Gut microbiota in early pediatric multiple sclerosis: a case-control study
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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 Uniform resource identifier for web resources.
Authors
Tremlett H, Fadrosh DW, Faruqi AA, Zhu F, Hart J, Roalstad S, Graves J, Lynch S, Waubant E
Journal
European journal of neurology
Year
2016
BACKGROUND AND PURPOSE: Alterations in the gut microbial community composition may be influential in neurological disease. Microbial community profiles were compared between early onset pediatric multiple sclerosis (MS) and control children similar for age and sex. METHODS: Children ≤18 years old within 2 years of MS onset or controls without autoimmune disorders attending a University of California, San Francisco, USA, pediatric clinic were examined for fecal bacterial community composition and predicted function by 16S ribosomal RNA sequencing and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. Associations between subject characteristics and the microbiota, including beta diversity and taxa abundance, were identified using non-parametric tests, permutational multivariate analysis of variance and negative binomial regression. RESULTS: Eighteen relapsing-remitting MS cases and 17 controls (mean age 13 years; range 4-18) were studied. Cases had a short disease duration (mean 11 months; range 2-24) and half were immunomodulatory drug (IMD) naïve. Whilst overall gut bacterial beta diversity was not significantly related to MS status, IMD exposure was (Canberra, P < 0.02). However, relative to controls, MS cases had a significant enrichment in relative abundance for members of the Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) and depletion in Lachnospiraceae and Ruminococcaceae (all P and q < 0.000005). Microbial genes predicted as enriched in MS versus controls included those involved in glutathione metabolism (Mann-Whitney, P = 0.017), findings that were consistent regardless of IMD exposure. CONCLUSIONS: In recent onset pediatric MS, perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration. Findings were suggestive of a pro-inflammatory milieu.
Statistical test
Negative Binomial Regression
Experiment 1
Needs review
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- 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
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- multiple sclerosis Disseminated Sclerosis,generalized multiple sclerosis,insular sclerosis,MS,MS (Multiple Sclerosis),multiple sclerosis,MULTIPLE SCLEROSIS ACUTE FULMINATING,Multiple Sclerosis, Acute Fulminating,Sclerosis, Disseminated,Sclerosis, Multiple
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- pediatric multiple sclerosis
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- early pediatric multiple sclerosis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 17
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 2 months
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
- 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
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, ethnic group, breast feeding, sex
Alpha Diversity
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 3a, 3b
Description: Difference between multiple sclerosis and controls in the gut microbial communities
Abundance in Group 1: increased abundance in pediatric multiple sclerosis
| NCBI | Links |
|---|---|
| Bilophila ✕� | |
| Bifidobacterium � | |
| Eubacteriales | |
| Desulfovibrio ✕� | |
| Coriobacteriaceae | |
| Prevotella copri � | |
| Catenibacterium � | |
| Christensenellaceae | |
| Oscillospiraceae | |
| Phascolarctobacterium � |
Revision editor(s): WikiWorks
Signature 2
Needs review
Source: Figure 3a, 3b
Description: Difference between multiple sclerosis and controls in the gut microbial communities
Abundance in Group 1: decreased abundance in pediatric multiple sclerosis
| NCBI | Links |
|---|---|
| Lachnospira � | |
| Oscillospiraceae | |
| Paraprevotella � | |
| Eubacteriales | |
| Prevotella copri � | |
| Bacteroides � | |
| Oscillospira | |
| Peptostreptococcus anaerobius � |
Revision editor(s): WikiWorks
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- IMD naive cases
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- IMD exposure multiple sclerosis cases
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Not specified
- Group 0 sample size Number of subjects in the control (unexposed) group
- 9
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
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
- Not specified
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
Alpha Diversity
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 2b
Description: Difference between multiple sclerosis and controls influenced by the immunomodulatory drug IMD exposure status of cases
Abundance in Group 1: increased abundance in IMD exposure multiple sclerosis cases
| NCBI | Links |
|---|---|
| Actinomycetota |
Revision editor(s): WikiWorks
Signature 2
Needs review
Source: Figure 2b
Description: Difference between multiple sclerosis and controls influenced by the immunomodulatory drug IMD exposure status of cases
Abundance in Group 1: decreased abundance in IMD exposure multiple sclerosis cases
| NCBI | Links |
|---|---|
| Mycoplasmatota | |
| Cyanobacteriota |
Revision editor(s): WikiWorks
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- IMD naive cases multiple sclerosis
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
Lab analysis
Statistical Analysis
Alpha Diversity
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Supplementary Table 7a, Supp Table 7b
Description: Taxa enriched and depleted in the IMD naive cases vs. controls
Abundance in Group 1: increased abundance in IMD naive cases multiple sclerosis
Signature 2
Needs review
Source: Supplementary Table 7a, Supp Table 7b
Description: Taxa enriched and depleted in the IMD naive cases vs. controls
Abundance in Group 1: decreased abundance in IMD naive cases multiple sclerosis
Revision editor(s): WikiWorks
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