Over the past decade, growing evidence has highlighted the significant role of the gut microbiota in the pathogenesis and progression of multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system. Although overall microbial diversity in individuals with MS may resemble that of healthy controls, consistent alterations in the relative abundance of specific bacterial taxa and their metabolic outputs have been documented. These microbial shifts are closely associated with immune dysregulation and disease activity, and may be modulated by factors such as pharmacological treatment, dietary patterns, and genetic predisposition. As a result, the gut microbiota is increasingly recognized not only as a potential biomarker for MS diagnosis and prognosis but also as a promising target for therapeutic intervention.
Gut microbiota in MS
Multiple sclerosis is linked to notable shifts in gut microbiota composition, particularly among bacterial taxa involved in immune regulation. This imbalance is marked by a reduction in beneficial anti-inflammatory microbes and an increase in species that may promote inflammation, suggesting a potential role of the gut microbiome in MS pathogenesis.
Beneficial microbes such as Faecalibacterium, Prevotella, Roseburia, Bifidobacterium, and members of Clostridia clusters XIVa and IV—known for their roles in maintaining immune tolerance and producing short-chain fatty acids (SCFAs) —are consistently found at reduced levels. In contrast, taxa including Akkermansia*, Methanobrevibacter, Blautia, Ruminococcus, and Actinomyces are frequently elevated in MS patients. This shift suggests a microbial environment that may favor immune activation and inflammation, potentially contributing to disease onset and progression (Chen et al., 2016; Jangi et al., 2016; Lin et al., 2024; Mirza et al., 2020; Miyake et al., 2015; Ordoñez-Rodriguez et al., 2023).
* You might think Akkermansia is one of the good guys—after all, it’s famous for keeping your gut lining in shape. But don’t be fooled by its clean-cut reputation! When microbial diversity drops and mucin becomes its all-you-can-eat buffet, Akkermansia can go rogue. Instead of protecting the gut, it may start poking holes in the barrier, stirring up inflammation, and giving your immune system a reason to panic. So yes, it’s helpful… until it’s not.
These compositional shifts are not merely correlative—they appear to reflect underlying disease dynamics. In untreated, active MS, increased bacterial richness and the presence of specific taxa have been linked to higher relapse rates and elevated inflammatory markers such as IL-17A and IL-6 (Thirion et al., 2023). Conversely, individuals with non-active MS tend to exhibit higher levels of Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, both known producers of anti-inflammatory metabolites like butyrate. Supporting a causal role, experimental studies have demonstrated that microbiota from MS patients can induce central nervous system autoimmunity when transferred to germ-free animal models (Berer et al., 2017; Correale et al., 2022).
Modulating factors
Several external and host-related factors influence gut microbiota composition in MS. Immunomodulatory therapies such as glatiramer acetate and vitamin D supplementation have been shown to promote the growth of beneficial bacterial taxa (Cantarel et al., 2015; Mirza et al., 2020). Additionally, dietary habits, obesity, and host genetic background interact with the microbiota, shaping both disease susceptibility and progression (Montgomery et al., 2024; Samara et al., 2023; Schumacher et al., 2024).
Microbial metabolites and therapeutic potential
Many of the bacterial taxa altered in MS are involved in the production of SCFAs, particularly butyrate, which plays a key role in regulating inflammation and maintaining gut barrier integrity. A reduction in SCFA-producing bacteria may contribute to chronic immune activation and inflammation in MS (Ordoñez-Rodriguez et al., 2023; Schumacher et al., 2024). Consequently, strategies aimed at modulating the gut microbiota—through dietary interventions, probiotics, or targeted microbial therapies—are emerging as promising avenues for future MS treatment (Altieri et al., 2023; Correale et al., 2022; Turner et al., 2024).
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