Gut microbiota and treatment response heterogeneity across pharmacological therapies for MASH
- 1Department of Gastroenterology, Zhaotong First People’s Hospital
- 2Department of Orthopedics, Zhaotong First People’s Hospital
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.
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BibTeX
@article{yan2026microbiota,
title = {{Gut microbiota and treatment response heterogeneity across pharmacological therapies for MASH}},
author = {Pingping Yan and Shuheng Cai and Juzhi Xia},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1968956},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1968956/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gut microbiota and treatment response heterogeneity across pharmacological therapies for MASH
AU - Pingping Yan
AU - Shuheng Cai
AU - Juzhi Xia
PY - 2026
DA - 2026/10/20
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1968956
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1968956/full
AB - 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.
SN - 1663-9812
ER -