What is already known
Accounting for more than two million deaths every year, liver diseases — including liver fibrosis and liver cancer — are on the rise. For most of these conditions, liver transplant is often the only therapeutic option. However, liver transplant is complicated by high rates of infections that have been linked to gut microbes.
What this research adds
Researchers analyzed stool samples from 107 people undergoing liver transplant and then associated the presence of specific microbial metabolites with the microbiota composition as well as with the occurrence of infections. Reduced stool levels of metabolites such as short-chain fatty acids and secondary bile acids were linked to alterations of the gut microbiota and to a higher risk of infection after liver transplant.
Conclusions
The findings suggest that microbial metabolites can help to predict who is at increased risk of infection after liver transplant. The results may also help to inform microbiota-targeted therapies.
Liver transplants can save the lives of people with severe liver diseases, but these procedures are often complicated by high rates of infections that have been linked to gut microbes. Now, researchers have found that profiling the microbial metabolites in stool samples may be a viable tool for predicting postoperative infections in patients who received liver transplants.
The findings, published in Cell Host & Microbe, suggest that microbial metabolites can help to predict who is at increased risk of infection after liver transplant. The results may also help to inform microbiota-targeted therapies.
Liver transplant is often the only therapeutic option for liver diseases — including liver fibrosis and liver cancer, which account for more than two million deaths every year. However, patients receiving liver transplants are especially susceptible to drug-resistant infections.
“Antibiotic resistance is growing every year and getting worse. Without antibiotics that work, we can’t do things like perform surgeries, protect premature infants or treat cancer,” says study lead investigator Christopher Lehmann at University of Chicago Medicine in Chicago. “It turns out the human microbiome, particularly the gut microbiome, has adapted to fight off drug-resistant bacteria over the course of history. We need to try to understand how that works to fight off these drug-resistant infections.”
To investigate whether the microbiota could influence a person’s risk of developing an infection after liver transplant, Lehmann and his colleagues analyzed stool samples from 107 people undergoing this surgical procedure.
Metabolite alterations
The researchers determined the microbiota composition of each person and divided the study participants into three groups based on their microbial diversity. People with alcoholic cirrhosis and end-stage liver disease had lower microbial diversity, whereas those with liver cancer and chronic hepatitis C tended to have a higher diversity. People with medium or low diversity had reduced levels of beneficial bacterial and higher abundances of Enterococcus and Enterobacterales species.
The team also analyzed the microbial metabolites present in the participants’ stool samples.
Short-chain fatty acids and branched-chain fatty acids, which are products of amino acid fermentation, were reduced in people with low and medium microbial diversity. These individuals also had reduced concentrations of secondary bile acids, which result from bacterial actions in the colon.
Microbiota-derived vitamins such as biotin, niacin and folate were reduced in low-diversity patients — a finding that likely reflects the loss of gut bacteria that produce B vitamins.
Infection risk
Next, the researchers associated the presence of specific microbial metabolites with the microbiota composition as well as with the occurrence of post-operative infections in patients who received liver transplants.
Reduced stool levels of metabolites such as short-chain fatty acids and secondary bile acids were linked to alterations of the gut microbiota and to a higher risk of infection after liver transplant, the researchers found.
“Fecal metabolite measurement identified patients at risk for postoperative infection and associated specific metabolites with infection,” the authors say. “The ability to rapidly identify patients with an increased risk of postoperative infection should facilitate the development of strategies that preserve or reconstitute microbiome functions and lead to approaches that prevent exposure to antibiotic-resistant pathobionts.”
