Bowel feeling | Medicine School


For more than a year, an unwelcome guest endangered Amanda Kabage’s life. Debilitating gastrointestinal symptoms – abdominal pain, blood in his stool and going back and forth to the toilet – happened so frequently that leaving the house has become almost impossible for the 32-year-old at the time. The culprit: recurring Clostridium difficile, Where C. diff, a bacterial infection of the intestine.

C. diff is a common complication of exposure to antibiotics. Ironically, the standard treatment for the infection is also antibiotics. Often the treatment works, but about 20% of the time it fails. In these cases, each treatment cycle makes the C. diff infection more difficult to eradicate. Each year in the United States, approximately 100,000 people are trapped in a cycle of C. diff infections. Kabage was one of them.

She read online about a promising new treatment for patients like her: a gut microbiota transplant. The procedure involves taking bacteria from the gut from a healthy person and introducing them into the intestinal tract of a sick person.

At the time, only a few doctors in the United States had Food and Drug Administration approval to perform microbiota transplants. Luckily, one of them – gastroenterologist Alexander Khoruts, MD – worked at the same location as Kabage: the University of Minnesota.

Khoruts, medical director of the U’s Microbiota Therapeutics Program and professor in the division of gastroenterology, hepatology and nutrition at the medical school, met with Kabage and agreed that a transplant might work. Khoruts scheduled the procedure, and after months of misery, Kabage finally had reason to hope.

Just hours after his transplant, Kabage felt an unknown energy bubbling up in his stomach, growls rumbling to a crescendo loud enough for his friend across the room to hear. Kabage knew immediately that the sound was coming from transplanted gut microbes moving into their new home.

“There’s just this physical, instinctive feeling that something different is going on,” she recalls. “The new germs are here and they will work.

Kabage was right: the transplant worked. Her chronic diarrhea stopped almost immediatelyLately, she has started eating solid foods again and has returned to training at the gym, running and playing racquetball.

“My life had come to an abrupt end,” says Kabage. “And then everything came back, my life completely normal, in just a few weeks.”

Amanda Kabage struggled with a C. diff infection for over a year. Today, she is a research coordinator and works with the team that cured her. (Photo: Scott Streble)

Understanding the microbiome

By the time he met Kabage in 2013, Khoruts was almost five years old in his exploration of the microbiome – the collective term for the trillions bacteria, fungi and viruses that live in each person, mainly in the large intestine.

Scientists knew that these microscopic creatures helped perform important tasks in the body, including digesting food, regulating the immune system, and producing nutrients. But the mechanics of their operation remained a mystery.

Khoruts has learned that the microbiome functions much like a city, with different, coexisting individuals working together as communities. When these communities are diverse and their interactions are numerous, the human host of microbes tends to be healthier. And when they are not, the person usually suffers.

Khoruts began to focus his research on the gut microbiome in 2008, after performing his first microbiota transplant. As in the case of Kabage, C. diff had derailed the entire life of the 61-year-old patient. Working with Michael Sadowsky, Ph.D., a microbial ecologist at U, Khoruts discovered an alarming lack of normal microbes in a woman’s gut. He asked the patient’s husband for a stool donation, which was used to create a microbiota transplant and administered via colonoscopy.

“She said she felt better while still in the recovery room. Soon we found out that her husband’s bacteria had taken over, ”Khoruts says. The demonstration of microbial transplantation was revolutionary, proving for the first time that microbes from a donor could survive and thrive in the recipient’s gut. “That’s when I realized it could help a lot of people.”

Soon after, the microbiota therapy program was born and Khoruts set to work to refine his transplant capabilities. He created the world’s first microbiota donor program, which recruits healthy individuals to donate stool samples that can be turned into microbiota transplants – the same type Kabage and over 700 others. C. diff patients have been admitted to the U since 2008. The methods published by Khoruts and Sadowsky after the first transplant have been adopted by groups around the world and have since treated nearly 100,000 patients with C. diff.

As the microbiota therapy program continued to grow, Khoruts realized that the donor initiative required the attention of a full-time research coordinator. He wanted someone who had detailed knowledge of the microbiota transplant process and had experience navigating the complicated rules and regulations of health-related research.

Kabage – who was working at U as a pediatric health research coordinator at the time of her C. diff diagnosis – was a fortunately perfect choice.

“Alex thought, ‘What are the chances that one of my patients is a researcher at the university who has become very passionate about this therapy? »», Explains Kabage.

From colonoscopy to capsules

Portrait of Alexander Khoruts

Hand holding pills / drugs

Alexander Khoruts, MD, and his colleagues can now deliver a microbiota transplant via capsules rather than colonoscopy. (Photo / s: Scott Streble)

Since taking office about six years ago, Kabage says the donor program has become a “well-oiled machine”.

Interested donors are subjected to a comprehensive medical history questionnaire and repeated in-person examinations that include blood and stool tests for infections and other health measures. Common disqualifications include food allergies, a history of asthma, and use of prescription drugs.

“They are literally the healthiest people we can find,” says Kabage.

Those who do the cup give stool samples several times a week and have ongoing in-person exams once every three months. Kabage and his team carefully study the samples before handing them over to a group dedicated to the U’s molecular and cell therapy facility that turns the samples into material for a transplant.

The Kabage transplant was administered by colonoscopy. But Khoruts wanted a way to make treatment more accessible, less intimidating, and significantly less invasive. So he and Sadowsky worked to create a capsule delivery form of gut microbes.

Today, most patients simply swallow capsules to receive their new microbiota. “They are surprised and relieved that that is all they have to do,” says Kabage.

In addition to managing the donor program and overseeing the logistics of the Microbiota Therapeutics Program clinical trials, Kabage also takes the time to speak with people who might benefit from a transplant – people whose experiences often mirror his own.

Have gastrointestinal illness such as C. diff is an isolated experience, she says. People are embarrassed to talk about what they are going through and are afraid of what others will think.

“It’s more than just ‘Oh, so you have diarrhea,’” Kabage says. “It minimizes a really debilitating disease. I’m happy to sit down with people and say, “I’ve been through this; here is my story. They will surprise themselves at how easy it is to talk to a stranger about what they are going through. And then they are also interested in our research.

Powerful potential

Most patients simply swallow capsules to receive their new microbiota.

As scientists learn more about the microbiome and its role in human health, Khoruts expects doctors to use microbiota transplants more frequently to treat a growing group of health problems.

Already, his team is collaborating with colleagues at U and across the country examining the link between the microbiome and disparate diseases, including inflammatory bowel disease, cancer, obesity, Parkinson’s disease and more. autism. While the specifics of each study are different, the central question is similar: Can restoring or stimulating the microbiome to a more optimal state create beneficial effects throughout the body?

To answer this question, Kabage and Khoruts are helping researchers design their clinical trials and providing them with microbiota transplant capsules created specifically for their studies. They also share the years of data they’ve collected from healthy donors and patients.

Members of the Masonic Cancer Center Armin Rashidi, MD, Ph.D., and Shernan Holtan, MD, too of the division of hematology, oncology and transplantation of the faculty of medicine, working with Khoruts and his team to determine whether microbiota transplants could help patients recover from the difficult sequelae of cancer treatment, including graft-versus-host disease, which kills nearly 10% of leukemia patients and who are undergoing blood and marrow transplants.

“We believe that giving our patients a microbiota transplant before their leukemia treatment could help them recover and avoid graft versus host disease,” said Holtan. “Or maybe for people who already have it, a transplant could give them the ammunition they need to survive.”

To expand future collaborations, says Khoruts, the next step may be to evolve the microbiota therapy program into a multidisciplinary center that facilitates all microbiome research in the United States. It envisions a centralized hub where interested researchers from any field can collaborate on projects, explore and share data and findings, and continue to shed light on the role of the microbiome in human health.

You need a lot of researchers using the same protocols and pooling their data because the microbiome is so complex. There is a lot to learn.

– Alexander Khoruts, MD

“It’s a whole new era of therapy,” he says. “But the nature of this science is such that it only works when it is big. You need a lot of researchers using the same protocols and pooling their data because the microbiome is so complex. There is a lot to learn.

Besides reducing inefficiencies in the research process and streamlining data collection, the center’s ultimate goal would be to develop new breakthroughs related to the microbiome. Which, as Kabage knows, can be life changing.

“I am eternally indebted to the work of Dr Khoruts,” she said. “It changed my life as a patient and inspired my career as a researcher. Being part of the team helping other people who may benefit from this amazing treatment, I don’t prefer anywhere else.


Comments are closed.