Cross talk between the liver microbiome and epigenome in patients with 
metabolic dysfunction-associated steatotic liver disease

Pirola, Carlos Jose; Salatino, Adrian; Gianotti, Tomas Fernández; Castaño, Gustavo Osvaldo; Garaycoechea, Martin; Sookoian, Silvia

doi:10.1016/j.ebiom.2024.104996

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Cross talk between the liver microbiome and epigenome in patients with metabolic dysfunction-associated steatotic liver disease

MPS-Authors

Salatino, Adrian
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

https://www.sciencedirect.com/science/article/pii/S2352396424000318?via%3Dihub
(Publisher version)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

10.1016_j.ebiom.2024.104996.pdf
(Publisher version), 2MB

Supplementary Material (public)

There is no public supplementary material available

Citation

Pirola, C. J., Salatino, A., Gianotti, T. F., Castaño, G. O., Garaycoechea, M., & Sookoian, S. (2024). Cross talk between the liver microbiome and epigenome in patients with metabolic dysfunction-associated steatotic liver disease. EBioMedicine, 101: 104996. doi:10.1016/j.ebiom.2024.104996.

Cite as: https://hdl.handle.net/21.11116/0000-000F-394B-E

Abstract

Background: The pathogenesis of MASLD (metabolic dysfunction-associated steatotic liver disease), including its severe clinical forms, involves complex processes at all levels of biological organization. This study examined the potential link between the liver microbiome profile and epigenetic factors.

Methods: Liver microbial DNA composition was analysed using high throughput 16S rRNA gene sequencing in 116 individuals, with 55% being female, across the spectrum of liver disease severity. Total activity of histone deacetylases (HDACs) and acetyltransferases (HATs) was assayed in nuclear extracts from fresh liver samples. In addition, we measured the global 5-hydroxymethylcytosine (5-hmC) levels of liver DNA.

Findings: Patients with MASLD showed a 2.07-fold increase (p = 0.013) in liver total HAT activity. Moreover, a correlation was observed between liver total HAT activity and the score for histological steatosis (Spearman's R = 0.60, p = 1.0E-3) and disease severity (R = 0.40, p = 2.0E-2). Liver HAT and HDAC activities also showed associations with the abundance of several liver bacterial DNAs. Additionally, liver global levels of 5-hmC showed negative correlation with the read number of Bacteroidetes (R = -0.62, p = 9.3E-4) and Gammaproteobacteria (R = -0.43, p = 3.2E-2), while it was positively correlated with the abundance of Acidobacteria (R = 0.42, p = 4.1E-2) and Actinobacteria (R = 0.47, p = 1.8E-2).

Interpretation: The host liver epigenome, including the activity of enzymes involved in maintaining the balance between protein acetylation and deacetylation and the global DNA hydroxy-methylation status, may be the target of microbial signals.

Funding: Agencia Nacional de Promoción Científica y Tecnológica, FonCyT.