In this cross-sectional shotgun metagenomic study of 89 participants, alpha diversity, overall community composition, predicted SCFA-related pathways, and associations with disability and serum biomarkers did not differ robustly between RRMS and SPMS, so the findings do not support a distinct SPMS-associated gut microbiome signature, although potential phenotype-related differences cannot be excluded.
Alpha diversity and overall microbial community composition were similar across healthy controls, RRMS, and SPMS groups.
SPMS participants showed greater interindividual microbial community dispersion than RRMS participants in the full cohort.
SPMS participants were substantially older than RRMS participants, which required age-adjusted and age-overlap sensitivity analyses.
Exploratory taxonomic differences were not confirmed after false discovery rate (FDR) control.
No robust phenotype-specific differences were found in predicted short-chain fatty acid (SCFA)-related pathways.
No robust associations were identified between taxonomic or functional microbiome features and neurological disability or circulating biomarkers.
Overall, the data do not support a distinct SPMS-associated gut microbiome signature, though subtle phenotype-related differences cannot be excluded.
This study compared the gut bacteria of 89 people: healthy volunteers, people with relapsing-remitting multiple sclerosis (RRMS), and people with secondary progressive MS (SPMS), a later, more disabling form. Researchers sequenced the DNA of gut microbes and also looked at the microbes' predicted ability to make short-chain fatty acids, along with disability scores and blood markers of nerve and brain cell damage (GFAP, NfL, S100B). Overall, the three groups looked quite similar. The variety of gut microbes and the overall makeup of the communities did not differ clearly. People with SPMS showed somewhat more variation from one person to another than those with RRMS, but this was weaker when the comparison was restricted to people of similar ages. This matters because the SPMS group was much older (median 49 vs. 31 years), and age alone can affect gut bacteria. Individual bacterial differences that first appeared did not hold up after statistical correction for multiple testing, and no reliable links were found between gut microbes and disability or blood markers. This research suggests there is no clear, distinct gut microbiome signature separating SPMS from RRMS, at least in this relatively small group. The authors caution that smaller differences cannot be ruled out, and the dispersion finding is preliminary. Larger studies with better age matching would be needed to clarify this.
Vacaras C, Vacaras V, Nistor C, Vesa S, Jucan C, Furdui I, et al.. (2026). Limited Gut Microbiome Differences Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: A Shotgun Metagenomic Study.. International journal of molecular sciences. https://doi.org/10.3390/ijms27209166