**Background:** Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease affecting approximately 2.3 million people worldwide, with increasing incidence (50–300 per 100,000). While its etiology remains unclear, interactions between genetic and environmental factors—including gut microbiota (GM) alterations—are implicated. The gut-brain axis, mediated partly by microbial metabolites like short-chain fatty acids (SCFAs), may influence CNS inflammation. SCFAs, particularly butyric acid, have immunomodulatory functions via T regulatory cell enhancement and Th17 suppression. This systematic review aimed to investigate the relationship between intestinal microbiota and MS.
**Methods:** A systematic review was conducted in the first trimester of 2022, following PRISMA guidelines. Six electronic databases (PubMed, Cochrane Library, ProQuest, CINAHL, ScienceDirect, Scopus) were searched for studies published between January 2018 and March 2022. The PICO question was: "Does a relation exist between intestinal microbiota and MS?" Inclusion criteria were: analytic observational studies (cohort, cross-sectional, case-control) in MS patients aged 18–70; articles analyzing GM or SCFAs in intestinal metabolome; studies in English or Spanish. Exclusion criteria included reviews, meta-analyses, interventional studies, studies without control groups, and those analyzing metabolome without SCFAs. Study selection was performed independently by two authors, with a third resolving disagreements. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS), with scores ≥7 considered high quality.
**Key Results:** From 1,004 initial records, 12 studies met inclusion criteria, comprising 570 MS cases and 478 controls (54% MS). Among MS cases, 53% (301/570) had relapsing-remitting MS (RRMS), 9.3% (53/570) primary progressive MS (PPMS), and 3.5% (20/570) benign MS (BMS); 34.4% (196/570) were unspecified subtype. The female-to-male ratio was 68%/32% in MS and 61.5%/38.5% in controls. Studies originated from the USA (3), Spain (2), Italy (1), Belgium (1), China (1), Brazil (1), Israel (1), Egypt (1), and Russia (1). All 12 studies scored low risk of bias on NOS.
REGARDING ALPHA DIVERSITY
one study found decreased diversity in RRMS, one found increased diversity in PPMS, and eight found no significant differences. At the phylum level, Firmicutes decreased in 40% of studies and increased in 20%; Bacteroidetes increased in 30% and decreased in 10%. At the genus level, consistent decreases were observed in Bifidobacterium (2 studies), Roseburia (2 studies), Coprococcus (2 studies), Butyricicoccus (2 studies), Lachnospira (2 studies), Dorea (2 studies), Faecalibacterium (2 studies), and Prevotella (2 studies). Consistent increases were found in Akkermansia (3 studies), Blautia (3 studies), and Ruminococcus (2 studies).
FOUR STUDIES ANALYZED SCFA LEVELS
serum butyrate was decreased in MS patients (2 studies), serum acetate was increased (1 study), and fecal SCFAs showed a decreasing trend in MS (1 study). No significant differences in propionate were found.
**Clinical Implications:** This review demonstrates consistent gut microbiota dysbiosis in MS patients, characterized by depletion of SCFA-producing bacteria (particularly butyrate producers) and enrichment of mucin-degrading taxa like Akkermansia. The reduction in butyrate—a key immunomodulatory metabolite—may contribute to the chronic inflammatory state underlying MS. These findings suggest that GM characterization could serve as a diagnostic biomarker, and that GM modulation (e.g., via probiotics, dietary fiber, or disease-modifying therapies) represents a potential therapeutic strategy. However, the authors note that a cause-effect relationship remains unestablished, and significant methodological heterogeneity across studies (differences in stool collection, 16S rRNA region targeted, MS subtypes, medications, diet, and geography) limits firm conclusions. Future research should standardize methodologies and investigate whether dysbiosis is a cause or consequence of MS.