The substances created by the gut’s microbial community influence the immune defenses in the intestinal lining and enhance the function of the protective layer on the surface. When there’s an imbalance in the gut bacteria, known as intestinal dysbiosis, characterized by a reduction in microbial diversity and an increase in antibiotic-resistant harmful bacteria, it leads to changes in the concentration of substances in feces and a higher risk of systemic infections. Currently, clinical tests measuring intestinal dysbiosis are not commonly used in healthcare.
In a new study, scientists at the University of Chicago predicted postoperative infections in liver transplant patients by analyzing molecules in their poop. The examination they conducted is a significant advancement in understanding how the gut microbiome, the bacteria living in the human body, is linked to overall health.
Scientists analyzed fecal samples from over 100 liver transplant patients to see if the microbiome could influence their infection risk.
They discovered a wide range of microbiome compositions in different patients.
Christopher Lehmann, MD, an assistant professor of medicine at UChicago Medicine and lead author, said, “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.”
“The human microbiome, particularly the gut microbiome, has adapted to fight off drug-resistant bacteria throughout history. We need to try to understand how that works to fight off these drug-resistant infections.”
“A healthy microbiome would comprise over a trillion bacterial cells, with thousands of unique species — like a diverse rainforest. Some patients have that entire ecosystem wiped out. They still have over a trillion cells, but there’s only one bacterial species — usually a bad, drug-resistant one. It would be like clear-cutting the rainforest and planting nothing but a single harmful weed species.”
The scientists discovered that healthy microbiomes generate crucial metabolites, including beneficial short-chain fatty and secondary bile acids. The bacteria modify human bile acids to create these secondary bile acids, which are advantageous to human hosts.
Interestingly, in a diverse microbiome, these bile acids play a role in combating drug-resistant bacteria. Certain bile acids are particularly toxic to bacteria like vancomycin-resistant Enterococcus (VRE), an antibiotic-resistant bacteria often responsible for infections in patients undergoing surgery, cancer treatment, or intensive care.
Scientists next determined their data to see if there was a correlation between microbiome composition and postoperative infections.
Lehmann said, “It turned out that the amount of drug-resistant pathogens in the microbiome predicted postoperative infections with an accuracy we’d normally be looking for in a clinical test.”
Taking their research further, the team examined the metabolites in patients’ feces instead of sequencing genomes to identify individual bacterial species. Strikingly, by solely focusing on the metabolites, they could effectively categorize patients into two groups: healthy and unhealthy microbiomes. Going even further analytically, they discovered that these metabolites could be used to predict whether a patient was likely to develop an infection.
Lehmann said, “We can go straight from metabolites to predicting a clinical outcome. This is important because metabolomic analysis can be performed quickly, whereas sequencing is relatively slow.”
The current analytical algorithm is complex and requires thorough validation before being employed as a diagnostic or predictive test in clinical settings. Nevertheless, these discoveries provide a foundation for future research that may further establish the link between infections and metabolites in feces. Additionally, future studies could explore potential causal relationships in this context.
Lehmann said, “The next step of this course of research will be investigating whether we can use these findings to correct people’s microbiomes.”
“Patients with unhealthy, single-species gut microbiomes and are at high risk of infection could potentially receive healthy gut bacteria from external sources restore production of healthy metabolites, including molecules like the secondary bile acids that can help protect against drug-resistant infections.”
“We’ve already made a handful of cocktails of bacteria that are missing from patients with bad outcomes but present in patients with good outcomes. Those bacteria can work together to make the metabolites that were missing in patients that got infections. Then they can inhabit the gut and theoretically defend against future negative outcomes.”
Journal Reference:
- Christopher J. Lehmann, Nicholas P. Dylla, Matthew Odenwald et al. Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection. Cell Host & Microbe. DOI: 10.1016/j.chom.2023.11.016