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Ann Clin Transl Neurol. 2021 Dec;8(12):2252-2269. doi: 10.1002/acn3.51476. Epub 2021 Dec 09.

The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes.

Annals of clinical and translational neurology

Helen Tremlett, Feng Zhu, Douglas Arnold, Amit Bar-Or, Charles N Bernstein, Christine Bonner, Jessica D Forbes, Morag Graham, Janace Hart, Natalie C Knox, Ruth Ann Marrie, Ali I Mirza, Julia O'Mahony, Gary Van Domselaar, E Ann Yeh, Yinshan Zhao, Brenda Banwell, Emmanuelle Waubant,

Affiliations

  1. Medicine (Neurology), University of British Columbia and The Djavad Mowafaghian Centre for Brain Health, Vancouver, BC, V6T 1Z3, Canada.
  2. The Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
  3. Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perleman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
  4. Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, R3E 3P4, Canada.
  5. National Microbiology Laboratory, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2, Canada.
  6. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
  7. Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, Winnipeg, Manitoba, R3E 0J9, Canada.
  8. Department of Neurology, University of California San Francisco, San Francisco, California, 94158, USA.
  9. Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, Winnipeg, Manitoba, R3A 1R9, Canada.
  10. The Hospital for Sick Children, University of Toronto, Toronto, Ontario, M5G 1X8, Canada.
  11. Division of Neurology, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.

PMID: 34889081 DOI: 10.1002/acn3.51476

Abstract

OBJECTIVE: To examine the gut microbiota in individuals with and without pediatric-onset multiple sclerosis (MS).

METHODS: We compared stool-derived microbiota of Canadian Pediatric Demyelinating Disease Network study participants ≤21 years old, with MS (disease-modifying drug [DMD] exposed and naïve) or monophasic acquired demyelinating syndrome [monoADS] (symptom onset <18 years), and unaffected controls. All were ≥30 days without antibiotics or corticosteroids. V4 region 16S RNA gene-derived amplicon sequence variants (Illumina MiSeq) were assessed using negative binomial regression and network analyses; rate ratios were age- and sex-adjusted (aRR).

RESULTS: Thirty-two MS, 41 monoADS (symptom onset [mean] = 14.0 and 6.9 years) and 36 control participants were included; 75%/56%/58% were female, with mean ages at stool sample = 16.5/13.8/15.1 years, respectively. Nine MS cases (28%) were DMD-naïve. Although microbiota diversity (alpha, beta) did not differ between participants (p > 0.1), taxa-level and gut community networks did. MS (vs. monoADS) exhibited > fourfold higher relative abundance of the superphylum Patescibacteria (aRR = 4.2;95%CI:1.6-11.2, p = 0.004, Q = 0.01), and lower abundances of short-chain fatty acid (SCFA)-producing Lachnospiraceae (Anaerosporobacter) and Ruminococcaceae (p, Q < 0.05). DMD-naïve MS cases were depleted for Clostridiales vadin-BB60 (unnamed species) versus either DMD-exposed, controls (p, Q < 0.01), or monoADS (p = 0.001, Q = 0.06) and exhibited altered community connectedness (p < 10

INTERPRETATION: Gut microbiota community structure, function and connectivity, and not just individual taxa, are of likely importance in MS.

© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

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