Every part of your life, from your birth to the places you’ve lived to the snack you just devoured, shapes the community of microbes living in your intestines. This diverse population of bacteria, called the gut microbiome, feeds on the nutrients and chemicals in what you eat and drink. It shifts and transforms in response to each meal.

Over time, changes in your gut microbiome can significantly impact your health: A well-balanced gut microbiome can benefit mental and physical health, but imbalances in gut microbial communities are associated with a wide array of diseases, including irritable bowel syndrome, cancer, and neurodegenerative disorders. Snehal Chaudhari, an assistant professor in the Department of Biochemistry, wants to know exactly why and how the gut microbiome has such an oversized impact on the onset and progression of disease.

Working with researchers in the UW School of Medicine and Public Health and industry partners, Chaudhari is investigating the compounds that gut-dwelling microbes produce. Her research will help develop ways to support human health — and keep our gut microbiomes thriving.

What interests you about the gut microbiome?
People say you are what you eat. I think you are what the microbiome does to the food you eat. Some studies reveal associations between the gut microbiome and disease. But how the microbiome affects the onset and progression of disease — that’s what we still don’t understand.

Of the hundreds of bacterial strains making up the trillions of bacteria in our gut microbiome, which ones account for differences in human health? Knowing more about the mechanisms of how the gut microbiome influences diseases can help us to develop precision medicine that is geared towards a specific person’s microbiome.

What impacts the gut microbiome throughout someone’s life?
There are many ways that the gut microbiome evolves over the course of a lifetime.

One is what you’re born with and what you acquire during infancy. Whether a baby is born vaginally or via Cesarean, whether a baby eats breast milk or formula — these transcend genetics and play big roles in which microbes the gut is initially exposed to.

Another is medication, especially antibiotics used during childhood. Antibiotics save lives by killing pathogenic bacteria, but they also kill beneficial bacteria in the gut. Even one dose of antibiotics can have lasting impacts on the gut microbiome.

A third is diet. Our microbiota are exposed directly to the things we consume, which change and shape our gut microbiome over time.

What are some areas of focus in microbiome research?
Studies over the past couple of decades have explored associations between the gut microbiome and diseases. There are some microbes, for example, that are associated with health in some cases and a type of cancer in other cases. Researchers are starting to tease apart this counterintuitive information by looking at individual bacterial strains and bacterial communities to discover the biochemical products they generate in our intestine. Additional factors such as race, ethnicity, and geographical location also play a role. Further, we’re now getting down to the molecular level to look at specific strains, on a case-by-case basis, to determine whether they can cause or combat disease — and how.

How does your work fit into this research landscape?
My lab studies folates, or vitamin B9, and how they influence diseases. Of the hundreds of strains of bacteria inhabiting the human gut, some can make folate, which is essential for our growth and survival.

But our bodies can’t make folate, so we depend on our diet and gut bacteria for our folate. We’ve found that bacterial folates can influence liver disease and cancer. Some folate molecules can influence gut inflammation; and, we recently learned, some can also affect neurological disorders. What we don’t yet know are the underlying mechanisms: how folate levels or specific folate molecules affect the host or the gut microbiome, what the gut microbiome is doing to these dietary compounds, and how that affects onset or progression of disease.

My lab has developed research tools to investigate bacterial communities and the molecules they produce to identify their function in disease, a foundational understanding that can lead to future cures. I collaborate with researchers in the medical school, including Rich Halberg, who is a colon cancer expert, Dudley Lamming, who is a neurodegenerative disease expert, and Dave Harris, who is a bariatric surgeon. They each have unique mouse models that can help us study how the gut microbiome shifts in disease and how factors produced by different bacterial communities affect onset and progression of disease.

It seems that research about the gut microbiome intersects with areas of interest across campus. Do you have other partnerships that are helping to advance this work?
We’re working with WARF [Wisconsin Alumni Research Foundation] on anti-diabetic and anti-gut inflammation therapeutic treatments. We screen our library of unique compounds that gut bacteria produce to identify which ones trigger cellular pathways that are relevant for disease and to understand the under-lying mechanisms. WARF researchers mine large compound databases to test how modeled effects of compounds can be more effective at triggering these cellular pathways. Then my lab uses our tools to test the new compounds to find the most potent therapeutic.

We also partner with the company Pfizer Inc. on similar work related to fatty liver disease. This metabolic disease affects nearly a third of the U.S. population and is difficult to diagnose early. We are interested in finding biological markers that indicate whether someone is more likely to develop the disease to help with early diagnosis. If diagnosed early enough, the resulting liver damage can be reversed with simple lifestyle and dietary changes.

How do you see your work fitting into the broader CALS research community?
Agricultural research helps to make food more nutritious and more available. My work investigates how food affects the gut microbiome and, in turn, our health. The goal is to help identify therapeutic measures and develop a personalized approach to health that balances and supports the gut microbiome. CALS also has a long and storied history in vitamin research, leading to some of the biggest breakthroughs in this field. There is a direct connection between your diet, your gut microbiome, and your mental and physical well-being. Small molecules such as folates bridge this connection, and CALS is perhaps the best place in the world to do research in bacterial folate metabolism and biochemistry.

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Research in Snehal Chaudhari’s lab is supported by funding from the National Institutes of Health.

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This article was posted in Basic Science, Health and Wellness, Living Science, Spring 2025 and tagged Biochemistry, disease, folates, gut microbiome, UW School of Medicine and Public Health, vitamins, Wisconsin Alumni Research Foundation (WARF).