By revealing pathways that link early exposures to long-term and even multi-generational outcomes, this work advances the Institute’s mission to extend healthspan and fuels new possibilities for earlier disease detection and smarter prevention.