Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis

Plain Language Summary What You Need to Know What is the context: Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD. What is new: Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB-4) in only one year. A relation between the changes in these scores and gut microbiota changes was found. What is the impact: The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD. To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevencion con Dieta Mediterranea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.

Automated summary

This study found that the Mediterranean diet and physical activity can change the scores for liver steatosis and liver fibrosis within one year, and these changes are related to changes in gut microbiota. The findings are important for identifying microbiota-based biomarkers for NAFLD and developing strategies to modulate gut microbiota in the treatment of NAFLD.