Gut microbiome is associated with multiple sclerosis activity in children
Abstract 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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-09-01
|
Series: | Annals of Clinical and Translational Neurology |
Online Access: | https://doi.org/10.1002/acn3.51441 |
id |
doaj-925deb8cc6a2430fb7a92130f9385d69 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mary K. Horton Kathryn McCauley Douglas Fadrosh Kei Fujimura Jennifer Graves Jayne Ness Yolanda Wheeler Mark P. Gorman Leslie A. Benson Bianca Weinstock‐Guttman Amy Waldman Moses Rodriguez Jan‐Mendelt Tillema Lauren Krupp Anita Belman Soe Mar Mary Rensel Tanuja Chitnis Theron Charles Casper John Rose Janace Hart Xiaorong Shao Helen Tremlett Susan V. Lynch Lisa F. Barcellos Emmanuelle Waubant the U.S. Network of Pediatric MS Centers |
spellingShingle |
Mary K. Horton Kathryn McCauley Douglas Fadrosh Kei Fujimura Jennifer Graves Jayne Ness Yolanda Wheeler Mark P. Gorman Leslie A. Benson Bianca Weinstock‐Guttman Amy Waldman Moses Rodriguez Jan‐Mendelt Tillema Lauren Krupp Anita Belman Soe Mar Mary Rensel Tanuja Chitnis Theron Charles Casper John Rose Janace Hart Xiaorong Shao Helen Tremlett Susan V. Lynch Lisa F. Barcellos Emmanuelle Waubant the U.S. Network of Pediatric MS Centers Gut microbiome is associated with multiple sclerosis activity in children Annals of Clinical and Translational Neurology |
author_facet |
Mary K. Horton Kathryn McCauley Douglas Fadrosh Kei Fujimura Jennifer Graves Jayne Ness Yolanda Wheeler Mark P. Gorman Leslie A. Benson Bianca Weinstock‐Guttman Amy Waldman Moses Rodriguez Jan‐Mendelt Tillema Lauren Krupp Anita Belman Soe Mar Mary Rensel Tanuja Chitnis Theron Charles Casper John Rose Janace Hart Xiaorong Shao Helen Tremlett Susan V. Lynch Lisa F. Barcellos Emmanuelle Waubant the U.S. Network of Pediatric MS Centers |
author_sort |
Mary K. Horton |
title |
Gut microbiome is associated with multiple sclerosis activity in children |
title_short |
Gut microbiome is associated with multiple sclerosis activity in children |
title_full |
Gut microbiome is associated with multiple sclerosis activity in children |
title_fullStr |
Gut microbiome is associated with multiple sclerosis activity in children |
title_full_unstemmed |
Gut microbiome is associated with multiple sclerosis activity in children |
title_sort |
gut microbiome is associated with multiple sclerosis activity in children |
publisher |
Wiley |
series |
Annals of Clinical and Translational Neurology |
issn |
2328-9503 |
publishDate |
2021-09-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1002/acn3.51441 |
work_keys_str_mv |
AT marykhorton gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT kathrynmccauley gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT douglasfadrosh gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT keifujimura gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT jennifergraves gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT jayneness gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT yolandawheeler gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT markpgorman gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT leslieabenson gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT biancaweinstockguttman gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT amywaldman gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT mosesrodriguez gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT janmendelttillema gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT laurenkrupp gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT anitabelman gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT soemar gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT maryrensel gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT tanujachitnis gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT theroncharlescasper gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT johnrose gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT janacehart gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT xiaorongshao gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT helentremlett gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT susanvlynch gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT lisafbarcellos gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT emmanuellewaubant gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren AT theusnetworkofpediatricmscenters gutmicrobiomeisassociatedwithmultiplesclerosisactivityinchildren |
_version_ |
1717779955805323264 |
spelling |
doaj-925deb8cc6a2430fb7a92130f9385d692021-09-06T06:03:43ZengWileyAnnals of Clinical and Translational Neurology2328-95032021-09-01891867188310.1002/acn3.51441Gut microbiome is associated with multiple sclerosis activity in childrenMary K. Horton0Kathryn McCauley1Douglas Fadrosh2Kei Fujimura3Jennifer Graves4Jayne Ness5Yolanda Wheeler6Mark P. Gorman7Leslie A. Benson8Bianca Weinstock‐Guttman9Amy Waldman10Moses Rodriguez11Jan‐Mendelt Tillema12Lauren Krupp13Anita Belman14Soe Mar15Mary Rensel16Tanuja Chitnis17Theron Charles Casper18John Rose19Janace Hart20Xiaorong Shao21Helen Tremlett22Susan V. Lynch23Lisa F. Barcellos24Emmanuelle Waubant25the U.S. Network of Pediatric MS CentersDivision of Epidemiology University of California, Berkeley Berkeley California USADepartment of Medicine‐ Gastroenterology University of California, San Francisco San Francisco CaliforniaUSADepartment of Medicine‐ Gastroenterology University of California, San Francisco San Francisco CaliforniaUSADepartment of Medicine‐ Gastroenterology University of California, San Francisco San Francisco CaliforniaUSADepartment of Neurosciences University of California, San Diego La Jolla California USADivision of Pediatric Neurology University of Alabama Birmingham Alabama USADivision of Pediatric Neurology University of Alabama Birmingham Alabama USADepartment of Neurology Boston Children’s Hospital Boston Massachusetts USADepartment of Neurology Boston Children’s Hospital Boston Massachusetts USADepartment of Neurology State University of New York Buffalo New York USADepartment of Neurology Children’s Hospital of Philadelphia Philadelphia Pennsylvania USADepartment of Neurology Mayo Clinic Rochester Minnesota USADepartment of Neurology Mayo Clinic Rochester Minnesota USAPediatric Multiple Sclerosis Center New York University Langone Medical Center New York New York USAPediatric Multiple Sclerosis Center New York University Langone Medical Center New York New York USADepartment of Neurology Washington University in St. Louis St. Louis Missouri USADepartment of Neurology Cleveland Clinic Cleveland Ohio USADivision of Child Neurology Massachusetts General Hospital Boston Massachusetts USASchool of Medicine University of Utah School Salt Lake City Utah USASchool of Medicine University of Utah School Salt Lake City Utah USADepartment of Neurology University of California, San Francisco San Francisco California USADivision of Epidemiology University of California, Berkeley Berkeley California USADepartment of Medicine University of British Columbia Vancouver British Columbia CanadaDepartment of Medicine‐ Gastroenterology University of California, San Francisco San Francisco CaliforniaUSADivision of Epidemiology University of California, Berkeley Berkeley California USADepartment of Neurology University of California, San Francisco San Francisco California USAAbstract 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.https://doi.org/10.1002/acn3.51441 |