Evidence map›Paper›PMID 40903540›Full record

Articlenpj metabolic health and disease2025

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Xiaoyu Che, Amit Ranjan, Cheng Guo, Keming Zhang, Rochelle Goldsmith, Susan Levine, Kegan J Moneghetti, Yali Zhai, Liner Ge, Nischay Mishra and 9 more

Abstract read
In one paragraph

Article in npj metabolic health and disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Xiaoyu Che *Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA. xc2273@cumc.columbia.edu.
Amit Ranjan *Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
Cheng GuoCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
Keming ZhangCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
Rochelle GoldsmithDepartment of Medicine, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA.
Susan LevineLevine Clinic, New York, NY, USA.
Kegan J MoneghettiBaker Department of Cardiometabolic Health, University of Melbourne, Parkville, Australia.
Yali ZhaiCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
Liner GeDepartment of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
Nischay MishraCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
Mady HornigThe Feinstein Institutes for Medical Research, Northwell Health, New York, USA.
Lucinda BatemanThe Bateman Horne Center, Salt Lake City, UT, USA.
Nancy G KlimasInstitute for Neuro-Immune Medicine, College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA.
Jose G MontoyaPalo Alto Medical Foundation, Jack S. Remington Laboratory for Specialty Diagnostics of Toxoplasmosis, Palo Alto, CA, USA.
Daniel L PetersonSierra Internal Medicine at Incline Village, Incline Village, NV, USA.
Sabra L KleinJohns Hopkins Center for Women's Health, Sex, and Gender Research, Baltimore, MD, USA.
Oliver FiehnUC Davis Genome Center-Metabolomics, University of California, Davis, CA, USA.
Anthony L KomaroffDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
W Ian LipkinCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA. wil2001@cumc.columbia.edu.

Funding

Project 3 : Clinical correlates and diagnostics in ME/CFSU54AI138370 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LIPKIN, W. IAN · 2017 to 2022
$10.7M
Center for Solutions for ME/CFS U54AI138370NIAID NIH HHS U54 AI138370
6 · The paper itself

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue, post-exertional malaise (PEM), and cognitive dysfunction. ME/CFS patients often report a prodrome consistent with infection. We present a multi-omics analysis based on plasma metabolomic and proteomic profiling, and immune responses to microbial stimulation, before and after exercise. We report evidence of an exaggerated innate immune response after exposure to microbial antigens; impaired energy production involving the citric acid cycle, beta-oxidation of fatty acids, and urea cycle energy production from amino acids; systemic inflammation linked to lipid abnormalities; disrupted extracellular matrix homeostasis with release of endogenous ligands that promote inflammation; reduced cell-cell adhesion and associated gut dysbiosis; complement activation; redox imbalance reflected by disturbances in copper-dependent antioxidant pathways; and dysregulation of tryptophan-serotonin-kynurenine pathways. Many abnormalities were worse following exercise and correlated with the intensity of symptoms. Our findings may inform development of targeted therapeutic interventions for ME/CFS and PEM.

Identifiers

PMID40903540
PMCPMC12408823

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.