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by Stephanie Folk

Organ transplants can offer patients with debilitating and deadly diseases a chance at a longer life and improved health.

But the new organs come with strings attached. Patients take on a life-long regimen of antirejection drugs, some with serious side effects, as we pointed out in a recent post.

Maria-Luisa Alegre, MD, PhD, is working to help transplant patients stay healthier longer, with fewer drugs. She is uncovering some surprising ways that diet, exercise, and microbes influence the immune system’s response to a transplant.

The immune system often attacks a new organ in much the same way it would defend against a viral or bacterial infection—a recipe for organ failure. To prevent transplant rejection, patients must take drugs to suppress the immune system, but there are consequences.

“People become more susceptible to infections and cancers when the whole immune system is suppressed,” says Alegre.

Scientists are exploring multiple strategies to improve outcomes. Alegre’s colleague Anita Chong is developing treatments designed to target only mechanisms of the immune system that react to the transplant, while maintaining its ability to fight disease. Other researchers are working to bolster tolerance, essentially retraining the immune system to treat the new organ as harmless.

Alegre and her team are approaching the challenge from yet another angle.

“In recent years my lab has become interested in the environmental factors that may influence immune response against the graft. What about dietary interventions? Things like exercise? More recently, we’ve been wondering about the microbiota.”

These are the army of microbes that colonize the body. While we often think of microbes as contributors to disease, most are actually important to health, aiding in the digestion, producing nutrients, tuning the immune system, and possibly even boosting the body’s ability to fight cancer. Alegre is using germ-free mice to test the impact of different types of microbes on transplant rejection.

“From this work we know, indeed, the microbiota influences rejection, and we have found some microbial communities that augment the immune response against a graft. But we have also found some microbial communities that can suppress the immune response.”

Alegre and colleagues are cultivating the bacteria that appear to slow down rejection to see whether they might work as a sort of probiotic therapy. They are also investigating the microbes that increase the speed of rejection in order to determine whether selectively eliminating these bugs could reverse the process.

Alegre notes that microbial influences could also help to explain why organs like lungs and intestines, which are exposed to the outside world and colonized by microbes, are typically rejected faster than organs like kidneys, which are sterile. She is exploring whether changing the microbes in a donated colonized organ like a lung could make it more like a kidney, a sterile organ, in terms of transplant tolerance.

Alegre’s studies in mice have shown that a high fat diet can also accelerate rejection of a graft, while exercise seems to slow rejection. Though the mechanism is not yet clear, the results suggest that a shot at a longer functioning transplant may be one more of the many benefits that come from staying active and eating a healthy diet.

While transplant success is a multivariable equation, Alegre’s work points out factors to improve the organ’s chances. Medical discovery takes not just a village but a giant community. By pooling their knowledge—sometimes over decades—scientists are creating a clearer picture of the complex workings of the immune system and how it responds to transplants. Their research could lead to better antirejection therapies that help patients live better, with fewer drugs.

No strings attached.

Stephanie Folk is a senior assistant director of development communications for the University of Chicago Medicine & Biological Sciences Development office.