In the U.S., almost 115,000 people are on the waiting list for a lifesaving organ transplant. Even for those that do receive a transplant, it doesn’t always go well. A transplant rejection can occur at any time.   

Those who finally receive a transplant may end up with a transplant rejection five to eight years after transplantation, which could occur for a multitude of reasons, including the quality of the organ, the health of the recipient, whether the donor was alive or deceased and even the donor’s age.

Now, in a first-of-its-kind study, scientists from the University at Maryland School of Medicine have revealed that the success or failure rate of a heart transplant may be influenced by a key factor: the gut microbiome. The link between the two is the immune system. Certain bacteria in the microbiome can trigger pro- or anti-inflammatory signals, and these signals can affect how the immune system responds to the transplanted organ.

Jonathon Bromberg, a professor of surgery, microbiology and immunology at University of Maryland School of Medicine, wanted to investigate the link between gut microbiome and the immune system in relation to long-term organ transplant rejection—any rejection that occurs between five and eight years.

Bromberg and his colleagues hypothesized that transplant outcomes are impacted by changes in the gut microbiota during organ transplantation, therapies and antibiotics.  The researchers tested their hypothesis in an animal model by adjusting the microbiome.

They first pretreated mice with antibiotics, which have been shown to alter the microbiota. After receiving vascularized cardiac allografts and tacrolimus immunosuppression, the mice were given a fecal microbiota transfer, which came from sample sources, including normal, colic (inflammation) and pregnant (immune suppressed) mice.

Species in the microbiota that displayed positive and negative effects were determined. For example, Bifidobacterium pseudolongum, a bacteria identified as anti-inflammatory, had a positive effect in mice that received a fecal microbiota transfer from pregnant mouse samples. In particular, B. pseudolongum transferred from pregnant mice samples were found to have much longer allograft survival and lower inflammation. 

Adjusting the microbiome showed improved vascularized cardiac allograft survival outcomes, which could have future implications for dealing with heart transplants and transforming outcomes.

“This work clearly shows that there is a connection between these gut microbes and the body’s response to the new organ. It’s very exciting,” said Emmanuel Mongodin, an associate professor of microbiology and immunology at the University of Maryland School of Medicine Institute for Genome Sciences.

Thus far, the researchers have only tested these microbiome adjustments and outcomes for heart transplants, but they believe that it could be similar for other organs, possibly solving part of the transplant rejection problem.