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

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

Ana María Gómez-Pérez  1   2 , Patricia Ruiz-Limón  1   2 , Jordi Salas-Salvadó  2   3   4 , Jesús Vioque  5   6 , Dolores Corella  2   7 , Montse Fitó  2   8 , Josep Vidal  9   10 , Alessandro Atzeni  2   3   4 , Laura Torres-Collado  5   6 , Andrea Álvarez-Sala  2   7 , María Ángeles Martínez  2   3   4 , Albert Goday  2   8 , David Benaiges  2   8 , Jesús García-Gavilán  2   3   4 , María Rosa Bernal López  2   11 , Isabel Moreno-Indias  1   2 , Francisco J Tinahones  1   2
Affiliations
Clinical Trial

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

Ana María Gómez-Pérez et al. Gut Microbes. 2023 Jan-Dec.

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.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Graphs show the log10 values of the fold change in the abundance in phylum, family, and genera of gut microbiota found statistically significant between time-points (p < .05, q < 0.05). a. Significant changes in the abundance of gut microbiota in T1, T2 and T3 groups of HSI score. b. Significant changes in the abundance of gut microbiota in T1, T2 and T3 groups in FIB − 4 score.
Figure 2.
Figure 2.
Comparison among participants with non-suspected fibrosis (NSF) and paticipants with indeterminate or suspected fibrosis (SF). Relative abundance (%) of phyla, families and genera that have been found significant between fibrosis groups. Significantly differences *p ≤ .05.
Figure 3.
Figure 3.
Heatmap showing the means of changes in predicted pathways between the three HSI score tertiles. *Indicates significant differences between tertiles (p ≤ .05) and, $ indicates p < .1 in multiple group tests using the Kruskal–Wallis test.
Figure 4.
Figure 4.
Heatmap showing the means of changes in predicted pathways between three FIB−4 score tertiles. *Indicates significant differences between tertiles (p ≤ .05) in multiple group tests using the Kruskal–Wallis test.
See this image and copyright information in PMC

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