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Abstract Details

The Gut Microbiome in Pediatric-onset Acquired Demyelinating Syndromes by Myelin Oligodendrocyte Glycoprotein Antibody Status
Multiple Sclerosis
P3 - Poster Session 3 (5:00 PM-6:00 PM)
20-008
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).
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.
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.

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.

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.

Authors/Disclosures
Wendy Tsai, MD
PRESENTER
Dr. Tsai has nothing to disclose.
FENG ZHU, MSc Mr. ZHU has nothing to disclose.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania) Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Charles N. Bernstein, MD Dr. Bernstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie, Eli Lilly, Celltrion, Fresenius-Kabi, Janssen, Ferring, Organon, Pfizer, Takeda,. Dr. Bernstein has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie, Eli Lilly, Janssen, Fresenius Kabi, Medtronic,Pfizer, Takeda. The institution of Dr. Bernstein has received research support from Abbvie, Janssen, Pfizer, Celltrion.
Christine Bonner Miss Bonner has nothing to disclose.
Morag Graham, PhD Dr. Graham has nothing to disclose.
Ruth-Ann Marrie, MD, PhD (University of Manitoba) The institution of Dr. Marrie has received research support from CIHR. The institution of Dr. Marrie has received research support from MS Canada. The institution of Dr. Marrie has received research support from National MS Society. The institution of Dr. Marrie has received research support from Crohn's and Colitis Canada. The institution of Dr. Marrie has received research support from US Department of Defense. The institution of Dr. Marrie has received research support from The Arthritis Society. The institution of Dr. Marrie has received research support from CMSC.
Ali Mirza, PhD Dr. Mirza has nothing to disclose.
Julia O'Mahony (The Hospital for Sick Children) Ms. O'Mahony has nothing to disclose.
E. Ann Yeh, MD, MA, FRCPC (Hospital for Sick Children) Dr. Yeh has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pipeline therapeutics. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Yeh has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for SCN. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Yeh has received research support from CIHR. The institution of Dr. Yeh has received research support from National MS Society. The institution of Dr. Yeh has received research support from SickKids Foundation. The institution of Dr. Yeh has received research support from MSSC. The institution of Dr. Yeh has received research support from Garry Hurvitz Foundation. The institution of Dr. Yeh has received research support from Leong Centre. The institution of Dr. Yeh has received research support from OMSLife. The institution of Dr. Yeh has received research support from Canada's Drug Agency. Dr. Yeh has received personal compensation in the range of $0-$499 for serving as a Author with Medscape. Dr. Yeh has a non-compensated relationship as a Editorial Board with Neurology that is relevant to AAN interests or activities. Dr. Yeh has a non-compensated relationship as a Editorial Board with MSJ that is relevant to AAN interests or activities.
Brenda L. Banwell, MD, FAAN (Johns Hopkins University) Dr. Banwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Banwell has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Banwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Banwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Banwell has received research support from National MS Society. The institution of Dr. Banwell has received research support from NIH.
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center) The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.
Helen Tremlett, PhD, BPharm (University of British Columbia) Dr. Tremlett has nothing to disclose.