Title:Gut Microbiota Dysbiosis in the Pathogenesis of Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD)
Volume: 3
Author(s): Gh Jeelani Mir and Nissar Ul Ashraf*
Affiliation:
- Department
of Biochemistry, Government College for Women, Nawakadal, Srinagar, Jammu & Kashmir, 190002, India
Keywords:
MASLD/NAFLD, MASH/NASH, Insulin resistance, gut microbiome, liver damage, fibrosis, cirrhosis, HCC.
Abstract: Metabolic-dysfunction-associated steatotic liver disease (MASLD), previously referred
to as nonalcoholic fatty liver disease (NAFLD), affecting approximately 30% of the global population.
Projections suggest that MASLD incidence may rise by up to 56% over the next decade.
MASLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in the USA,
France, UK, and other regions worldwide. The prevalence of MASLD and MASLD-related liver
damage is expected to parallel the increasing rates of obesity and type 2 Diabetes Mellitus (T2DM)
globally. The factors contributing to MASLD development and its progression to metabolic-dysfunction-
associated steatohepatitis (MASH), fibrosis, cirrhosis, and HCC remain poorly understood.
Evidence from cell-based, animal-based, and human-subject studies suggests that insulin
resistance, endoplasmic reticulum stress, oxidative stress, impaired autophagy, genetics, epigenetics,
reduced immune surveillance, increased gut inflammation, and gut dysbiosis are crucial events
in MASLD pathogenesis. In recent years, dysregulation of gut microbiota has emerged as a potential
mechanism implicated in MASLD and MASLD-related hepatocarcinogenesis. This review
briefly outlines the mechanistic events significant for MASLD pathogenesis. Additionally, it offers
insight into dysregulated gut microbiota and its correlation with MASLD and MASLD-related liver
damage. Furthermore, it highlights pertinent questions for cell and microbiologists in the MASLD
research field. It underscores the necessity for identifying factors leading to gut microbiome
dysregulation in MASLD and MASH pathogenesis. Identifying these factors could aid in the development
of novel strategies for managing MASLD and MASLD-related liver damage.
