Functional microbiome shifts are associated with neuroinflammatory outcomes under dietary interventions in multiple sclerosis
Abstract
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. While disease-modifying therapies can reduce relapse rates, their limitations have spurred interest in adjunctive approaches such as fasting and ketogenic diets (FD, KD). In a randomized controlled trial, participants with relapsing–remitting MS followed FD, KD, or a control diet for 9 months, with multi-omic and clinical assessments. Our secondary analysis revealed that KD was associated with distinct gut microbial functional profiles, including enrichment of carbohydrate metabolism modules that co-occurred with lower T2 lesion volume. Stool propionate levels, however, did not correspond to the abundance of the annotated propionate production II module. Key contributors included Romboutsia timonensis , Roseburia intestinalis , and Bacteroides thetaiotaomicron . These microbial changes coincided with diet-associated changes in circulating tryptophan and indole metabolites, suggesting a system-level co-occurrence of changes along the gut-brain axis. We present evidence that KD is associated with coordinated tryptophan-related metabolite changes and species-specific functional differences alongside T2 lesion metrics. These exploratory associations warrant validation and mechanistic investigation.
Registry ClinicalTrials.gov, TRN: NCT03508414, Registration date: 25 April 2018.
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BibTeX
@article{gutmann2026functional,
title = {{Functional microbiome shifts are associated with neuroinflammatory outcomes under dietary interventions in multiple sclerosis}},
author = {Friederike Gutmann and Lina Samira Bahr and Ulrike Brüning and Víctor Hugo Jarquín-Díaz and Lajos Markó and Martin Weygandt and Rebekka Rust and Judith Bellmann-Strobl and Friedemann Paul and Sofia Kirke Forslund-Startceva and Jennifer A. Kirwan},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73464-0},
url = {https://www.nature.com/articles/s41598-026-73464-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Functional microbiome shifts are associated with neuroinflammatory outcomes under dietary interventions in multiple sclerosis
AU - Friederike Gutmann
AU - Lina Samira Bahr
AU - Ulrike Brüning
AU - Víctor Hugo Jarquín-Díaz
AU - Lajos Markó
AU - Martin Weygandt
AU - Rebekka Rust
AU - Judith Bellmann-Strobl
AU - Friedemann Paul
AU - Sofia Kirke Forslund-Startceva
AU - Jennifer A. Kirwan
PY - 2026
DA - 2026/10/03
JO - Scientific Reports
DO - 10.1038/s41598-026-73464-0
UR - https://www.nature.com/articles/s41598-026-73464-0
AB - Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. While disease-modifying therapies can reduce relapse rates, their limitations have spurred interest in adjunctive approaches such as fasting and ketogenic diets (FD, KD). In a randomized controlled trial, participants with relapsing–remitting MS followed FD, KD, or a control diet for 9 months, with multi-omic and clinical assessments. Our secondary analysis revealed that KD was associated with distinct gut microbial functional profiles, including enrichment of carbohydrate metabolism modules that co-occurred with lower T2 lesion volume. Stool propionate levels, however, did not correspond to the abundance of the annotated propionate production II module. Key contributors included Romboutsia timonensis , Roseburia intestinalis , and Bacteroides thetaiotaomicron . These microbial changes coincided with diet-associated changes in circulating tryptophan and indole metabolites, suggesting a system-level co-occurrence of changes along the gut-brain axis. We present evidence that KD is associated with coordinated tryptophan-related metabolite changes and species-specific functional differences alongside T2 lesion metrics. These exploratory associations warrant validation and mechanistic investigation. Registry ClinicalTrials.gov, TRN: NCT03508414, Registration date: 25 April 2018.
SN - 2045-2322
ER -