The Gut Microbiome in Pediatric-onset Acquired Demyelinating Syndromes by Myelin Oligodendrocyte Glycoprotein Antibody Status
Wendy Tsai1, Feng Zhu2, Amit Bar-Or3, Charles Bernstein4, Christine Bonner5, Morag Graham5, Ruth-Ann Marrie6, Ali Mirza2, Julia O'Mahony7, E. Ann Yeh8, Brenda Banwell9, Emmanuelle Waubant10, Helen Tremlett2
1Division of Neurology, University of Toronto, 2Faculty of Medicine (Neurology), University of British Columbia and the Djavad Mowafaghian Centre for Brain Health, 3Center for Neuroinflammation and Experimental Therapeutics and the Department of Neurology, University of Pennsylvania, 4Department of Medicine and Inflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, 5National Microbiology Laboratory, Public Health Agency of Canada, 6Departments of Medicine and Community Health and Epidemiology, Dalhousie University, 7Mellen Center for Multiple Sclerosis, Department of Neurology, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 8Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, 9Department of Pediatrics, Johns Hopkins University, 10Department of Neurology, University of California San Francisco
Objective:
To assess gut microbiome composition differences between myelin oligodendrocyte glycoprotein antibody-positive (MOG+) and antibody-negative (MOG-) children/youth with pediatric-onset acquired demyelinating syndromes (ADS).
Background:
The gut microbiome may play an important role in CNS inflammation. However, little is known about the gut microbiome in pediatric-onset ADS beyond multiple sclerosis (MS). MOG antibody-associated disease is a subset of pediatric-onset ADS defined by antibody-mediated demyelination, with antibodies present in approximately one-third of pediatric-onset ADS cases.
Design/Methods:
Stool samples from the Canadian Pediatric Demyelinating Disease Network study (2015-2018) participants ≤21 years at study enrollment with one or more episodes of non-MS, non-neuromyelitis optica demyelination attacks (onset <18 years) were included. All were antibiotic/corticosteroid-free within 30 days pre-stool sample and tested for serum MOG-IgG antibodies within 30 days of first attack. DNA was extracted, amplified, sequenced, and clustered into amplicon sequence variants. Alpha- and beta-diversity were assessed using Mann-Whitney U test and permutational multivariate analysis of variance, and relative abundance at phylum/genus levels with age- and sex-adjusted negative binomial models.
Results:
Forty-six persons with pediatric-onset ADS (18 MOG+/28 MOG-) were included. The mean age at stool sampling was 14.7 (SD:3.3) years for MOG+ and 17.2 (SD:5.5) years for MOG- participants. MOG+ participants were younger at symptom onset (mean=5.3 years) than MOG- (mean=8.5 years). Alpha- and beta-diversity did not differ between MOG+/MOG- participants (all p>0.3). The relative abundance of phylum Proteobacteria (adjusted-rate ratio [aRR]:0.22; 95% confidence interval [CI]:0.07-0.69; q=0.03) and genus Escherichia/Shigella (aRR:0.01; 95%CI:0.001-0.07; q=0.001) were lower in MOG+ versus MOG- participants.
Conclusions:
While alpha- and beta-diversity did not differ between MOG+/MOG- pediatric-onset ADS, taxa-level differences were observed. Consistent with reports from the wider pediatric-onset ADS literature, our findings suggest that gut microbes differ within the pediatric-onset ADS population and may be influenced by MOG serostatus. Future work incorporating larger cohorts, functional gut microbiome evaluation, and longitudinal follow-up is needed.
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