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NAFLD subtypes may be linked to gut dysbiosis, altered microbiota

Patients with severe nonalcoholic fatty liver disease, such as nonalcoholic steatohepatitis and fibrosis, were found to be independently associated with gut dysbiosis and altered gut microbiota, according to published findings.

“Recently, the gut microbiota has gained great attention in metabolic diseases since gut dysbiosis has been demonstrated in obesity, [metabolic syndrome], diabetes and cardiovascular diseases,” Jérôme Boursier, MD, PhD, Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire, France, and colleagues wrote. “Recent animal studies have placed the gut microbiota as a potentially important player in the pathogenesis of NAFLD. However, data linking gut dysbiosis with the severity of NAFLD remain poorly documented in humans.”

To evaluate the association between gut dysbiosis and severe NAFLD lesions, the researchers analyzed data of 57 adult patients with biopsy-proven NAFLD. The taxonomic composition of gut microbiota was determined via 16S ribosomal RNA gene sequencing of stool samples.

Overall, 30 patients had F0 or F1 stage fibrosis at liver biopsy (10 with NASH), and 27 patients had greater than F2 stage fibrosis (25 with NASH).

In patients with greater than F2 stage fibrosis, Bacteroides abundance was higher in those with NASH, whereas Prevotella abundance was lower, compared with patients without NASH. Ruminococcus abundance was higher in patients with greater than F2 stage fibrosis.

Multivariate analysis showed that Bacteroides abundance was independently associated with NASH and Ruminococcus was associated with greater than F2 stage fibrosis.

Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. “Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid and amino acid metabolism,” the researchers wrote.

The researchers concluded: “Histological subtypes of NAFLD that increase the risk for liver-related morbidity and mortality associate with gut dysbiosis and altered metabolic functions of the gut microbiota. Further studies will have to decipher how metabolic function of the gut microbiota might contribute to NASH and fibrosis in NAFLD.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.