WASHINGTON (FRONTLINE MEDICAL NEWS) – A newly identified metabolite of the gut microbiome may be a potentially useful biomarker in determining the severity of nonalcoholic fatty liver disease (NAFLD) and may provide a new treatment target, according to results of an analysis of serum metabolites isolated from 100 pairs of twins presented at the annual meeting of the American Association for the Study of Liver Diseases.

The researchers at the NAFLD Research Center at the University of California at San Diego isolated a metabolite derived from the gut microbiome, known as 3-(4-hydroxyphenyl)lactate, from 713 serum metabolites they analyzed, 440 of which were identified as heritable, said Cyrielle Caussy, MD, PhD. The researchers further winnowed that pool down to 94 associated with fibrosis alone and 170 associated with hepatic steatosis alone, 56 of which overlapped to have a shared gene effect with both hepatic steatosis and fibrosis, six of which derived from the gut microbiome.

“We wanted to know if these serum metabolites are associated with advanced fibrosis,” Dr. Caussy said. “Only one is associated with advanced fibrosis in this cohort. It is 3-(4-hydroxyphenyl)lactate.” Rohit Loomba, MD, MHSc, director of the NAFLD Research Center , is the principal investigator of the study.

Of the four heritable serum metabolites the researchers found to be significantly associated with NAFLD after adjustment for age, sex and Hispanic ethnicity, 3-(4-hydroxyphenyl)lactate had the highest odds ratio (95% confidence interval): 4.29 (1.87-9.81, P = .0006) vs. phenyllactate (OR 2.12, 1.09-4.10, P = .0258), palmitic acid (2.58, 1.31-5.17, P = .0065) and gamma-glutamylisoleucine (2.98, 1.36-6.51, P = .0062).

Dr. Caussy noted that previous studies have found a strong correlation between bacterial species in the gut and advanced fibrosis in NAFLD ( Cell Metab. 2017;25:1054-62 ). This latest research takes those findings to the next level, Dr. Caussy said. “This metabolite could be a useful biomarker of the severity of NAFLD and may be a target for future treatment of NAFLD and could be used to monitor a treatment response,” she added.

The goal of the study was to determine if any serum metabolites have a shared genetic effect with hepatic steatosis and fibrosis, Dr. Caussy said. “The heritability of serum metabolites associated with NAFLD and their shared gene effect with hepatic steatosis and fibrosis have not been assessed yet,” she noted. The researchers isolated the serum metabolites from a cohort of 100 pairs of twins and 56 other relatives in the Southern California Twins Register, and validated the data in a cohort of 156 patients who had biopsy-proven NAFLD.

Dr. Caussy reported having no financial disclosures.


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