{
  "abstract": "Background Some people with multiple sclerosis display changes in their gut microbiota with separate evidence suggesting that symptoms may worsen following a high-fibre diet. We hypothesised that in people with multiple sclerosis whose gut microbiota are less able to efficiently ferment dietary fibres, unfermented β-fructans induce inflammation.Methods Diet data (n=48 individuals with multiple sclerosis, n=78 unaffected controls) and stool microbiome data (n=31 individuals with multiple sclerosis, n=61 unaffected controls) were previously collected from participants. Daily fibre subtype intakes were calculated and compared with faecal shotgun metagenomic sequencing in paediatric onset multiple sclerosis and unaffected persons. Response to unfermented β-fructans was examined in a germ-free experimental autoimmune encephalomyelitis (EAE) mouse model (unable to ferment fibres). Mice were fed β-fructans or control fibre diet beginning at symptom onset (day 14). EAE scores and weights were recorded daily. Intestinal and central nervous system tissues were collected at two endpoints to examine inflammatory responses and demyelinating lesions.Results Individuals with paediatric onset multiple sclerosis consumed less β-fructans (2.4 g/day±0.3 SD; p<0.05) than unaffected participants (3.6 g/day±0.4), which coincided with differences in the gut microbiota including lower fibre fermenting enzymes. Mice exposed to unfermented β-fructans sustained worsened EAE symptoms (day 20–28; p<0.05), immune activation in the gut and immune activation plus demyelinating lesions in the spinal cord compared with mice on control diet.Conclusions The gut microbiota of individuals with paediatric-onset multiple sclerosis showed reduced fibre fermenting properties, and our animal findings suggest that unfermented β-fructans can worsen demyelination and promote gut–brain axis immune activation. Lower β-fructan consumption was observed among participants with paediatric-onset multiple sclerosis. Future longitudinal studies are warranted to confirm the findings uncovered in this manuscript.",
  "authors": [
    {
      "affiliations": [
        "Agriculture, Food and Nutrition Sciences Department, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Stephanie L Tollenaar"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Reihane Khorasaniha"
    },
    {
      "affiliations": [
        "Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada"
      ],
      "name": "Juan Jovel"
    },
    {
      "affiliations": [
        "Department of Statistical Sciences, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "Ismaila Ba"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Athalia Voisin"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Richard Miller"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Hana Olof"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Ramsha Mahmood"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada",
        "Departments of Medicine and Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada"
      ],
      "name": "Ruth Ann Marrie"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Erin Strachan"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Luisa P Soares"
    },
    {
      "affiliations": [
        "Department of Medicine, University of Alberta, Edmonton, Alberta, Canada",
        "Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Christopher Cheng"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada",
        "Department of Medicine, University of Alberta, Edmonton, Alberta, Canada",
        "Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Jonathan Janveaux"
    },
    {
      "affiliations": [
        "Department of Medicine, University of Alberta, Edmonton, Alberta, Canada",
        "Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Deenaz Zaidi"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Charles N Bernstein"
    },
    {
      "affiliations": [
        "Public Health Agency of Canada, Winnipeg, Manitoba, Canada"
      ],
      "name": "Christine Bonner"
    },
    {
      "affiliations": [
        "Center for NeuroInflammation and Experimental Therapeutics and Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA"
      ],
      "name": "Amit Bar-Or"
    },
    {
      "affiliations": [
        "Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA"
      ],
      "name": "Emmanuelle Waubant"
    },
    {
      "affiliations": [
        "Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada"
      ],
      "name": "E Ann Yeh"
    },
    {
      "affiliations": [
        "Public Health Agency of Canada, Winnipeg, Manitoba, Canada"
      ],
      "name": "Morag Graham"
    },
    {
      "affiliations": [
        "Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada"
      ],
      "name": "Douglas L Arnold"
    },
    {
      "affiliations": [
        "Cleveland Clinic, Cleveland, Ohio, USA"
      ],
      "name": "Julia O’Mahony"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA"
      ],
      "name": "Brenda L Banwell"
    },
    {
      "affiliations": [
        "Department of Neurology, The University of British Columbia, Vancouver, British Columbia, Canada",
        "Djavad Mowafaghian Centre for Brain Health, Vancouver, British Columbia, Canada"
      ],
      "name": "Feng Zhu"
    },
    {
      "affiliations": [
        "Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada"
      ],
      "name": "Ali I Mirza"
    },
    {
      "affiliations": [
        "Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Soheila Karimi-Abdolrezaee"
    },
    {
      "affiliations": [
        "Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Sue Tsai"
    },
    {
      "affiliations": [
        "Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada"
      ],
      "name": "Helen Tremlett"
    },
    {
      "affiliations": [
        "Department of Statistics, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Kevin McGregor"
    },
    {
      "affiliations": [
        "Agriculture, Food and Nutrition Sciences Department, University of Alberta, Edmonton, Alberta, Canada",
        "Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Benjamin P Willing"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada",
        "Department of Medicine, University of Alberta, Edmonton, Alberta, Canada",
        "Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Heather Armstrong"
    }
  ],
  "title": "Reduced fibre-fermenting capacity of gut microbes in multiple sclerosis may result in prebiotic dietary fibre β-fructan promoting inflammation and CNS damage",
  "uid": "b4631602-30c7-5b9a-bb76-8185100989b0"
}