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  Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments

Pirola, C. J., Landa, M. S., Schuman, M., García, S. I., Salatino, A., & Sookoian, S. (2024). Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments. Clinical and molecular hepatology: CMH / Korean Association for the Study of the Liver, 31, 179-195. doi:10.3350/cmh.2024.0359.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0010-C79D-D Version Permalink: https://hdl.handle.net/21.11116/0000-0010-C79E-C
Genre: Journal Article

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10.3350_cmh.2024.0359.pdf (Publisher version), 7MB
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https://hdl.handle.net/21.11116/0000-0010-C79F-B
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10.3350_cmh.2024.0359.pdf
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Copyright Date:
2025
Copyright Info:
The Korean Association for the Study of the Liver
License:
https://creativecommons.org/licenses/by-nc/3.0/

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https://e-cmh.org/journal/view.php?doi=10.3350/cmh.2024.0359 (Publisher version)
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 Creators:
Pirola, Carlos Jose1, Author
Landa, Maria Silvina1, Author
Schuman, Mariano1, Author
García, Silvia Inés1, Author
Salatino, Adrian2, Author
Sookoian, Silvia1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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Free keywords: Gut microbiome; MASLD; Metabolic syndrome; NAFLD; Sexual dimorphism
 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.

Conclusion: 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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Language(s): eng - English
 Dates: 2024-10-11
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.3350/cmh.2024.0359
 Degree: -

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Title: Clinical and molecular hepatology : CMH / Korean Association for the Study of the Liver
  Abbreviation : Clin Mol Hepatol
Source Genre: Journal
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Publ. Info: Seoul : Seoul : Assoc.
Pages: - Volume / Issue: 31 Sequence Number: - Start / End Page: 179 - 195 Identifier: ISSN: 2287-285X
CoNE: https://pure.mpg.de/cone/journals/resource/2287-285X