Clin Mol Hepatol.
2025 Jan;31(1):179-195. 10.3350/cmh.2024.0359.
Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments
- Pirola CJ
1,2,3 - Landa MS2,4
- Schuman M2,4
- García SI2,4,5
- Salatino A6
- Sookoian S2,3,7
- Affiliations
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- 1Systems Biology of Complex Diseases, Translational Research in Health Center (CENITRES). Maimónides University, Buenos Aires, Argentin
- 2National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
- 3Faculty of Health Science, Maimónides University, Buenos Aires, Argentina
- 4University of Buenos Aires, School of Medicine, Institute of Medical Research A Lanari, Buenos Aires, Argentina
- 5Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina
- 6Max Planck Institute for Immunobiology and Epigenetics, Bioinformatics Facility, Frieburg, Germany
- 7Clinical and Molecular Hepatology, Translational Research in Health Center (CENITRES). Maimónides University, Buenos Aires, Argentina
- KMID: 2563419
- DOI: http://doi.org/10.3350/cmh.2024.0359
Abstract
- Background/Aims
Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis.
Methods
Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis.
Results
There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA p-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts.
Conclusions
This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.
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