Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al. · npj metabolic health and disease · 2025 · DOI
This study examined blood samples and immune responses in ME/CFS patients to understand why they experience extreme fatigue and feeling worse after activity. Researchers found that patients' immune systems overreact to germs, their bodies have trouble producing energy efficiently, and they have several chemical imbalances in their blood. These problems got worse after exercise and matched how sick patients felt.
This study identifies potential biological mechanisms underlying ME/CFS and post-exertional malaise, moving beyond dismissing the condition as psychological. The findings could guide development of targeted treatments for specific pathways rather than symptomatic management alone, offering hope for more effective interventions.
This mechanistic study identifies associations between biomarkers and symptoms but does not prove causation—abnormal metabolites may be consequences rather than causes of ME/CFS. The study does not establish whether these findings apply to all ME/CFS patients or explain how the condition initiates in the first place. Exercise-induced worsening of biomarkers requires validation in larger, more diverse populations before clinical application.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Che, Xiaoyu, Ranjan, Amit, Guo, Cheng, Zhang, Keming, Goldsmith, Rochelle, Levine, Susan, et al. (2025). Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.. npj metabolic health and disease. https://doi.org/10.1038/s44324-025-00079-w
BibTeX
@article{mecfsatlas-che-2025-heightened-innate-2,
author = {Che, Xiaoyu and Ranjan, Amit and Guo, Cheng and Zhang, Keming and Goldsmith, Rochelle and Levine, Susan and Moneghetti, Kegan J and Zhai, Yali and Ge, Liner and Mishra, Nischay and Hornig, Mady and Bateman, Lucinda and Klimas, Nancy G and Montoya, Jose G and Peterson, Daniel L and Klein, Sabra L and Fiehn, Oliver and Komaroff, Anthony L and Lipkin, W Ian},
title = {Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.},
journal = {npj metabolic health and disease},
year = {2025},
doi = {10.1038/s44324-025-00079-w},
note = {PubMed: 40903540},
url = {https://www.mecfsatlas.com/evidence/che-2025-heightened-innate-2},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/che-2025-heightened-innate-2
Contribute
Private, reviewed by a human. Not a public comment thread.