Gut microbiota and treatment response heterogeneity across pharmacological therapies for MASH
Year: 2026
Type: review
Abstract: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with increasing global prevalence. However, substantial inter-individual variability in therapeutic response remains a major challenge for effective disease management. Although the gut microbiota is well recognized as a key contributor to MASH pathogenesis, its role in shaping pharmacological treatment response remains insufficiently understood and underexplored in clinical contexts. In this Review, we summarize evidence suggesting that gut microbiota-associated metabolites, including bile acids, short-chain fatty acids, sphingolipids, and other microbial products, may contribute to variability in therapeutic response across major pharmacological classes for MASH, including FXR agonists, PPAR agonists, FGF19/FGF21 analogues, thyroid hormone receptor-β agonists, and incretin-based therapies. However, for most therapeutic classes, direct clinical evidence linking microbiota features to inter-individual treatment response remains limited, and much of the mechanistic evidence is derived from preclinical studies. We integrate current evidence into a response-oriented conceptual framework linking microbiome composition and metabolic activity to biological processes relevant to drug efficacy. This framework identifies priorities for the prospective validation of microbiome-derived biomarkers and microbiome-informed patient stratification in MASH.
Source: Frontiers in Pharmacology
Authors: Pingping Yan, Shuheng Cai, Juzhi Xia
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223061851