Gut microbiome is associated with multiple sclerosis activity in children

Objective To identify features of the gut microbiome associated with multiple sclerosis activity over time. Methods We used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric‐onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes...

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Vydáno v:Annals of clinical and translational neurology Ročník 8; číslo 9; s. 1867 - 1883
Hlavní autoři: Horton, Mary K., McCauley, Kathryn, Fadrosh, Douglas, Fujimura, Kei, Graves, Jennifer, Ness, Jayne, Wheeler, Yolanda, Gorman, Mark P., Benson, Leslie A., Weinstock‐Guttman, Bianca, Waldman, Amy, Rodriguez, Moses, Tillema, Jan‐Mendelt, Krupp, Lauren, Belman, Anita, Mar, Soe, Rensel, Mary, Chitnis, Tanuja, Casper, Theron Charles, Rose, John, Hart, Janace, Shao, Xiaorong, Tremlett, Helen, Lynch, Susan V., Barcellos, Lisa F., Waubant, Emmanuelle
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States John Wiley & Sons, Inc 01.09.2021
John Wiley and Sons Inc
Wiley
Témata:
Adolescent
Child
Digestive system
Female
Follow-Up Studies
Gastrointestinal Microbiome
Gut microbiota
Humans
Male
Microbiota
Multiple sclerosis
Multiple Sclerosis - microbiology
Multiple Sclerosis - physiopathology
Nervous system
Pediatrics
RNA, Ribosomal, 16S
Taxonomy
United States > US
San Francisco California
California
ISSN:2328-9503, 2328-9503
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Shrnutí:Objective To identify features of the gut microbiome associated with multiple sclerosis activity over time. Methods We 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. Results Participants 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. Interpretation Both 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.
Bibliografie:National Institute of Neurological Disorders and Stroke : F13NS108668 : R01NS071463 National Multiple Sclerosis Society : HC150906233 : RG4861A13
Funding Information
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2328-9503
2328-9503
DOI:10.1002/acn3.51441