Evidence map›Paper›PMID 34409759›Full record

ArticleAnnals of clinical and translational neurology2021

Gut microbiome is associated with multiple sclerosis activity in children.

Mary K Horton, Kathryn McCauley, Douglas Fadrosh, Kei Fujimura, Jennifer Graves, Jayne Ness, Yolanda Wheeler, Mark P Gorman, Leslie A Benson, Bianca Weinstock-Guttman and 17 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
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  7. Specific microbial ratio in the gut microbiome is associated with multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  9. Observational
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  20. Frontiers in immunology · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 14 institutions in 2 countries.

Mary K HortonDivision of Epidemiology, University of California, Berkeley, Berkeley, California, USA.ORCID 0000-0002-0854-4219
Kathryn McCauleyDepartment of Medicine- Gastroenterology, University of California, San Francisco, San Francisco, California, USA.
Douglas FadroshDepartment of Medicine- Gastroenterology, University of California, San Francisco, San Francisco, California, USA.
Kei FujimuraDepartment of Medicine- Gastroenterology, University of California, San Francisco, San Francisco, California, USA.
Jennifer GravesDepartment of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Jayne NessDivision of Pediatric Neurology, University of Alabama, Birmingham, Alabama, USA.
Yolanda WheelerDivision of Pediatric Neurology, University of Alabama, Birmingham, Alabama, USA.
Mark P GormanDepartment of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
Leslie A BensonDepartment of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
Bianca Weinstock-GuttmanDepartment of Neurology, State University of New York, Buffalo, New York, USA.
Amy WaldmanDepartment of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Moses RodriguezDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Jan-Mendelt TillemaDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Lauren KruppPediatric Multiple Sclerosis Center, New York University Langone Medical Center, New York, New York, USA.
Anita BelmanPediatric Multiple Sclerosis Center, New York University Langone Medical Center, New York, New York, USA.
Soe MarDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Mary RenselDepartment of Neurology, Cleveland Clinic, Cleveland, Ohio, USA.
Tanuja ChitnisDivision of Child Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-9897-4422
Theron Charles CasperSchool of Medicine, University of Utah School, Salt Lake City, Utah, USA.
John RoseSchool of Medicine, University of Utah School, Salt Lake City, Utah, USA.
Janace HartDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Xiaorong ShaoDivision of Epidemiology, University of California, Berkeley, Berkeley, California, USA.
Helen TremlettDepartment of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.ORCID 0000-0001-5804-2535
Susan V LynchDepartment of Medicine- Gastroenterology, University of California, San Francisco, San Francisco, California, USA.
Lisa F BarcellosDivision of Epidemiology, University of California, Berkeley, Berkeley, California, USA.
Emmanuelle WaubantDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0001-5188-0157
U.S. Network of Pediatric MS Centers
University of California, San Francisco · USUniversity of California, Berkeley · USBoston Children's Hospital · USMayo Clinic · USNYU Langone Health · USUniversity of Alabama · USUniversity of Utah · USChildren's Hospital of Philadelphia · USCleveland Clinic · USMassachusetts General Hospital · USUniversity at Buffalo, State University of New York · USUniversity of British Columbia · CAUniversity of California San Diego · USWashington University in St. Louis · US

Funding

Environmental and genetic risk factors for pediatric MSR01NS071463 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WAUBANT, EMMANUELLE LAURENCE · 2010 to 2015
$2.8M
Childhood stress and multiple sclerosis: implications on risk and clinical outcomesF31NS108668 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI HORTON, MARY · 2018 to 2020
$121k
National Multiple Sclerosis Society HC150906233National Multiple Sclerosis Society RG4861A13NINDS NIH HHS F13NS108668NINDS NIH HHS F31 NS108668NINDS NIH HHS R01 NS071463NINDS NIH HHS R01NS071463
6 · The paper itself

Abstract

objectiveTo identify features of the gut microbiome associated with multiple sclerosis activity over time.

methodsWe used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric-onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes and networks identified from weighted genetic correlation network analyses. Prentice-Williams-Peterson Cox proportional hazards models estimated the associations between features and three disease activity outcomes: clinical relapses and both new/enlarging T2 lesions and new gadolinium-enhancing lesions on brain MRI. Analyses were adjusted for age, sex, and disease-modifying therapies.

resultsParticipants were followed, on average, 2.1 years. Five microbes were nominally associated with all three disease activity outcomes after multiple testing correction. These included butyrate producers Odoribacter (relapse hazard ratio = 0.46, 95% confidence interval: 0.24, 0.88) and Butyricicoccus (relapse hazard ratio = 0.49, 95% confidence interval: 0.28, 0.88). Two networks of co-occurring gut microbes were significantly associated with a higher hazard of both MRI outcomes (gadolinium-enhancing lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.29 (1.08, 1.54) and 1.42 (1.18, 1.71), respectively; T2 lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.34 (1.15, 1.56) and 1.41 (1.21, 1.64), respectively). Metagenomic predictions of these networks demonstrated enrichment for amino acid biosynthesis pathways.

interpretationBoth individual and networks of gut microbes were associated with longitudinal multiple sclerosis activity. Known functions and metagenomic predictions of these microbes suggest the important role of butyrate and amino acid biosynthesis pathways. This provides strong support for future development of personalized microbiome interventions to modify multiple sclerosis disease activity.

Indexed as

Gastrointestinal MicrobiomeAdolescentChildFemaleFollow-Up StudiesHumansMaleMultiple SclerosisRNA, Ribosomal, 16SRNA, Ribosomal, 16S

Identifiers

PMID34409759
PMCPMC8419410
OpenAlexW3194279396

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.