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Vidal, JAuthorAtzeni, AAuthor

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January 3, 2024
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Article

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

Publicated to: Gut Microbes. 15 (1): 2223339- - 2023-12-31 15(1), DOI: 10.1080/19490976.2023.2223339

Authors:

Gomez-Perez, Ana Maria; Ruiz-Limon, Patricia; Salas-Salvado, Jordi; Vioque, Jesus; Corella, Dolores; Fito, Montse; Vidal, Josep; Atzeni, Alessandro; Torres-Collado, Laura; Alvarez-Sala, Andrea; Angeles Martinez, Maria; Goday, Albert; Benaiges, David; Garcia-Gavilan, Jesus; Bernal Lopez, Maria Rosa; Moreno-Indias, Isabel; Tinahones, Francisco J
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Affiliations

August Pi I Sunyer Biomed Res Inst IDIBAPS, Endocrinol & Nutr Dept, Barcelona, Spain - Author
Carlos III Hlth Inst, CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain - Author
Carlos III Hlth Inst, CIBER Physiopathol Obes & Nutr CIBEROBN, Madrid, Spain - Author
Clin Univ Hosp, Endocrinol & Nutr Dept, Barcelona, Spain - Author
Hosp del Mar Res Inst IMIM, Cardiovasc Risk & Nutr Regicor Study Grp, Barcelona, Spain - Author
Pere & Virgili Hlth Res Inst IISPV, Human Nutr Unit, Reus, Spain - Author
Reg Univ Hosp, Inst Biomed Res Malaga IBIMA, Dept Internal Med, Malaga, Spain - Author
Univ Malaga, Virgen Victoria Univ Hosp, Biomed Res Inst Malaga & Platform Nanomed IBIMA B, Dept Endocrinol & Nutr, Malaga, Spain - Author
Univ Miguel Hernandez ISABIAL UMH, Inst Hlth & Biomed Res Alicante, Alicante, Spain - Author
Univ Rovira & Virgili, Dept Biochem & Biotechnol, Human Nutr Unit, Reus, Spain - Author
Univ Valencia, Dept Prevent Med, Valencia, Spain - Author
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Abstract

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.
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Keywords

AcidAdultAkkermansiaAlanine aminotransferaseAlcaligenaceaeAlkaline phosphataseAnthropometryArticleAspartate aminotransferaseBacteroidaceaeBifidobacteriaceaeBody massBody weight lossCardiovascular diseaseCholesterol blood levelClinical trial (topic)ClostridiaceaeControlled studyDesulfovibrioDiastolic blood pressureDna extractionEnterobacteriaceaeFaecalibacteriumFatty liverFeces analysisFeces microfloraFemaleFibrosisFibrosis 4 scoreGamma glutamyltransferaseGastric bypassGastrointestinal microbiomeHepatic steatosis indexHigh density lipoproteinHumanHumansHypercholesterolemiaHypertensionInterventionIntestine floraLiverLow density lipoproteinLow density lipoprotein cholesterolMajor clinical studyMaleMediterranean dietMetabolic liver diseaseMetabolic syndromeMetabolic syndrome xMetabolismMetforminMicrobiologyMicrobiomeNon-alcoholic fatty liver diseaseNonalcoholic fatty liverPeptostreptococcaceaePhylogenyPredictive valueRna 16sScoring systemSoftwareSystolic blood pressureThe fibrosis-4 scoreTriacylglycerolWaist circumferenceWaist hip ratio

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Gut Microbes due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 8/143, thus managing to position itself as a Q1 (Primer Cuartil), in the category Gastroenterology & Hepatology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 6.97. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 2.27 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-05, the following number of citations:

  • WoS: 38
  • Scopus: 15
  • Europe PMC: 22
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-05:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 63.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 63 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 13.
  • The number of mentions on the social network X (formerly Twitter): 8 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Awards linked to the item

This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion 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: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica 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 Conselleria de Innovacion, Generalitat Valenciana. MRBL is supported by Miguel Servet II program (CPII/00014) from ISCIII and by Nicolas 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.
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