Reduced fibre-fermenting capacity of gut microbes in multiple sclerosis may result in prebiotic dietary fibre β-fructan promoting inflammation and CNS damage

Stephanie L Tollenaar; Reihane Khorasaniha; Juan Jovel; Ismaila Ba; Athalia Voisin; Richard Miller; Hana Olof; Ramsha Mahmood; Ruth Ann Marrie; Erin Strachan; Luisa P Soares; Christopher Cheng; Jonathan Janveaux; Deenaz Zaidi; Charles N Bernstein; Christine Bonner; Amit Bar-Or; Emmanuelle Waubant; E Ann Yeh; Morag Graham; Douglas L Arnold; Julia O'Mahony; Brenda L Banwell; Feng Zhu; Ali I Mirza; Soheila Karimi-Abdolrezaee; Sue Tsai; Helen Tremlett; Kevin McGregor; Benjamin P Willing; Heather Armstrong

doi:10.1136/egastro-2025-100296

Reduced fibre-fermenting capacity of gut microbes in multiple sclerosis may result in prebiotic dietary fibre β-fructan promoting inflammation and CNS damage

eGastroenterology. 2026 Jan 22;4(1):e100296. doi: 10.1136/egastro-2025-100296. eCollection 2026.

Authors

Stephanie L Tollenaar^#¹, Reihane Khorasaniha^#², Juan Jovel³, Ismaila Ba⁴, Athalia Voisin², Richard Miller², Hana Olof², Ramsha Mahmood², Ruth Ann Marrie^{2

5}, Erin Strachan⁶, Luisa P Soares⁶, Christopher Cheng^{7

8}, Jonathan Janveaux^{2

7

8}, Deenaz Zaidi^{7

8}, Charles N Bernstein², Christine Bonner⁹, Amit Bar-Or¹⁰, Emmanuelle Waubant¹¹, E Ann Yeh¹², Morag Graham⁹, Douglas L Arnold¹³, Julia O'Mahony¹⁴, Brenda L Banwell¹⁵, Feng Zhu^{16

17}, Ali I Mirza¹⁸, Soheila Karimi-Abdolrezaee¹⁹, Sue Tsai⁶, Helen Tremlett¹⁸, Kevin McGregor²⁰, Benjamin P Willing^{1

8}, Heather Armstrong^{2

7

8}

Affiliations

¹ Agriculture, Food and Nutrition Sciences Department, University of Alberta, Edmonton, Alberta, Canada.
² Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
³ Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
⁴ Department of Statistical Sciences, University of Toronto, Toronto, Ontario, Canada.
⁵ Departments of Medicine and Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada.
⁶ Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
⁷ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
⁸ Centre of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR), University of Alberta, Edmonton, Alberta, Canada.
⁹ Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
¹⁰ Center for NeuroInflammation and Experimental Therapeutics and Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹¹ Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
¹² Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
¹³ Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
¹⁴ Cleveland Clinic, Cleveland, Ohio, USA.
¹⁵ Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁶ Department of Neurology, The University of British Columbia, Vancouver, British Columbia, Canada.
¹⁷ Djavad Mowafaghian Centre for Brain Health, Vancouver, British Columbia, Canada.
¹⁸ Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
¹⁹ Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
²⁰ Department of Statistics, University of Manitoba, Winnipeg, Manitoba, Canada.

^# Contributed equally.

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.

Keywords: Brain-Gut Axis; Dietary Fibre; Encephalomyelitis, Autoimmune, Experimental; Gastrointestinal Microbiome; Multiple Sclerosis.