December 2, 2022

The future will be personalized: Accelerating microbiome research

By Susan Murphy
Purna Kashyap, M.B.B.S. (right), and Nicholas Chia, Ph.D. (left), are co-associate directors of the Microbiome Program in the Mayo Clinic Center for Individualized Medicine.

By Mayo Clinic Alumni Magazine contributor

We’re in the midst of a microbiome research epidemic, according to Purna Kashyap, M.B.B.S., co-associate director of the Microbiome Program in the Mayo Clinic Center for Individualized Medicine. “We started early and are pushing hard,” says Dr. Kashyap. “We’re one of the top accelerators in the field and are well poised to move microbiome research findings to the clinic. We anticipate that happening in another decade or so.” Dr. Kashyap is a professor in the Mayo Clinic College of Medicine and Science.

Microbiome-related research at Mayo Clinic focuses on improving patient outcomes or bringing microbiome discoveries to clinical practice — an area in which Mayo Clinic leads. The Microbiome Program provides resources for Mayo Clinic researchers doing this work, providing knowledge and infrastructure assistance.

“Microbiome research is young, vibrant and ongoing,” says Dr. Kashyap. “We don’t have all the answers yet, but we know the microbiome is a component of multiple chronic diseases and an important contributor if not always the inciting factor.”

Dr. Kashyap’s Microbiome Program co-associate director, Nicholas Chia, Ph.D., concurs: “There is mounting evidence that changes in the microbiome may be implicated in the development, progression and treatment of multiple diseases. Eliminating dangerous microorganisms or restoring normal microbiota may reverse this process. This is a critical possibility that we are still learning more about.” Dr. Chia is an assistant professor in the Mayo Clinic College of Medicine and Science.

Microbiome research at Mayo Clinic includes studying the role of bacteria, fungi and viruses in disease states ranging from cancer to obesity and everything in between. A large trial of cancer patients is analyzing whether the microbiome can be used as a biomarker to predict cancer treatment response and adverse events. In another project, Mayo Clinic has licensed a bacteria to a biotechnology company for further study about its role in suppressing multiple sclerosis and rheumatoid arthritis. Another project Mayo collaborated on resulted in a commercial product to provide microbiome-directed personalized nutrition to regulate blood glucose and prevent complications of diabetes and prediabetes.

Dr. Kashyap compares microbiome research to genome research. “The human genome was sequenced in 1991. In 2022, we use it to predict risk and tailor disease treatment. That was one genome. Microbiome complexity is much higher, and we’re trying to do the same thing in terms of sequencing and understanding. We’re making progress and, while we stumble along the way, we have learned from early failures that which has positioned us well for future success. One way in which the microbiome is particularly exciting is that it is modifiable whereas genes are not.”

He predicts that the first FDA-approved microbiome-related therapies will be stool substitutes to reset the microbiome of the colon in patients who have Clostridioides difficile (C. diff) infection.

“In the future, we’ll be able to look at a person’s microbiome and tell a patient their risk of developing a disease, much like we do now with commercially available human gene panels. This holds promise as a preventive strategy because, unlike our genes, the microbiome can be changed. What we already see across the horizon in diseases such as cancer and autoimmune conditions is the ability of an individual’s microbiome to predict which treatments will be effective or have the fewest side effects and how a person might respond to different treatments so we can eliminate trial and error and start with the best treatment first. We also could try to change the microbiome with diet or prebiotics to improve chances of success with a treatment. But we’re not there yet. We’re moving at a fast rate, and I’m optimistic that we will have early wins by the end of this decade.”

In the meantime, Dr. Kashyap advises people interested in keeping their microbiome healthy to eat a high-fiber diet from diverse food sources. “Most chronic diseases have microbiomes that show low diversity. We know that a highly diverse state is more resilient to change, and a high fiber diet will increase the diversity of your microbiome.”

Moving the needle in GI motility

Dr. Kashyap’s own research focuses on the role of the microbiome in disorders of the gut–brain interaction and how bacteria affect the functions of the intestine, such as motility, which can be altered in these conditions. His lab found that bacteria can convert tryptophan to tryptamine, which is similar to serotonin produced in the gut. Researchers in the lab found that tryptamine activates a receptor in a mouse gut that normally responds to serotonin and increases secretions in the intestine, resulting in faster movement of food. They engineered a bacteria to produce high levels of tryptamine in the intestine as a designer probiotic that could benefit patients who have constipation. This needs to be tested in humans.

“Bacterially produced tryptamine quickly degrades in the intestine and doesn’t appear to increase in the bloodstream,” says Dr. Kashyap. “Our goal is to find treatments that act only in the GI tract without creating problems in other parts of the body.”

Dr. Kashyap’s lab also is studying C. diff infection and how this bacteria manages to remain in the intestine, causing disease again and again. Dr. Kashyap is exploring the possibility that C. diff sticks to the intestine by forming a biofilm on its surface and evades antibiotic treat ment. His long-term goal is to develop new biomarkers and microbiota-targeted therapies to treat GI disorders.

“The next generation of probiotics may involve engineering bacteria to change the microbiome or influence its function, whether that’s producing large amounts of tryptamine or other molecules that affect GI function,” says Dr. Kashyap.

This article was originally published in Alumni Magazine, 2022, issue 3.

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Tags: Dr. Nicholas Chia, Dr. Purna Kashyap, genomic medicine, Microbiome, Multi-omics, Precision Medicine, Research

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