Gut–brain axis in neurology: microbiome as a modifiable risk factor for multiple sclerosis

Dear Editor, Our understanding of the gut–brain axis has grown over the past few years, as it is now known to have a quantifiable impact on the risk and progression of multiple sclerosis (MS) and that the gut microbiota may be able to be altered to influence the biology of the illness[1,2]. As clinicians, we believe that recognizing the microbiome as a practical and modifiable target is essential for future MS care. The International Multiple Sclerosis Microbiome Study and multiple meta-analyses have demonstrated changes in gut taxa in MS patients, including enrichment of Akkermansia and depletion of short-chain fatty acid (SCFA) producers such as Faecalibacterium, correlated with treatment and clinicaNot needed for LTEl outcomes[2,3]. The mechanisms by which gut communities influence Central Nervous system (CNS) autoimmunity are plausible. Microbial metabolites derived from dietary substrates, particularly SCFAs and tryptophan metabolites, influence immune programming, regulatory T-cell induction, blood–brain barrier integrity, and CNS resident cell function[1,4]. Human observational studies connect microbial profiles with relapse risk and treatment response, whereas animal models confirm that fecal transplants from MS patients can exacerbate experimental autoimmune encephalomyelitis[2,5]. Importantly, Mendelian randomization and multi-cohort analyses support a causal interpretation: genetic instruments link specific bacterial taxa, including Ruminococcus torques, to altered MS susceptibility, implying microbiome composition may contribute to disease risk[5]. To maintain clarity, only key reproducible dysbiosis patterns reduced Faecalibacterium, altered Prevotella/Bacteroides relationships, and increased oral-origin taxa are highlighted here[3]. The microbiome remains appealing for translation because it can be altered by relatively low-risk methods such as diet, probiotics, prebiotics, defined microbial consortia, and fecal microbiota transplantation. Small clinical studies and mechanistic reviews demonstrate possible benefits of SCFA-promoting dietary interventions in restoring immune balance[6,7]. Nevertheless, inter-individual variability, host genetics, technical inconsistencies, and medication effects continue to limit predictable clinical responses[1–3]. Therefore, practical next steps include integrating multi-omics datasets to identify responder phenotypes, conducting rigorously designed interventional trials, and accounting for dietary and medication confounders when testing microbiome-directed therapies[2,3]. From an author’s perspective, prioritizing microbiome-focused preventive strategies particularly in high-risk or early-stage individuals may become an important adjunct to current disease-modifying approaches. This article aligns with the TITAN Guidelines on transparency in AI use in health care[8]. In conclusion, the gut microbiota represents a meaningful and modifiable factor in MS, supported by converging clinical, molecular, and causal-inference evidence. Opportunities for prevention and adjunct therapy arise from its influence on neuroinflammation, immune modulation, and barrier integrity. The microbiome is a practical therapeutic target given its responsiveness to diet and probiotics. We strongly argue that future research should prioritize identifying causal pathways and predictive microbial markers to support personalized, microbiome-integrated MS management.