Exploring gut bacteria’s role in disease and human health

Family having a meal

For as long as humans have been around, the normal function of their intestinal tract has relied on the complex interplay of trillions of microscopic organisms, which in turn thrived off of the food we ate. Now, through pressure from modern diets and medicines, that longstanding partnership may be falling out of balance.

Dr. Alexander Khoruts, medical director of the University of Minnesota Microbiota Therapeutics Program, highlighted at a recent lecture how some of the growing health challenges we face today could stem from the changing composition of the microbes in our intestines. Microbes constitute an integral part of the human body and interact with it in complex ways. Recent research suggests that the diversity of microbes in people is shrinking and this may be causing significant health problems in our population. “The Evolving Human Microbiome,” hosted by the U’s Consortium on Law and Values in Health, Environment and the Life Sciences on Feb. 17, explored the ramifications of our bodies’ changing microbial communities.

“We’re discovering that these microbes are important for our health and for disease,” Khoruts said. “For the most part, it has been a mutualist relationship — what’s good for them [the bacteria] is good for us. But these relationships can go wrong.”

How modern life hurts the microbiome

Why are our gut microbes having so much trouble? Khoruts highlighted three areas that could contribute to decreasing diversity among human microbes.

The first area relates to infancy. When a mother gives birth naturally, she transfers bacteria to the baby that serve as the building blocks for the baby’s microbiome. One important method of microbial transfer is the mode of delivery. C-section births fail to provide the right bacteria that jumpstart the baby’s own microbiome, as do other practices that limit bacterial transmission to the baby, such as bottle feeding and frequent or extensive bathing. Providing the right bacteria to the newborn is important because the microbes are involved in the development of the baby and hardwiring his or her immune system, body metabolism and neural circuitry.

Widespread overuse of antibiotics in medicine and agriculture is another factor. Antibiotics, while important in treating infectious diseases, also disrupt that normal microbial communities in their host. In fact, antibiotics break the fundamental contract humans have had with their microbial partners for millions of years. The result is emergence of drug resistant “superbugs” that cause ever more serious infections that are extremely difficult to treat. This is a growing problem that is one of the most urgent and disturbing developments in medicine, Khoruts said.

The third issue is highly processed food. The small intestine rapidly digests fast foods, refined grains and foods that are high in sugar or high-fructose corn syrup, which leaves little in the way of nutrients for the bacteria at the end of the digestive tract to eat. These starving bacteria, located in the colon, may be sending signals to the brain that tell a person to eat more. If that person then eats more of the same processed food and continues starving the hungry bacteria, it creates a vicious cycle that can result loss of important bacteria in the intestine, obesity and all its consequences, including diabetes.

Using gut bacteria to treat disease

Khoruts has an extensive experience studying how the microbiome affects human health. One aspect of his current research, funded through the MnDRIVE Transdisciplinary Research Program, brings together experts from across academic disciplines, including microbial ecology, nutrition, endocrinology, psychiatry and biochemistry, to try to better regulate blood sugar in people with diabetes. By implanting beneficial bacteria into the intestines of diabetes patients, Khoruts and his team aim to correct insulin sensitivity, which could treat not only diabetes, but other complications from metabolic syndrome, including obesity, high blood pressure and liver disease. Ultimately, the project will help inform the development of new, microbe-based therapies that can lead to better health.

For a number of years Khoruts has also been working with Mike Sadowsky, Ph.D., director of the BioTechnology Institute, to take on Clostridium difficile, one of the potentially deadly “superbugs” that releases toxins and damages the lining of the intestines. Normal gut microbial communities can keep C. difficile in check, but this protective function is lost when these microbial communities are disrupted, typically through antibiotic use. Khoruts and Sadowsky developed and standardized a microbiota transplant, which is now becoming incorporated into mainstream medicine. This treatment has proved successful in curing about 98 percent of patients that fail to benefit from all other standard therapies. The University’s Microbiota Therapeutics Program has treated approximately 400 patients suffering from refractory C. difficile infections and plans to expand its research and collaborations to tackle other challenges associated with the dysfunctional microbiome.

Learn more

Watch a recording of The Evolving Human Microbiome to hear Khoruts discuss his research, with commentary afterward from Dan Knights, Ph.D., assistant professor of computer science and engineering in the College of Science and Engineering who is also with the BioTechnology Institute.

There are two more lectures in the microbiome series: “Fecal Microbiota Transplantation: Ethical Challenges and Regulatory Hurdles” on March 8 and “Microbiota-targeted Therapies from Probiotics to Transplants: New Regulatory Challenges” on April 21. To learn more about these and other upcoming lecture opportunities, visit the Consortium events page.