Medicinal plant-derived bioactive compounds modulate gut microbiota–host signaling in cancer-related fatigue: a phenotype-to-target framework
- 1State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, National Chinmedomics Research Center, College of Pharmacy, Heilongjiang University of Chinese Medicine
- 2Shandong Key Laboratory of Gelatine Medicines Research and Development, Dong’e Ejiao Co., Ltd.
Abstract
Cancer-related fatigue (CRF) is a frequent and disabling symptom during cancer and anticancer therapy, and pathway-directed pharmacological treatment remains limited. This review examines CRF through the plant–microbiota–host axis, in which medicinal plant-derived bioactive compounds reshape gut microbial community structure and function and are in turn biotransformed by gut microbes into metabolites that host sensors detect. Tumor- and treatment-associated injury of the intestinal mucosa alters epithelial renewal, barrier selectivity, and microbial metabolism, reshaping host exposure to microbial products and metabolites. These changes generate molecular mediators, including short-chain fatty acids, tryptophan-derived metabolites, bile acids, and microbe-associated molecular patterns, which are detected by epithelial, immune, enteroendocrine, and neural sensors. We organize the evidence into mediator–sensor modules and discuss how vagal, humoral, and immune–metabolic routes may converge on brainstem and monoaminergic networks involved in activity, effort, and interoceptive malaise. Because direct causal evidence in CRF remains incomplete, we separate established biology from candidate mechanisms and define pharmacodynamic readouts that can test target engagement. Medicinal plant-derived compounds enter the framework upstream: their microbial conversion products engage the same mediator–sensor modules. We argue that future CRF studies should match the fatigue domain, biological subgroup, molecular target, and biomarker before efficacy is interpreted mechanistically; for plant-derived interventions, this matching must also include the administered compound and its microbially generated metabolites.
Related
- Editorial: Biosynthetic pathways and metabolic engineering of bioactive natural products from medicinal plants
- Special Issue “Plant-Sourced Functional and Bioactive Compounds—Nature’s Blueprint for Improving Human Well-Being”
- New Advances in Bioactive Compounds in Health and Disease: From Molecular Mechanisms to Translational Perspectives
- Natural Bioactive Compounds in Cosmeceuticals: Challenges and Future Perspectives
- Natural Bioactive Compounds Targeting Gut Barrier Integrity and Metabolic Endotoxemia in Cardiometabolic Disease: Mechanistic Insights and Translational Perspectives
BibTeX
@article{jiao2026medicinal,
title = {{Medicinal plant-derived bioactive compounds modulate gut microbiota–host signaling in cancer-related fatigue: a phenotype-to-target framework}},
author = {Yu Jiao and Qin Feng and Yifan Ren and Jinni Sun and Ruyu Wu and Qingchuan Li and Jingzhe Gao and Zhengcan Zhou and Qi Qiu and Zhigang Wang and Kunshuang Shen and Ning Zhang and Liang Zheng and Hui Sun},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1988968},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1988968/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Medicinal plant-derived bioactive compounds modulate gut microbiota–host signaling in cancer-related fatigue: a phenotype-to-target framework
AU - Yu Jiao
AU - Qin Feng
AU - Yifan Ren
AU - Jinni Sun
AU - Ruyu Wu
AU - Qingchuan Li
AU - Jingzhe Gao
AU - Zhengcan Zhou
AU - Qi Qiu
AU - Zhigang Wang
AU - Kunshuang Shen
AU - Ning Zhang
AU - Liang Zheng
AU - Hui Sun
PY - 2026
DA - 2026/10/23
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1988968
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1988968/full
AB - Cancer-related fatigue (CRF) is a frequent and disabling symptom during cancer and anticancer therapy, and pathway-directed pharmacological treatment remains limited. This review examines CRF through the plant–microbiota–host axis, in which medicinal plant-derived bioactive compounds reshape gut microbial community structure and function and are in turn biotransformed by gut microbes into metabolites that host sensors detect. Tumor- and treatment-associated injury of the intestinal mucosa alters epithelial renewal, barrier selectivity, and microbial metabolism, reshaping host exposure to microbial products and metabolites. These changes generate molecular mediators, including short-chain fatty acids, tryptophan-derived metabolites, bile acids, and microbe-associated molecular patterns, which are detected by epithelial, immune, enteroendocrine, and neural sensors. We organize the evidence into mediator–sensor modules and discuss how vagal, humoral, and immune–metabolic routes may converge on brainstem and monoaminergic networks involved in activity, effort, and interoceptive malaise. Because direct causal evidence in CRF remains incomplete, we separate established biology from candidate mechanisms and define pharmacodynamic readouts that can test target engagement. Medicinal plant-derived compounds enter the framework upstream: their microbial conversion products engage the same mediator–sensor modules. We argue that future CRF studies should match the fatigue domain, biological subgroup, molecular target, and biomarker before efficacy is interpreted mechanistically; for plant-derived interventions, this matching must also include the administered compound and its microbially generated metabolites.
SN - 1664-302X
ER -