Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma

Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The gut microbiome interacts with the liver via a bidirectional relationship with the gut–liver axis. Microbial metabolites...

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Main Authors: Mahmoud Zhra, Muhammad Affan Elahi, Aamira Tariq, Ahmed Abu-Zaid, Ahmed Yaqinuddin
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/14/6/466
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author Mahmoud Zhra
Muhammad Affan Elahi
Aamira Tariq
Ahmed Abu-Zaid
Ahmed Yaqinuddin
author_facet Mahmoud Zhra
Muhammad Affan Elahi
Aamira Tariq
Ahmed Abu-Zaid
Ahmed Yaqinuddin
author_sort Mahmoud Zhra
collection DOAJ
description Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The gut microbiome interacts with the liver via a bidirectional relationship with the gut–liver axis. Microbial metabolites, sirtuins, and immune responses are pivotal in different metabolic diseases. This extensive review explores the complex and multifaceted interrelationship between sirtuins and gut microbiota, highlighting their importance in health and disease, particularly metabolic dysfunction and hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as a group of NAD<sup>+</sup>-dependent deacetylases, serve as crucial modulators of a wide spectrum of cellular functions, including metabolic pathways, the inflammatory response, and the process of senescence. Their subcellular localization and diverse functions link them to various health conditions, including NAFLD and cancer. Concurrently, the gut microbiota, comprising diverse microorganisms, significantly influences host metabolism and immune responses. Recent findings indicate that sirtuins modulate gut microbiota composition and function, while the microbiota can affect sirtuin activity. This bidirectional relationship is particularly relevant in metabolic disorders, where dysbiosis contributes to disease progression. The review highlights recent findings on the roles of specific sirtuins in maintaining gut health and their implications in metabolic dysfunction and HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked to metabolic dysregulation and liver pathology.
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spelling doaj-art-02b7527d2ad046e3ab66a7874e55d08a2025-08-20T02:11:01ZengMDPI AGCells2073-44092025-03-0114646610.3390/cells14060466Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular CarcinomaMahmoud Zhra0Muhammad Affan Elahi1Aamira Tariq2Ahmed Abu-Zaid3Ahmed Yaqinuddin4Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi ArabiaDepartment of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi ArabiaDepartment of Biosciences, COMSATS University Islamabad, Islamabad Campus, Islamabad 45550, PakistanDepartment of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi ArabiaDepartment of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi ArabiaMetabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The gut microbiome interacts with the liver via a bidirectional relationship with the gut–liver axis. Microbial metabolites, sirtuins, and immune responses are pivotal in different metabolic diseases. This extensive review explores the complex and multifaceted interrelationship between sirtuins and gut microbiota, highlighting their importance in health and disease, particularly metabolic dysfunction and hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as a group of NAD<sup>+</sup>-dependent deacetylases, serve as crucial modulators of a wide spectrum of cellular functions, including metabolic pathways, the inflammatory response, and the process of senescence. Their subcellular localization and diverse functions link them to various health conditions, including NAFLD and cancer. Concurrently, the gut microbiota, comprising diverse microorganisms, significantly influences host metabolism and immune responses. Recent findings indicate that sirtuins modulate gut microbiota composition and function, while the microbiota can affect sirtuin activity. This bidirectional relationship is particularly relevant in metabolic disorders, where dysbiosis contributes to disease progression. The review highlights recent findings on the roles of specific sirtuins in maintaining gut health and their implications in metabolic dysfunction and HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked to metabolic dysregulation and liver pathology.https://www.mdpi.com/2073-4409/14/6/466sirtuins (SIRTs)gut microbiotametabolic dysfunctionhepatocellular carcinoma (HCC)non-alcoholic fatty liver disease (NAFLD)
spellingShingle Mahmoud Zhra
Muhammad Affan Elahi
Aamira Tariq
Ahmed Abu-Zaid
Ahmed Yaqinuddin
Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma
Cells
sirtuins (SIRTs)
gut microbiota
metabolic dysfunction
hepatocellular carcinoma (HCC)
non-alcoholic fatty liver disease (NAFLD)
title Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma
title_full Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma
title_fullStr Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma
title_full_unstemmed Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma
title_short Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma
title_sort sirtuins and gut microbiota dynamics in health and a journey from metabolic dysfunction to hepatocellular carcinoma
topic sirtuins (SIRTs)
gut microbiota
metabolic dysfunction
hepatocellular carcinoma (HCC)
non-alcoholic fatty liver disease (NAFLD)
url https://www.mdpi.com/2073-4409/14/6/466
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