title: Gut microbiota in early pediatric multiple sclerosis: a case-control study.
abstract: OBJECTIVE
  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.
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
authors.affiliation: University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Fadrosh
authors.affiliation: University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Faruqi
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Janace
authors.initials: J
authors.lastname: Hart
authors.affiliation: University of Utah, Salt Lake City, UT, United States.
authors.forename: Shelly
authors.initials: S
authors.lastname: Roalstad
authors.affiliation: University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Graves
authors.affiliation: University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Lynch
authors.affiliation: University of California, San Francisco, San Francisco, CA, United States.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000382:microbiology*; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S
chemical_list: D012336:RNA, Ribosomal, 16S
keywords: 16S rRNA; case−control study; gut microbiome; gut microbiota; immunomodulatory drugs; pediatric multiple sclerosis; risk factors