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

Abstract

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 (<i>n</i> = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) 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 <i>Alcaligenaceae</i>, <i>Bacteroidaceae</i>, <i>Bifidobacteriaceae</i>, <i>Clostridiaceae</i>, <i>Enterobacteriaceae</i>, <i>Peptostreptococcaceae</i>, <i>Verrucomicrobiaceae</i> 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 <i>Akkermansia</i> and an increase in <i>Desulfovibrio</i>. T2 had an increase in <i>Victivallaceae</i>, <i>Clostridiaceae</i>, and <i>Desulfovibrio</i>. T3 showed a decrease in <i>Enterobacteriaceae</i>, and an increase in <i>Sutterella</i>, <i>Faecalibacterium</i>, and <i>Blautia</i>. 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.