Gut microbiota dysfunction may turn prebiotic fibre harmful in multiple sclerosis
image: (A) Dietary fibre subtypes including β-fructan (FOS, inulin), pectin and AX were assessed using diet data from individuals with paediatric onset MS (n=48) and unaffected controls (n=78). Microbiota composition and functions were confirmed by shotgun metagenomics in stool collected from a subset of individuals with paediatric onset MS (n=31) and control participants (n=61) with paired diet and stool data. Shotgun metagenomics data were analysed by (B) MetaPhlAn3 (microbiota composition) and (C) HUMAnN3 (microbiota functions). (D) Microbial metabolites identified by shotgun metagenomics to be significantly altered in MS were presented. *p<0.05, **p<0.01, ***p<0.001. AX, arabinoxylan; FC, fold change; FOS, fructooligosaccharide; HC, healthy control; MS, multiple sclerosis; ns, not significant.
Credit: By Stephanie L Tollenaar, Reihane Khorasaniha, Heather Armstrong et al.
Dietary fibre is widely regarded as beneficial due to its fermentation by gut microbiota into short-chain fatty acids (SCFAs), which exert anti-inflammatory effects. However, emerging evidence suggests that this benefit depends critically on microbial composition and function. In multiple sclerosis (MS), gut dysbiosis and reduced SCFA production have been consistently reported, raising questions about whether all fibre types are equally beneficial in this context. This study by Tollenaar, Khorasaniha et al. investigates whether impaired microbial fermentation in MS alters host responses to β-fructans, a common prebiotic fibre.
Key Findings
(1) Reduced β-fructan intake and impaired microbial fermentation in MS
Patients with paediatric-onset MS consumed significantly less β-fructans than healthy controls, despite similar total fibre intake. This reduction was accompanied by:
- Lower abundance of fibre-fermenting bacteria (e.g., Bifidobacterium)
- Reduced levels of enzymes involved in β-fructan metabolism
These findings indicate a diminished microbial capacity to process specific fibre subtypes in MS.
(2) Altered diet–microbiome interactions
In healthy individuals, higher β-fructan intake correlated with beneficial microbes such as Lactobacillus. In contrast, in MS patients, β-fructan intake was associated with potentially pro-inflammatory taxa, including Enterobacter and Desulfovibrio.
This divergence suggests that the same dietary component may have fundamentally different biological effects depending on the host microbiome.
(3) Unfermented β-fructans exacerbate neuroinflammation
Using a germ-free experimental autoimmune encephalomyelitis (EAE) mouse model (lacking fibre fermentation capacity), the authors demonstrated that β-fructan supplementation:
- Worsened neurological symptoms
- Increased spinal cord demyelination
- Enhanced immune activation in both gut and central nervous system
These findings provide mechanistic evidence that unfermented fibres can promote disease activity via the gut–brain axis.
(4) Immune mechanisms linking gut and CNS
The study identified key immune pathways involved in this process:
- Increased CXCR1⁺ macrophages and CD4⁺ T cells in the CNS
- Activation of Th1-related immune responses in the gut
- Upregulation of inflammatory signalling pathways
These results suggest that unfermented β-fructans may trigger gut immune activation, which subsequently drives CNS inflammation and demyelination.
Clinical and Research Implications
Precision nutrition in MS
This study challenges the conventional view that “more fibre is always better.” Instead, it supports a microbiome-dependent model of dietary response, where:
- Fibre benefits require intact microbial fermentation
- Specific fibres (e.g., β-fructans) may be harmful in certain patients
Potential clinical considerations
- High-dose prebiotic supplements may not be universally safe in MS
- Whole-food sources of fibre in moderate amounts may remain beneficial
- Microbiome profiling could guide personalised dietary recommendations
Future directions
The authors highlight the need for:
- Longitudinal human studies to determine causality
- Humanised microbiome models
- Clinical trials testing fibre subtype–specific interventions
Conclusion
This study provides compelling evidence that impaired gut microbial function in MS can transform beneficial dietary fibres into pro-inflammatory agents. By linking microbiome dysfunction, diet, and neuroinflammation, the findings underscore the importance of personalised nutrition strategies and caution against indiscriminate fibre supplementation in autoimmune diseases.
See the article:
Tollenaar SL, Khorasaniha R, Jovel J, et al. 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;4:e100296. doi:10.1136/egastro-2025-100296
About eGastroenterology
eGastroenterology, a BMJ journal partnered with Gut and launched by leading scientists in gastroenterology and hepatology, has been indexed in the Web of Science Core Collection (ESCI), PubMed, DOAJ, Scopus, CAS, ROAD, and many other major international databases within just two years of its launch. The journal is expecting to receive its first Impact Factor in June 2026.
For more information, please visit: egastroenterology.bmj.com and follow us on Twitter (@eGastro_BMJ).
Sign-up to Email Alerts for eGastroenterology: https://emails.bmj.com/k/Bmj/jausu/egastroenterology