Volume 10 Number 1 2026
Integrative Molecular and Microbial Mechanisms Linking Liver Fibrosis, Cancer Biology, and Host-Microbe Interactions
Anwar Ullah 1* Okti Sri Purwanti 2, Agus Sudaryanto 2, Beti Kristinawati 2,
Integrative Biomedical Research 10 (1) 1-8 https://doi.org/10.25163/biomedical.10110621
Submitted: 02 January 2026 Accepted: 27 February 2026 Published: 01 March 2026
The liver rarely fails in isolation. Over the past decade, it has become difficult to discuss hepatic fibrosis without also discussing the gut — the two organs are joined by the portal vein so intimately that disturbances on one side of the circuit are, sooner or later, felt on the other. This review draws together that evidence into a single, admittedly ambitious, narrative: how dysbiosis of the intestinal microbiota initiates a chain of events — barrier breakdown, portal translocation of microbial products, innate immune sensing, hepatic stellate cell (HSC) activation — that culminates not only in fibrosis but, in a meaningful subset of patients, in hepatocellular and gastrointestinal cancers. We trace the anatomical and immunological basis of the gut–liver–immune axis, describe how loss of eubiosis shifts the microbiome toward pro-inflammatory, genotoxin-producing pathobionts, and detail the molecular sensing machinery (TLR4/MyD88/NF-κB, NLRP3/NLRP6) through which translocated pathogen-associated molecular patterns activate Kupffer cells and HSCs. A dedicated section examines a newly described structural-immune node — the Nidogen-1–JAK2/STAT3–interleukin-6 axis — and the phytochemical Carpaine as a case study in how a single molecule can simultaneously rebalance hepatic stellate cell activation, macrophage polarization, and gut microecology. We further synthesize how secondary bile acids, short-chain fatty acids, and bacterial genotoxins (colibactin, cytolethal distending toxin, tilimycin) act as molecular switches connecting chronic inflammation to genomic instability, using Fusobacterium nucleatum as a template for pathobiont-driven oncogenesis. Finally, we appraise the current and emerging therapeutic landscape — from receptor-targeted agents such as resmetirom and semaglutide to microbiota-directed and RNA-based strategies — and argue that durable disease modification will likely require interventions that act across, not within, single cellular compartments. Read together, the evidence suggests the gut–liver–immune axis is not a peripheral curiosity but a central organizing principle of chronic liver disease.
Keywords: Gut–liver axis; Intestinal dysbiosis; Hepatic fibrosis; Hepatic stellate cells; Microbial metabolites; Hepatocellular carcinoma.
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