A UCLA-led research team has found that giving mice antibiotics for 10 days prior to a liver transplant leads to better liver function after the surgery. After concluding the experiment on mice, the scientists discovered data from liver transplants performed between October 2013 and August 2015 at the Ronald Reagan UCLA Medical Center that revealed the same phenomenon appears to hold true in humans.
The researchers concluded that the antibiotics inhibited bacteria that cause inflammation, which in turn can lead to organ rejection. Specifically, they found that in both mice and humans, the treatment prior to a transplant reduced damage that could occur when blood flow is restored to the liver after a period of time without oxygen, and it reduced inflammation and cell damage while accelerating the removal of damaged cells. As a result, liver function was better than in the mice and human patients who did not receive antibiotics before a transplant.
Studies in the past four years at the University of Chicago and University of Maryland have shown that in mice that received antibiotics before skin or heart transplants, those transplants lasted longer without rejection than in mice that did not receive antibiotics pre-surgery. From those studies, the UCLA researchers were able to zero in on some bacteria that appeared to help ensure more successful transplants. In the mice that received antibiotics over the 10 days before transplants, the livers showed less damage — deterioration caused by dead cells, for example — than those in mice that were not given antibiotics before undergoing the same procedure.
To further substantiate the effect of the antibiotics, the researchers then transplanted fecal matter from the untreated mice into those that had been given the medication. The mice that received the fecal transplants suffered inflammatory damage to their livers, despite the fact that they had been given antibiotics earlier in the experiment. “That showed that antibiotic-mediated benefits clearly relate to the microbiota,” says Jerzy Kupiec-Weglinski, PhD, Paul I. Terasaki Professor of Surgery in the David Geffen School of Medicine at UCLA.
The data on the UCLA patients covered 264 people who had received liver transplants — 156 who, because they were sicker before their surgeries received antibiotics for 10 or more days prior to the transplant, and 108 who were given antibiotics for less than 10 days, or not at all prior to surgery. “To our total surprise, livers functioned better after transplantation in those patients who were very sick and required prolonged antibiotic therapy,” Dr. Kupiec-Weglinski says.
The researchers then narrowed their focus to human patients who had been given one specific antibiotic, rifaximin, prior to the transplants. (To pull together a larger sample size, the team analyzed data for transplants for a longer period of time than the original set of UCLA patients, from January 2013 through July 2016.) They found that in patients who received rifaximin, which stays in the bowel and has a low risk for inducing bacterial resistance, early liver failure was significantly delayed or stopped.
Dr. Kupiec-Weglinski says that the study opens the door to further research that could determine which microorganisms protect liver function after transplants and which bacteria need to be “turned down” to limit their negative effects.
— Enrique Rivero
“Antibiotic Pretreatment Alleviates Liver Transplant Damage in Mice and Humans,” Journal of Clinical Investigation, July 22, 2019