Giving mice antibiotics for 10 days before a liver transplant leads to better liver function after surgery, according to University of California, Los Angeles (UCLA) researchers. And data from liver transplants performed between 2013 and 2015 revealed that the same phenomenon appears to hold true in humans.
Further, the statistics showed that patients who were in worse health before their transplant but who received pre-surgery antibiotics fared better after surgery than patients who were healthier prior to surgery but who had received no antibiotics.
The researchers concluded that the antibiotics inhibit bacteria that causes inflammation, which can lead to organ rejection. In both mice and humans, antibiotic treatment before transplantation reduced the damage that could occur when blood flow is restored to the liver after being without oxygen for a time. It also reduced inflammation and cell damage, while accelerating the removal of damaged cells. Thus, liver function was better in these patients than in those who did not receive antibiotics before a transplant.
The researchers say the goal was to identify which bacteria are the beneficial ones.
Other studies have shown that transplants in mice that received antibiotics before skin or heart transplants lasted longer without rejection than transplants in mice that did not receive pre-surgery antibiotics. From those studies, the UCLA researchers were able to pinpoint some of the bacteria that appeared to help ensure more successful transplants.
In mice that received antibiotics, the livers were protected against transplant damage and rejection because the antibiotics modulated their host microbiomes, which in turn stimulated cell protection, according to the researchers.
To further substantiate the antibiotic effect, the researchers transplanted fecal matter from the untreated mice into those that had received the medication. The mice that received the fecal transplants suffered inflammatory damage to their livers, in spite of having been given antibiotics earlier in the experiment.
The data on the UCLA patients covered 264 people who had received liver transplant, including 156 who had received prior antibiotic treatment for 10 or more days prior to surgery because they were sicker, and 108 who were given antibiotics for less than 10 days or not at all prior to surgery.
Surprisingly, say the researchers, the livers functioned better after transplantation in the patients who were very sick and needed prolonged antibiotic therapy.
They then focused specifically on patients who had been given one particular antibiotic, rifaximin, prior to the transplants. 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.
Although the combination of data from human patients and mice demonstrate the benefits of extended pre-transplant antibiotic treatment, the researchers point out that longer-term studies are needed to strengthen their findings.
The research is published in the peer-reviewed Journal of Clinical Investigation.
Source: MedicalXpress, July 23, 2019