Miller, Ruth R, Uyaguari-Diaz, Miguel, McCabe, Mark N et al. · PloS one · 2016 · DOI
Researchers used advanced genetic sequencing to search for viruses and bacteria in the blood of people with ME/CFS, comparing them to people with other conditions and healthy individuals. They found very little microbial material in anyone's blood, and the small differences they observed were likely caused by contamination during sample handling rather than actual differences between groups. This study teaches an important lesson: when looking for germs in blood samples, scientists must be extremely careful about how they handle samples and must use proper controls to avoid false conclusions.
This study is important because it demonstrates a critical methodological principle: many previous studies claiming to find specific microbes in ME/CFS blood may have produced false positive results due to contamination and batch effects. Understanding these technical limitations helps researchers design better future studies and prevents the field from pursuing false leads about infectious causes. This work ultimately protects ME/CFS patients by ensuring that future research is built on solid scientific foundations.
This study does not prove that ME/CFS has no infectious cause—it only shows that plasma metagenomic sequencing as currently performed may not be a reliable method for detecting microbes in ME/CFS. The study also does not address whether microbes in other tissues (not blood) might be involved in ME/CFS pathology. The findings do not eliminate infection as a potential contributor, but rather highlight that better technical approaches are needed to investigate it.
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
Miller, Ruth R, Uyaguari-Diaz, Miguel, McCabe, Mark N, Montoya, Vincent, Gardy, Jennifer L, Parker, Shoshana, et al. (2016). Metagenomic Investigation of Plasma in Individuals with ME/CFS Highlights the Importance of Technical Controls to Elucidate Contamination and Batch Effects.. PloS one. https://doi.org/10.1371/journal.pone.0165691
BibTeX
@article{mecfsatlas-miller-2016-metagenomic-investigation,
author = {Miller, Ruth R and Uyaguari-Diaz, Miguel and McCabe, Mark N and Montoya, Vincent and Gardy, Jennifer L and Parker, Shoshana and Steiner, Theodore and Hsiao, William and Nesbitt, Matthew J and Tang, Patrick and Patrick, David M and CCD Study Group},
title = {Metagenomic Investigation of Plasma in Individuals with ME/CFS Highlights the Importance of Technical Controls to Elucidate Contamination and Batch Effects.},
journal = {PloS one},
year = {2016},
doi = {10.1371/journal.pone.0165691},
note = {PubMed: 27806082},
url = {https://www.mecfsatlas.com/evidence/miller-2016-metagenomic-investigation},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/miller-2016-metagenomic-investigation
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