A stool test for cirrhosis

UC San Diego researchers analyze stool microbes to diagnose liver disease

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SAN DIEGO—For those with nonalcoholic fatty liver disease (NAFLD), finding out whether or not they have liver cirrhosis or scarring is an important predictor for survival, yet it’s difficult and invasive to detect liver cirrhosis before it’s well advanced.
In an effort to quickly and easily identify people at high risk for NAFLD-cirrhosis, researchers in the NAFLD Research Center and Center for Microbiome Innovation at the University of California, San Diego (UC San Diego) identified unique patterns of bacterial species in the stool of people with the condition. The study was published in Nature Communications.
“If we are better able to diagnose NAFLD-related cirrhosis, we will be better at enrolling the right types of patients in clinical trials, and ultimately will be better equipped to prevent and treat it,” stated senior author Dr. Rohit Loomba, a professor of medicine in the Division of Gastroenterology at the UC San Diego School of Medicine, director of the NAFLD Research Center and a faculty member in the Center for Microbiome Innovation at UC San Diego. “This latest advance toward a noninvasive stool test for NAFLD-cirrhosis may also help pave the way for other microbiome-based diagnostics and therapeutics, and better enable us to provide personalized, or precision, medicine for a number of conditions.”
The precise cause of NAFLD is unknown, but both diet and genetics play substantial roles. Up to 50 percent of obese people are believed to have NAFLD, and people with a first-degree relative with NAFLD are at increased risk for the disease themselves.
In a previous proof-of-concept study of patients with biopsy-proven NAFLD, Loomba and colleagues found a gut microbiome pattern that distinguished mild/moderate NAFLD from advanced disease, allowing the team to predict which patients had advanced disease with high accuracy. In this latest study, Loomba’s team wanted to test if a similar stool-based readout of a person with NAFLD’s microbiome content might provide insight into their cirrhosis status.
The researchers analyzed the microbial makeup of stool samples from 98 people known to have some form of NAFLD and 105 of their first-degree relatives, including some twins. They did this by sequencing the 16S rRNA gene, a genetic marker specific to bacteria and their relatives, archaea. The 16S rRNA sequences serve as markers to identify different types of bacteria and the relative amounts of each.
Researchers found that people who share a home tended to share similar microbial patterns in their microbiomes, further validating several previous studies. They also observed that people with extreme forms of NAFLD had less diverse and less stable gut microbiomes.
“In line with previous studies, we observed an initial decrease in both alpha and beta diversity in the moderate stage of NAFLD. Interestingly, we observed a decrease in alpha-diversity and increase in beta-diversity in severe stage of disease (NAFLD-cirrhosis) compared to NAFLD without AF [advanced fibrosis],” the article says. “This suggests that the extreme form of disease is characterized by a less diverse but also significantly less stable microbiome.”
The team identified 27 unique bacterial features unique to the gut microbiomes and stool of people with NAFLD-cirrhosis, and researchers were able to use this noninvasive test to pick out the people with known NAFLD-cirrhosis with 92-percent accuracy. More importantly, the test allowed them to differentiate the first-degree relative with previously undiagnosed NAFLD-cirrhosis with 87-percent accuracy.
The researchers caution that so far this new diagnostic approach has only been tested in a relatively small patient group at a single specialized medical center, and pointed out that if successful, a stool-based test for NAFLD wouldn’t be available to patients for at least five years.
The article notes that “due to the single-center design, the generalization of the gut-microbiome signature in population from other geographical locations is unknown. Finally, the association does not suggest causality, and additional studies are needed to assess whether these microbial species impact gut permeability and/or induce NAFLD progression through cross-talk between serum metabolites and the liver.”
Loomba also explained that while a distinct set of microbial species may be associated with advanced NAFLD-cirrhosis, this study does not suggest that the presence or absence of these microbes causes NAFLD-cirrhosis, or vice versa.

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