Fecal microbiome signature detects cirrhosis in nonalcoholic fatty-liver disease

Last Updated: 2019-04-04

By Will Boggs MD

NEW YORK (Reuters Health) - A fecal microbiome signature accurately detects cirrhosis in patients with nonalcoholic fatty-liver disease (NAFLD), researchers report.

"A stool-microbiome signature could someday be a cost-effective way to screen at-risk populations for severe forms of NAFLD and identify those individuals who would benefit most from additional clinical support," said Dr. Rohit Loomba of the University of California, San Diego, in La Jolla.

"With the increasing numbers of NAFLD therapeutics entering the pipeline, this approach could also be a cost-effective way to accurately classify patients and enroll them in the most appropriate clinical trials," he told Reuters Health by email.

Most individuals with NAFLD, the commonest cause of chronic liver disease worldwide, remain undiagnosed, even those with advanced stages of the disease. Whether a gut-microbiome-derived signature could be useful for the noninvasive screening of advanced fibrosis or cirrhosis in high-risk individuals with NAFLD remains unknown.

Dr. Loomba's team evaluated MRI results and stool microbiome profiles from 98 individuals with NAFLD (probands) and 105 of their first-degree relatives in an effort to ascertain whether a noninvasive stool-microbiome-derived signature could accurately detect NAFLD-cirrhosis.

The microbiome profile showed significant correlation within biologically related pairs compared to random-unrelated pairs. When stratified by the liver phenotype of the proband, microbiome similarity remained significantly higher between non-NAFLD controls and their relatives and between probands with NAFLD without acute fibrosis and their relatives, whereas phylogenetic similarity did not differ significantly between probands with NAFLD-cirrhosis and their relatives.

Alpha-diversity of the microbiome profile decreased with increasing liver-damage severity, the researchers report in Nature Communications, online March 29.

Beta-diversity was lower among individuals with moderate liver damage (NAFLD without advanced fibrosis), compared with non-NAFLD controls, and it was higher among individuals with severe liver damage (NAFLD-cirrhosis) than among those with moderate liver damage.

A stool-microbiome signature composed of 27 bacterial features and age, sex and BMI identified probands with NAFLD-cirrhosis with 92% accuracy. The model also detected probands with advanced fibrosis with 87% accuracy and a negative predictive value of 91.6%.

In a separate validation group with mild to moderate NAFLD, including probands with NAFLD without advanced firbosis, the model had a diagnostic accuracy of 86%.

"As our microbiome diagnostic has been tested in only a small number of patients at a single study site, additional research in a larger population will be necessary well before a stool-based test for NAFLD could actually become available to patients," Dr. Loomba said. "Also, our study's findings do not necessarily mean the presence or absence of certain bacterial species causes NAFLD-cirrhosis. Additional research would be necessary to understand the link between particular microbial species and NAFLD."

According to a statement released with the study, "while (Dr.) Loomba estimates that a stool-based microbiome diagnostic might cost $1,500 if it were on the market today, he predicts that cost will lower to less than $400 in the next five years due to advances in genomic sequencing and analysis technologies."

Dr. Jonathan P. Jacobs from UCLA Microbiome Center at David Geffen School of Medicine, in Los Angeles, who recently reviewed the role of the gut microbiome in NAFLD, told Reuters Health by email, "What was unique about this study was the application of classifiers trained from patient data on relatives who were not previously known to have liver disease. A major limitation is that the classifier was only used to distinguish NAFLD cirrhosis from non-NAFLD, so it's unclear how effective it would be for differentiating NAFLD cirrhosis from NAFLD without advanced fibrosis."

"The most obvious potential application of the NAFLD cirrhosis microbiome signature would be as a screening tool to identify those who may have NAFLD cirrhosis among populations of individuals at risk (e.g., patients with metabolic syndrome)," he said. "This would potentially be more cost-effective and scalable than current imaging-based modalities."

"There is a potential to use microbiome profiles for diagnosis, but without a head-to-head comparison of test characteristics, it's unclear how well stool-microbiome profiles would fare against existing imaging modalities that are used to noninvasively diagnose NAFLD cirrhosis (of note, NAFLD and NAFLD cirrhosis were diagnosed in the validation cohort of first-degree relatives by imaging only)," said Dr. Jacobs, who was not involved in the study.

"Another promising potential biomarker application of fecal microbial signatures would be to identify the subset of patients without current advanced fibrosis who are at the highest risk for progression to advanced fibrosis," he said. "If indeed the microbiome drives NAFLD progression, a detectable signature should precede fibrosis. Such patients might warrant more aggressive lifestyle and/or pharmacologic therapy for their NAFLD to prevent progression to fibrosis."

SOURCE: https://bit.ly/2K2ZiSU

Nat Commun 2019.