Minnesota researchers help unlock 'gut science' cures

The Twin Cities is emerging as a major player in what could become a multibillion dollar industry: Gut science.

Minnesota's rich expertise in fields as different as soil science, genomics and experimental medicine has enabled researchers here to become pioneers in a new field of medicine that aims to harness the healing power of the microbes that live in everyone's belly.

The technique — known as "fecal microbiota transplantation" — is driving a fast-evolving branch of molecular medicine. Researchers believe that a large number of health conditions may be linked to the microbes that are present — or missing — from a person's intestines. Minnesota scientists have modernized ways to analyze how a healthy person's gut microbes can be transplanted into a sick person to cure deadly infections with surprising reliability.

In the future, pediatricians "are going to examine babies — and babies' diapers," microbiologist Dr. Martin Blaser of NYU Langone Health told a gathering of students in a recent talk at the University of Minnesota. "They're going to ask, does this baby have all the microbes that a normal baby should have? ... And if they don't, they're going to reach into their shelf, and ... give those microbes back. This will become a part of the medicine of the future."

Changes in the "microbiome" of bacteria in the intestines can have profound impacts on health.

The trillions of microscopic gut microbes in a person's body act with their immune system to protect against various deadly pathogens. The gut microbiome also helps extract energy and nutrients from food.

Private companies, not-for-profits and gastroenterologists around the nation have begun using the techniques invented or honed in Minnesota to exploit the microscopic contents of a person's gut.

One of the leading players is Rebiotix Inc. of Roseville. The company is in the final phase of human testing of a gut microbiome treatment for the deadly infection Clostridium difficile (C. diff) that could be the first such treatment approved by the Food and Drug Administration.

Another growing company in the space is CoreBiome of St. Paul, which was spun out of the University of Minnesota Genomics Center to provide microbiome analysis.

Meanwhile, health care providers at the U and the Mayo Clinic offer microbiome treatments for recurrent C. diff infection under a special FDA waiver. (The treatments are experimental and therefore often not covered by insurance.) Industry experts expect to see more clinical trials looking at a diverse range of issues, from inflammatory bowel disease and colitis to autism and depression.

"The big picture idea is, can we look at the microbiome of individuals in the future and say, 'This microbiome pattern we recognize as leading to X type of disease,' and then treat the microbiome before that person develops disease, kind of like high blood pressure," said Lee Jones, who left a role as CEO of the University of Minnesota's Venture Center shortly before co-founding Rebiotix in 2011.

For now, the Rebiotix microbiome treatments for C. diff are among the closest to achieving FDA approval. Last week, the health care publication Stat News reported that the influential Infectious Diseases Society of America has issued its first-ever guidelines that recommend the use of fecal microbiota transplants for recurrent C. diff infections.

The first-line treatment for C. diff infections is to give powerful antibiotics, even though antibiotics actually kill off the natural gut bacteria that fight C. diff, creating a vicious cycle on infections. The Centers for Disease Control and Prevention says C. diff caused 29,000 deaths in 2011 — far more than infectious diseases like HIV, for example.

Using one person's feces to treat another person's gut infection is not a new idea. Chinese practitioners reportedly used the technique some 1,700 years ago, and western doctors were reporting cases in the literature starting in the 1950s. Doctors in Duluth had been performing versions of the procedure.

In 2008, the University of Minnesota's Dr. Alex Khoruts successfully treated a 64-year-old woman who'd had C. diff infection for eight months. Khoruts knew of the fecal transplant reports in the literature, but he said the methods were crude, involving breaking down donor feces in a kitchen blender.

Khoruts treated 10 cases using those methods, and the drawbacks were tough to miss: "The olfactory potency of human fecal material revealed at the touch of a button on the blender can be quite shocking — it can empty the waiting rooms," he said in a 2014 article in Global Advances in Health and Medicine.

The multidisciplinary Microbiota Therapeutics Program that was assembled to support fecal microbiota transplants (FMTs) at the University of Minnesota quickly began to modernize procedures for gathering, purifying and analyzing samples.

The program set up a standardized fecal donation process, in which potential donors get thorough health screenings. Once the donation is collected and screened, it is processed in an FDA-regulated facility so that only the living microbes remain. These are then freeze-dried and frozen.

"At the time, the idea of standardizing the donor process and banking the material shifted the paradigm," Khoruts said. "It was considered seminal work at the time. In retrospect, it's like, duh."

Khoruts and his team also used modern rapid genetic sequencing technology to test the hypothesis that one person's gut microbes can be truly transplanted into another person. No one had done that until Khoruts left his Minneapolis office and walked into the office of environmental microbiologist Michael Sadowsky on the U's St. Paul campus.

Sadowsky's team in the Department of Soil, Water and Climate studies microbes in rivers and soil, which tend to contain between 5,000 and 20,000 microbial species per gram of material.

"The gut has only between 700 and 1,000 species. So while that might sound like a lot, it is much less complex than soil is," Sadowsky said. "The exact same technology is used regardless of the environment you are looking at, whether it is soil, whether it is water, or the gut."

The researchers found that the devastated intestines of C. diff patients were fertile ground for donor microbes. More than 450 procedures have been done there so far.

Now, the donor microbes can be given in capsule form. A June 2017 paper in the American Journal of Gastroenterology noted 49 people who were treated this way at the University of Minnesota, with promising results: After two months, 88 percent had no recurrence of symptoms. Rebiotix is also studying its own encapsulated microbiota therapy.

Still, the field has hurdles to overcome. Patients and physicians may resist therapies derived from human feces. Failure can be expensive: Investors lost big when a clinical trial by Seres Therapeutics of Boston failed to live up to expectations in 2016, for instance.

The field also remains obscure, though that may be changing. Rebiotix's Jones now serves on the board of the local trade group Medical Alley Association, joining executives from Medtronic, Boston Scientific, 3M and the like. Overall awareness of microbiome therapies is growing. Such changes could be good for the Twin Cities.

"It's a field that hasn't had the attention that lots of others have," Medical Alley CEO Shaye Mandle said. "People are focused on cancer and diabetes, issues that grab the headlines. But this is a tremendous area of opportunity."

Joe Carlson • 612-673-4779