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Gut microbiome metabolite linked to hepatic steatosis, fibrosis

The microbial metabolite 3-(4-hydroxyphenyl)lactate, linked to multiple bacterial phylum in the gut microbiome, correlated significantly with liver fibrosis and demonstrated a shared gene-effect with hepatic steatosis and fibrosis, according to a recently published study on nonalcoholic fatty liver disease.

“Utilizing a uniquely, well-characterized, discovery cohort of community-dwelling twins and families, and a validation cohort of patients with biopsy-proven NAFLD, we report the association between a novel gut microbiome-derived serum metabolite, 3-(4-hydroxyphenyl) lactacte that has a statistically and clinically significant shared gene-effect with both hepatic steatosis and fibrosis,” Cyrielle Caussy, MD, PhD, from the NAFLD Research Center in California, and colleagues wrote.

Caussy and colleagues sought to verify heritability and shared gene-effect between serum metabolites and hepatic steatosis and fibrosis, and whether any of these metabolites derived from the gut microbiome.

The study comprised 156 participants, including 50 twin pairs and 56 siblings or parents of the twins. Participants underwent serum metabolite assessment, clinical evaluation and advanced MRI. The study also included a validation cohort of 156 participants recruited from the University of California San Diego NALFD Research Center.

The researchers analyzed 713 serum metabolites in the twin participants, of which 440 were heritable. Among the heritable serum metabolites, 56 had a significant shared gene-effect with both hepatic steatosis and fibrosis. Six of the significant shared gene-effect metabolites had microbial origin and potentially derived from the gut microbiome.

Finally, the researchers found that the metabolite 3-(4-hydroxyphenyl)lactate correlated significantly with hepatic fibrosis in both the twin cohort according to magnetic resonance elastography (r = 0.25; P < .001) and the validation cohort according to liver biopsy (r = 0.25; P = .002).

The association between 3-(4-hydroxyphenyl)lactate and hepatic steatosis and fibrosis remained significant after adjusting for age, sex, obesity and ethnicity.

Regarding the gut microbiome, 3-(4-hydroxyphenyl)lactate correlated with a multitude of bacterial species that belong to the Firmicutes, Bacteroidetes and Proteobacteria phyla, after adjusting for age and sex.

“The Twin and Family cohort allows for the assessment of the heritability estimates and shared gene-effects using accurate and reproducible non-invasive imaging biomarker for the quantification of hepatic steatosis and fibrosis,” the researchers wrote. “Further longitudinal studies are needed to determine the role of 3-(4-hydroxyphenyl)lactacte in the development of NAFLD and whether 3-(4-hydroxyphenyl)lactacte is a reliable biomarker associated with longitudinal changes in hepatic steatosis and fibrosis.” – by Talitha Bennett

Disclosure: Caussy reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.