The gut microbiome offers a unique snapshot of each individual, shaped by genetics, environmental exposures, lifestyle habits, and the body’s own physiology.
“If you take two different individuals, it’s highly improbable that their microbiomes are going to be exactly the same,” said Purna C. Kashyap, MBBS, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota. Although the specific mix of bacteria, fungi, and other microorganisms varies widely, their functional roles often overlap, making it challenging to define a universally “healthy” microbiome.
Kashyap’s career has centered on finding critical associations between gut health and chronic gastrointestinal diseases. In an interview with Medscape Medical News, he discussed his work developing targeted therapies and biomarkers for disorders of the gut-brain axis, focusing on the interaction between gut bacteria and dietary components, particularly carbohydrates, which are a significant nutrient source for gut microbes.
You’ve described the gut microbiome as being as unique as a person’s fingerprint. What does that mean in practical terms?
Each individual harbors a unique set of microbes, which is driven by their individual health. That does not automatically imply that what the microbes are doing in the gut is different among every individual. Different bacteria can perform the exact same function.
That’s why defining what’s a “healthy” microbiome or microbiota is so difficult. There’s not a single set of bacteria that are healthy. There are a lot of different combinations of bacteria that could be seen in healthy individuals, which all perform the same function.
What are the main factors that affect a person’s microbiome over time?
Genetics play some role in which microbes are present. As we are born and acquire microbes, we develop tolerance to them. Over time, you tend to accumulate a set of microbes that become stable and form your microbial community.
Environmental exposures also dictate what kind of microbes are present, as will dietary habits. People living in California are going to be exposed to very different microbes compared with those living in Minnesota or New York.
Medications can change microbes in multiple different ways. Microbes by themselves may have genes that break down medications, and as a result, taking a specific medication can enrich those bacteria. Medications might change the environment within the gut, which can dictate what kind of microbes are present. Antibiotics are meant to treat an infection in some other part of your body, and the bacteria in your gut are the collateral damage. Fortunately, gut bacteria are not as fragile as we think. As long as you have a robust gut microbial community, it tends to spring back to its original state within 3-4 weeks.
Bowel habits can also dictate what kind of microbes are present. While bacteria can affect your bowel habits, conditions like constipation and diarrhea can also change the gut microbial composition, making it a chicken-and-egg problem.
Can probiotics help strengthen or restore the microbiome?
The challenge is that probiotics are regulated under very different rules and there are no clinical studies for most of the probiotics on the market. We looked at this as a part of the American Gastroenterological Association guideline, focusing only on randomized controlled clinical trials, and did not find probiotics to have a benefit in the majority of the adult gastrointestinal disorders.
Much of our research focuses on the interaction between gut bacteria and dietary carbohydrates. Why are carbohydrates so important to study?
Simple sugar carbohydrates get broken down and absorbed in your small intestine just like proteins. In contrast, complex carbohydrates, like those in fiber-rich foods, have nondigestible parts our body hasn’t learned to break down. That is what reaches the colon, where microbes use this to produce fermentative end products.
The most common ones we study are short-term fatty acids, which are important fuel for the lining of our colon and help maintain the integrity of this colon lining, both in terms of supporting the cells and the barrier between these cells.
That’s part of why a lot of the focus has been on carbohydrates because they’re a big source of nutrition for the microbes in our gut.
What are the main goals of your research into the gut-brain axis?
My clinical practice is focused on disorders of the gut-brain axis, where patients often have changes in gastrointestinal motility and sensation. A major part of that is trying to figure out how gut bacteria affect gut transit (how things move through the gut), as well as how we sense pain in the gastrointestinal tract.
My lab studies how bacterial metabolites determine these physiologic functions of the gut. Diet adds a layer of complexity because bacteria produce metabolites by interacting with what we eat.
Patients with irritable bowel syndrome or similar disorders of the gut-brain axis have alterations in their transit time. They either have constipation, diarrhea, or both, along with abdominal pain. We want to use bacterial products or bacteria that produce specific molecules to target transit and pain sensation.
Bacteria can only produce molecules from what they get as nutrients, and that comes from your diet. For example, butyrate is an important bacterial end product, but if your diet is very low in dietary fiber, then your bacteria cannot produce enough of it. Low butyrate levels have been associated with different diseases.
Once we identify these molecules, the goal is to find the bacteria that produce these metabolites, which can affect transit or sensation in the gut, and then use them as therapeutic bacteria to help restore some of those functions.
Current probiotics are not as useful because they were developed from what we consider to be beneficial bacteria, rather than mechanistic studies looking at what bacteria are relevant to a disease state in terms of modulating an individual’s physiology. Once we start moving to that level of probiotic interventions, I think we’ll see much more successful interventions rather than just using a group of bacteria associated with health.
How might microbiome imbalances contribute to chronic diseases beyond the gut?
Chronic diseases are not the same as acute infections. Instead, they are often multifactorial, where the environment, microbiome, and genetics likely all contribute to the disease. The important question is how much the microbiome contributes to these chronic diseases in different individuals, and which bacterial metabolites or functions are responsible.
In Parkinson’s disease, for example, there’s a hypothesis that the initial inciting event is in the gut, which then drives changes in the brain. We don’t know what that exact pathway is yet.
What areas of microbiome research are you most interested in exploring next?
How microbes can interact with medications, especially in the cancer realm. Just as we have genes to break down medications, bacteria do as well. As a result, they can either make a medication more efficacious, less efficacious, or can drive side effects. We are trying to look at how microbes interact with these medications to change outcomes as well as adverse events.
While our focus is cancer, it’s going to be applicable for medications used in most chronic disorders.
Kashyap is a member of the scientific advisory board of the International Observatory of Biocodex Microbiota Institute, chair of the scientific advisory board of the American Gastroenterology Association Center for Gut Microbiome Education and Research, ad hoc advisory board member for Pendulum, and Intrinsic Medicine, and advisory board member for 32 Biosciences for which he receives equity option as compensation.
Jennifer Lubell is a freelance medical writer in the Washington Metropolitan Area.