Gut microbiota in early pediatric multiple sclerosis: a case-control study

From BugSigDB
Reviewed Marked as Reviewed by Atrayees on 2023-6-30
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
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
Keywords:
16S rRNA, case−control study, gut microbiome, gut microbiota, immunomodulatory drugs, pediatric multiple sclerosis, risk factors
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.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Atrayees, Suwaiba, Victoria

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
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,Multiple sclerosis
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).
raw counts
Statistical test
Negative Binomial Regression
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

Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): WikiWorks

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 Quality ControlLinks
Bilophila
Bifidobacterium
Eubacteriales
Desulfovibrio
Coriobacteriaceae
Segatella copri
Catenibacterium
Christensenellaceae
Oscillospiraceae
Phascolarctobacterium

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): WikiWorks

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 Quality ControlLinks
Lachnospira
Oscillospiraceae
Paraprevotella
Eubacteriales
Segatella copri
Bacteroides
Oscillospira
Peptostreptococcus anaerobius

Revision editor(s): WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Suwaiba, WikiWorks, Atrayees

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
Sclerosis cases influenced by the immunomodulatory drug [IMD] exposure status.
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).
relative abundances
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

Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): WikiWorks

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 Quality ControlLinks
Actinomycetota

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): WikiWorks

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 Quality ControlLinks
Mycoplasmatota
Cyanobacteriota

Revision editor(s): WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Atrayees

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 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
16

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): Lwaldron, WikiWorks

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

NCBI Quality ControlLinks
Acidaminococcus
Akkermansia muciniphila
Atopobium
Bacteroides caccae
Bacteroides ovatus
Bifidobacterium
Bilophila
Blautia producta
Catenibacterium
Christensenellaceae
Comamonadaceae
Coprococcus
Coriobacteriaceae
Desulfovibrio
Dorea
Eubacteriales
Eubacterium
Faecalibacterium prausnitzii
Haemophilus parainfluenzae
Lachnospiraceae
Megamonas
Megasphaera
Methanobrevibacter
Oscillospira
Oscillospiraceae
Parabacteroides distasonis
Phascolarctobacterium
Phocaeicola plebeius
Segatella copri
Leyella stercorea
Pseudoramibacter
Ruminococcus
Sutterella
Veillonella dispar
Mediterraneibacter gnavus

Revision editor(s): Lwaldron, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-6-30

Curated date: 2021/01/10

Curator: Rimsha Azhar

Revision editor(s): WikiWorks

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

NCBI Quality ControlLinks
Oscillospiraceae
Segatella copri
Ligilactobacillus ruminis
Paraprevotella
Lachnospiraceae
Rikenellaceae
Bacteroides
Ruminococcus
Parabacteroides distasonis
Bacteroides uniformis
Butyricimonas
Mitsuokella multacida
Coprococcus
Peptostreptococcus anaerobius
Anaerostipes
Akkermansia muciniphila
Bacteroides eggerthii
Sutterella
Faecalibacterium prausnitzii
Bacteroides fragilis
Catenibacterium
Dialister
Phocaeicola coprophilus
Bacteroides ovatus
Dorea

Revision editor(s): WikiWorks