Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Nagy-Szakal D, Williams BL, Mishra N, Che X, Lee B, Bateman L, Klimas NG, Komaroff AL, Levine S, Montoya JG, Peterson DL, Ramanan D, Jain K, Eddy ML, Hornig M, Lipkin WI
Journal
Microbiome
Year
2017
Keywords:
Chronic fatigue syndrome, Irritable bowel syndrome, Metabolic pathway, Metagenomic, Microbiota-gut-brain axis, Myalgic encephalomyelitis, Topological data analysis
BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. RESULTS: Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. CONCLUSIONS: Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
Experiment 1
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Chronic fatigue syndrome CFS,chronic fatigue syndrome,myalgic encephalitis,myalgic encephalomeyelitis/chronic fatigue syndrome,Myalgic Encephalomyelitis,myalgic encephalomyelitis,Postviral fatigue syndrome,systemic exertion intolerance disease,Chronic fatigue syndrome
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CFS/ME patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Cases met the 1994 CDC Fukuda and the 2003 Canadian consensus criteria for ME/CFS
- Group 0 sample size Number of subjects in the control (unexposed) group
- 50
- Group 1 sample size Number of subjects in the case (exposed) group
- 50
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 3 months for controls only
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.2
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
- Matched on Factors on which subjects have been matched on in a case-control study
- age, ethnic group, geographic area, sex
Signature 1
Reviewed Marked as Reviewed by Fatima on 2021/07/28
Source: Figure 3a
Description: Differentiately abundant mictobiota between CFS/ME and healthy controls
Abundance in Group 1: increased abundance in CFS/ME patients
Signature 2
Reviewed Marked as Reviewed by Fatima on 2021/07/28
Source: Figure 3a
Description: Differentiately abundant mictobiota between CFS/ME and healthy controls
Abundance in Group 1: decreased abundance in CFS/ME patients
Experiment 2
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CFS/ME patients with IBS
- Group 1 sample size Number of subjects in the case (exposed) group
- 21
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex, ethnic group, geographic area
Signature 1
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Source: Figure 3b
Description: Differentiately abundant mictobiota between CFS/ME with IBS and healthy controls
Abundance in Group 1: increased abundance in CFS/ME patients with IBS
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerostipes caccae | ||
| Clostridium | ||
| Clostridiaceae | ||
| Enterocloster bolteae | ||
| Anaerostipes |
Revision editor(s): WikiWorks
Signature 2
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Source: Figure 3b
Description: Differentiately abundant mictobiota between CFS/ME with IBS and healthy controls
Abundance in Group 1: decreased abundance in CFS/ME patients with IBS
Experiment 3
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CFS/ME patients without IBS
- Group 1 sample size Number of subjects in the case (exposed) group
- 29
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Fatima on 2021/07/28
Source: Figure 3c
Description: Differentiately abundant mictobiota between CFS/ME without IBS and healthy controls
Abundance in Group 1: increased abundance in CFS/ME patients without IBS
Signature 2
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Source: Figure 3c
Description: Differentiately abundant mictobiota between CFS/ME without IBS and healthy controls
Abundance in Group 1: decreased abundance in CFS/ME patients without IBS
| NCBI | Quality Control | Links |
|---|---|---|
| Coprococcus catus | ||
| Parabacteroides distasonis | ||
| Dorea formicigenerans | ||
| Dorea |
Revision editor(s): WikiWorks
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