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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Limited Gut Microbiome Differences Between Relapsing–Remitting and Secondary Progressive Multiple Sclerosis: A Shotgun Metagenomic Study

  • Cristiana Vacaras1,2
  • Vitalie Vacaras1,2
  • Cristina Nistor1,2
  • Stefan Cristian Vesa3
  • Cristina Jucan1,2
  • Ioana Monica Furdui1,2
  • Stefan Strilciuc4
  • Emanuel Stefanescu5
  • Diana Chira2
  • Alexandru Rafila6
  • Dafin F. Muresanu1,2
6 affiliations
  1. 1Neurology Department, Cluj Emergency County Hospital, 400012 Cluj-Napoca, Romania
  2. 2Department of Neurosciences, Faculty of Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
  3. 3Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania
  4. 4Department of Genomics, MEDFUTURE Institute for Biomedical Research, Iuliu Hațieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
  5. 5RoNeuro Institute for Neurological Research and Diagnostic, 400364 Cluj-Napoca, Romania
  6. 6Department of Microbiology, Carol Davila University of Medicine and Pharmacy, Dionisie Lupu Street, 050474 Bucharest, Romania
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Abstract

The gut microbiome may contribute to multiple sclerosis (MS) pathophysiology, but its relationship with disease phenotype and progression remains unclear. To characterize taxonomic and functional gut microbiome differences between relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) and their associations with neurological disability and circulating biomarkers. This cross-sectional study included 89 participants (30 healthy controls, 29 RRMS, and 30 SPMS). Shotgun metagenomic sequencing was used to assess microbial diversity, taxonomic profiles, and predefined short-chain fatty acid (SCFA)-related pathways, integrated with disability measures and serum GFAP, NfL, and S100B. SPMS participants were substantially older than those with RRMS (median 49.0 vs. 31.0 years), prompting age-adjusted analyses and an age-overlap sensitivity analysis. Alpha diversity and overall microbial community composition were similar across groups. SPMS showed greater interindividual microbial community dispersion than RRMS in the full cohort, with a similar direction and magnitude but attenuated statistical significance in the age-overlap sensitivity analysis. Exploratory taxonomic signals were not confirmed by FDR-controlled analyses. No robust phenotype-specific differences in predicted SCFA-related pathways or associations of taxonomic or functional features with disability or circulating biomarkers were identified. Greater microbial community dispersion in SPMS was observed in the full cohort, but this finding was attenuated in the age-overlap sensitivity analysis and should be considered preliminary. Overall, these findings do not support a distinct SPMS-associated gut microbiome signature, although potential phenotype-related differences cannot be excluded.

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Cite

BibTeXRIS
BibTeX
@article{vacaras2026limited,
  title = {{Limited Gut Microbiome Differences Between Relapsing–Remitting and Secondary Progressive Multiple Sclerosis: A Shotgun Metagenomic Study}},
  author = {Cristiana Vacaras and Vitalie Vacaras and Cristina Nistor and Stefan Cristian Vesa and Cristina Jucan and Ioana Monica Furdui and Stefan Strilciuc and Emanuel Stefanescu and Diana Chira and Alexandru Rafila and Dafin F. Muresanu},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209166},
  url = {https://www.mdpi.com/1422-0067/27/20/9166},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Limited Gut Microbiome Differences Between Relapsing–Remitting and Secondary Progressive Multiple Sclerosis: A Shotgun Metagenomic Study
AU  - Cristiana Vacaras
AU  - Vitalie Vacaras
AU  - Cristina Nistor
AU  - Stefan Cristian Vesa
AU  - Cristina Jucan
AU  - Ioana Monica Furdui
AU  - Stefan Strilciuc
AU  - Emanuel Stefanescu
AU  - Diana Chira
AU  - Alexandru Rafila
AU  - Dafin F. Muresanu
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209166
UR  - https://www.mdpi.com/1422-0067/27/20/9166
AB  - The gut microbiome may contribute to multiple sclerosis (MS) pathophysiology, but its relationship with disease phenotype and progression remains unclear. To characterize taxonomic and functional gut microbiome differences between relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) and their associations with neurological disability and circulating biomarkers. This cross-sectional study included 89 participants (30 healthy controls, 29 RRMS, and 30 SPMS). Shotgun metagenomic sequencing was used to assess microbial diversity, taxonomic profiles, and predefined short-chain fatty acid (SCFA)-related pathways, integrated with disability measures and serum GFAP, NfL, and S100B. SPMS participants were substantially older than those with RRMS (median 49.0 vs. 31.0 years), prompting age-adjusted analyses and an age-overlap sensitivity analysis. Alpha diversity and overall microbial community composition were similar across groups. SPMS showed greater interindividual microbial community dispersion than RRMS in the full cohort, with a similar direction and magnitude but attenuated statistical significance in the age-overlap sensitivity analysis. Exploratory taxonomic signals were not confirmed by FDR-controlled analyses. No robust phenotype-specific differences in predicted SCFA-related pathways or associations of taxonomic or functional features with disability or circulating biomarkers were identified. Greater microbial community dispersion in SPMS was observed in the full cohort, but this finding was attenuated in the age-overlap sensitivity analysis and should be considered preliminary. Overall, these findings do not support a distinct SPMS-associated gut microbiome signature, although potential phenotype-related differences cannot be excluded.
SN  - 1422-0067
ER  -