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

Gut Microbes. 2023 Jan-Dec;15(1):2223339. doi: 10.1080/19490976.2023.2223339.

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 (n = 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 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.

Keywords: Mediterranean diet; Microbiome; hepatic steatosis index; metabolic liver disease; the Fibrosis-4 score.

Plain language summary

What You Need to KnowWhat 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibrosis
  • Gastrointestinal Microbiome*
  • Humans
  • Liver / metabolism
  • Metabolic Syndrome* / metabolism
  • Non-alcoholic Fatty Liver Disease* / microbiology

Grants and funding

This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (three coordinated FIS projects lead by JS-S: PI13/00462, PI16/00501 and PI19/00576; two led by JV: PI17/01441, PI14/01206; three led by AG: PI13/00233, PI16/00533, PI19/00017; and two led by MRBL: PI14/00696 and PI17/00855); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant (OBN16PE01) to JS-S; the Recercaixa (number 2013ACUP00194) grant to JS-S. DC obtained grant from the Generalitat Valenciana (PROMETEO 2017/17 and PROMETEO 2021/21) and Grant from the Ministry of Science and Innovation/ISCIII (reference: PI19/00781). Eat2beNICE project (European Union’s Horizon 2020 research and innovation programme under grant agreement No 728018). PRL was supported by a “Sara Borrell” postdoctoral contract (CD19/00216) from the ISCIII-Madrid (Spain), co-financed by the Fondo Europeo de Desarrollo Regional-FEDER. IMI was supported by the “Miguel Servet Type II” program (CPII21/00013) of the ISCIII-Madrid (Spain), co-financed by the FEDER. AMGP was supported by a research contract from Servicio Andaluz de Salud (B-0033–2014). AA-S has received a post-doctoral grant (APOSTD/2020/164) from the Consellería de Innovación, Generalitat Valenciana. MRBL is supported by Miguel Servet II program (CPII/00014) from ISCIII and by Nicolás Monardes program (C1-0005-2020) from Servicio Andaluz de Salud, both cofunded by FEDER funds. This work is partially supported by ICREA under the ICREA Academia programme. Food companies Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) donated extra virgin olive oil; and the Almond Board of California (Modesto, CA, USA), American Pistachio Growers (Fresno, CA, USA), and Paramount Farms (Wonderful Company, LLC, Los Angeles, CA, USA) donated nuts for the PREDIMED-Pilot study.