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A Comprehensive Review of Metabolic Dysfunction-Associated Steatotic Liver Disease: Its Mechanistic Development Focusing on Methylglyoxal and Counterbalancing Treatment Strategies
 
 
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10.3390/ijms26178165
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Distinct Gut Microbiota Signatures Are Associated with Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV

by
Riccardo Righetti
1,2,3,
Felice Cinque
1,
Bertrand Lebouché
1,2,
Luz Ramos Ballesteros
1,
Jean-Pierre Routy
1,2,
Marina B. Klein
1,2,
Jason Szabo
1,
Joseph Cox
1,2,
Julian Falutz
1,
Louis-Patrick Haraoui
4,
Cecilia T. Costiniuk
1,2,
Alexandra De Pokomandy
1,2,
Thomas Pembroke
5,
Marco Constante
6,
Manuela Santos
7 and
Giada Sebastiani
1,2,*
1
Chronic Viral Illness Service, Department of Medicine, McGill University Health Centre, Montréal, QC H4A 3J1, Canada
2
Infection and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada
3
Internal Medicine Unit, Department of Medical and Surgical Science for Children and Adults, Azienda Ospedaliero-Universitaria Policlinico di Modena, University of Modena and Reggio Emilia, 41125 Modena, Italy
4
Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
5
School of Medicine, Cardiff University, Cardiff CF14 4EP, UK
6
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
7
Department of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(17), 8165; https://doi.org/10.3390/ijms26178165
Submission received: 25 July 2025 / Revised: 19 August 2025 / Accepted: 20 August 2025 / Published: 22 August 2025
(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Metabolic-Associated Fatty Liver Diseases)
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Abstract

The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to severe forms, including metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis, involves metabolic dysfunction, genetics, and gut dysbiosis. People with HIV (PWH) represent a high-risk group for MASLD, but the role of gut microbiota alterations in disease severity within this population remains poorly understood. We prospectively recruited PWH with MASLD, defined as the controlled attenuation parameter (CAP) ≥ 238 dB/m, and excluded those with viral hepatitis coinfection or alcohol abuse. Severe MASLD was defined as the presence of MASH (cytokeratin-18 ≥ 130.5 U/L) and/or significant liver fibrosis (liver stiffness ≥ 7.1 kPa). Stool samples were collected for 16S rRNA gene sequencing to characterize gut microbiota composition. Functional predictions were generated using PICRUSt. The differential abundance of bacterial taxa and predicted functions were analyzed using a generalized linear model with a negative binomial distribution. Among 34 PWH with MASLD, 18 (53%) met the criteria for severe MASLD. Microbiota profiling revealed significant differences in bacterial genera between the PWH with and without severe MASLD. Enrichment was observed in the Ruminococcus gnavus group, Negativibacillus, Holdemanella, Subdoligranulum, the Eubacterium hallii group, and Butyricicoccus, while depletion was seen in Prevotella, Alloprevotella, Dialister, Catenibacterium, the Christensenellaceae R 7 group, Clostridium sensu stricto, Olsenella, Oscillospiraceae UCG-005, Libanicoccus, and the Eubacterium siraeum group. Predicted functional pathways related to fatty acid degradation, folate biosynthesis, and amino acids metabolism did not differ between groups. MASLD severity in PWH is associated with a distinct gut microbiota signature, though not with functional pathway alterations. Microbial profiling may complement existing non-invasive biomarkers for risk stratification in this high-risk population.
Keywords: microbiome; liver fibrosis; metabolic dysfunction-associated steatohepatitis; liver stiffness measurement; cytokeratin-18 microbiome; liver fibrosis; metabolic dysfunction-associated steatohepatitis; liver stiffness measurement; cytokeratin-18
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MDPI and ACS Style

Righetti, R.; Cinque, F.; Lebouché, B.; Ramos Ballesteros, L.; Routy, J.-P.; Klein, M.B.; Szabo, J.; Cox, J.; Falutz, J.; Haraoui, L.-P.; et al. Distinct Gut Microbiota Signatures Are Associated with Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV. Int. J. Mol. Sci. 2025, 26, 8165. https://doi.org/10.3390/ijms26178165

AMA Style

Righetti R, Cinque F, Lebouché B, Ramos Ballesteros L, Routy J-P, Klein MB, Szabo J, Cox J, Falutz J, Haraoui L-P, et al. Distinct Gut Microbiota Signatures Are Associated with Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV. International Journal of Molecular Sciences. 2025; 26(17):8165. https://doi.org/10.3390/ijms26178165

Chicago/Turabian Style

Righetti, Riccardo, Felice Cinque, Bertrand Lebouché, Luz Ramos Ballesteros, Jean-Pierre Routy, Marina B. Klein, Jason Szabo, Joseph Cox, Julian Falutz, Louis-Patrick Haraoui, and et al. 2025. "Distinct Gut Microbiota Signatures Are Associated with Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV" International Journal of Molecular Sciences 26, no. 17: 8165. https://doi.org/10.3390/ijms26178165

APA Style

Righetti, R., Cinque, F., Lebouché, B., Ramos Ballesteros, L., Routy, J.-P., Klein, M. B., Szabo, J., Cox, J., Falutz, J., Haraoui, L.-P., Costiniuk, C. T., De Pokomandy, A., Pembroke, T., Constante, M., Santos, M., & Sebastiani, G. (2025). Distinct Gut Microbiota Signatures Are Associated with Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease in People with HIV. International Journal of Molecular Sciences, 26(17), 8165. https://doi.org/10.3390/ijms26178165

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