Gut Microbiota, Oxidative Stress, and Inflammation: Pathophysiological Crosstalk in MASLD, MASH, and Hepatocellular Carcinoma

Davide Nilo^1,*, Giovanni di Lorenzo¹, Marco La Montagna¹, Riccardo Nevola², Aldo Marrone¹, Ferdinando Carlo Sasso¹, Alfredo Caturano³
1 Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
2 Liver Unit, AORN S.G. Moscati, “A. Landolfi” Hospital, Solofra, Avellino, Italy
3 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma University, Rome, Italy
* Corresponding Author: Davide Nilo. Email: email
(This article belongs to the Special Issue: Cellular and Molecular Mechanisms of Gut Microbiota, Oxidative Stress, and Inflammation in Health and Disease)

BIOCELL https://doi.org/10.32604/biocell.2026.081324

Received 28 February 2026; Accepted 08 May 2026; Published online 25 May 2026

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Abstract

Metabolically–dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is increasingly recognized as a systemic disorder at the intersection of metabolic dysregulation, inflammation, and carcinogenesis. Progression from simple steatosis to metabolic dysfunction–associated steatohepatitis (MASH), fibrosis, and hepatocellular carcinoma (HCC) reflects the interplay between metabolic overload, oxidative stress, immune activation, and gut microbiota dysbiosis. In this review, we propose the Redox–Microbiota–Inflammatory Axis as an integrative framework linking metabolic stress to fibrogenesis and hepatocarcinogenesis. Nutrient excess and insulin resistance promote mitochondrial dysfunction and reactive oxygen species (ROS) generation, which activate redox-sensitive inflammatory pathways. Concurrently, gut-derived microbial products and metabolites enhance hepatic immune signaling through the gut–liver axis, creating a self-amplifying pathogenic loop. Understanding this interconnected network highlights biologically actionable pathways and supports emerging therapeutic strategies targeting oxidative stress, inflammation, and microbiota-driven mechanisms across the MASLD spectrum.