Sex-Dependent Gut Microbiota Features and Functional Signatures in Metabolic Disfunction-Associated Steatotic Liver Disease
<b>Background/Objectives</b>: This study investigates the gut microbiota's role in metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on microbial and functional signatures and sex-based differences. <b>Methods</b>: Using baseline data from 98 MASLD patients and 45 controls from the Fatty Liver in Obesity (FLiO) study, the gut microbiota was profiled with 16S gene sequencing, followed by statistical and machine learning analyses to identify disease-associated microbial signatures. <b>Results</b>: Notable alpha and beta diversity differences were observed between MASLD patients and the controls, varying by sex. Machine learning models highlighted specific microbial signatures for each sex, achieving high accuracy (area under the receiver operating characteristic curves of 0.91 for women and 0.72 for men). The key microbial taxa linked to MASLD included <i>Christensenella</i> and <i>Limosilactobacillus</i> in women and <i>Beduinibacterium</i> and <i>Anaerotruncus</i> in men. Functional profiling showed that MASLD patients had increased pathways for amine biosynthesis and amino acid degradation, while the controls exhibited enhanced fermentation pathways. These microbial features were associated with systemic inflammation, insulin resistance, and metabolite production linked to gut dysbiosis. <b>Conclusions</b>: The findings support the potential of gut microbiota signatures to be used as non-invasive indicators of MASLD and highlight sex-specific variations that could inform personalized diagnostic and therapeutic approaches.
Authors
- Josep A. Tur (ORCID: https://orcid.org/0000-0002-6940-0761)
- J.I. Herrero (ORCID: https://orcid.org/0000-0002-9076-6717)
- José Ignacio Riezu‐Boj (ORCID: https://orcid.org/0000-0002-1885-8457)
- Mariana Elorz (ORCID: https://orcid.org/0000-0002-1580-3629)
- Alberto Benito (ORCID: https://orcid.org/0000-0002-1527-0092)
- M. Ángeles Zulet (ORCID: https://orcid.org/0000-0002-3926-0892)
- Itziar Abete (ORCID: https://orcid.org/0000-0002-6475-5387)
- Fermı́n I. Milagro (ORCID: https://orcid.org/0000-0002-3228-9916)
- Pedro González‐Muniesa (ORCID: https://orcid.org/0000-0002-3130-2496)
- Paola Mogna-Peláez (ORCID: https://orcid.org/0000-0001-6058-312X)
- Iñigo Clemente‐Larramendi (ORCID: https://orcid.org/0009-0007-8037-5804)
- Ana Luz Tobaruela-Resola (ORCID: https://orcid.org/0009-0008-4484-8819)
- J. Alfredo Martínéz (ORCID: https://orcid.org/0000-0001-5218-6941)
- Sergio Esteban-Echeverría (ORCID: https://orcid.org/0009-0007-6512-0280)
Institutions
- Madrid Institute for Advanced Studies (ES)
- Instituto de Salud Carlos III (ES)
- Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Navarre Institute of Health Research (ES)
- Health Research Institute of the Balearic Islands (ES)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Clinica Universidad de Navarra (ES)
- Research Institute of Health Sciences (ES)
- IMDEA Food (ES)
- Universidad Autónoma de Madrid (ES)
- Universidad de Navarra (ES)
Publication Details
- Journal
- Nutrients
- Published
- 2024-12-04
- DOI
- https://doi.org/10.3390/nu16234198
- Citations
- 8
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.09
Funders
- Fundació la Marató de TV3
- Ministerio de Ciencia, Innovación y Universidades
- Gobierno de Navarra