Multiple sclerosis (MS) is a chronic autoimmune disease primarily affecting the central nervous system (CNS), including the brain and spinal cord. In MS, the immune system mistakenly attacks and damages myelin, the protective sheath surrounding nerve fibers, disrupting communication pathways. The gut microbiome is the vast community of trillions of microorganisms, including bacteria, viruses, and fungi, that reside in the digestive tract. Recent discoveries have established a significant, bidirectional link between this microbial community and the pathology of MS.
Understanding Multiple Sclerosis and the Gut-Brain Axis
MS is defined by demyelination and inflammation, leading to the formation of scar tissue, or lesions, within the CNS. Symptoms are highly variable, ranging from visual disturbances, numbness, and tingling to muscle weakness, coordination problems, and profound fatigue. The disease often presents as relapsing-remitting episodes where symptoms flare up and then subside.
The Gut-Brain Axis (GBA) is the foundational concept linking the digestive tract to neurological health. This constant two-way communication system involves complex neural, endocrine, and immune signaling pathways connecting the brain to the enteric nervous system, often called the “second brain,” in the gut. The gut microbiome acts as a major modulator of the GBA, influencing brain function and systemic immune responses through its metabolic activity and signaling molecules.
Microbial Dysbiosis in MS Patients
Microbial imbalance, known as dysbiosis, is consistently observed in the gut of individuals with MS compared to healthy populations. This imbalance involves distinct shifts in bacterial abundance, indicating a loss of microbial diversity necessary for immune homeostasis. The gut flora composition shifts toward a pro-inflammatory profile, contributing to the underlying autoimmune response in MS.
Researchers have identified several bacterial taxa that are either enriched or depleted in MS patients. Inflammatory bacteria, such as Akkermansia muciniphila and Acinetobacter calcoaceticus, are often found in higher abundance. Akkermansia is a mucin-degrading bacterium whose overgrowth may compromise the gut’s protective mucus layer.
Conversely, beneficial bacteria that produce anti-inflammatory molecules are significantly reduced. This depleted group includes species from the Clostridia clusters XIVa and IV, which are known for their protective properties. Other important depleted groups often include species of Bacteroides, Parabacteroides, and Faecalibacterium, which are producers of short-chain fatty acids.
Immunological Pathways Linking Gut Bacteria to MS
The altered gut flora influences the immune system through metabolites, primarily short-chain fatty acids (SCFAs). SCFAs (butyrate, propionate, and acetate) are fermentation products of dietary fiber by gut bacteria. These molecules are powerful immune modulators that promote the development and function of regulatory T-cells (Tregs), specialized cells that suppress autoimmune inflammation.
Reduced SCFA-producing bacteria in MS patients result in lower concentrations of these protective metabolites. This impairs Treg function and allows pro-inflammatory immune responses to proceed. SCFAs also maintain the integrity of the intestinal lining, preventing the passage of harmful substances into the bloodstream. Low SCFA levels compromise this barrier.
This compromised barrier leads to increased intestinal permeability, often called a “leaky gut,” allowing bacterial components to enter the circulation. For example, lipopolysaccharide (LPS), a component of the outer membrane of certain bacteria, can enter the bloodstream and trigger systemic inflammation. This cascade ultimately affects the CNS, contributing to neuroinflammation in MS.
The gut environment also polarizes T-helper cells, which are central to the autoimmune attack. MS-associated bacteria, such as enriched Akkermansia, stimulate the differentiation of pro-inflammatory T-helper 17 (Th17) cells. Th17 cells are implicated in driving the CNS inflammation and demyelination characteristic of MS.
Emerging Microbiome-Based Treatments
The recognition of the gut-MS connection has opened new avenues for therapeutic intervention aimed at restoring microbial balance. Dietary strategies are a non-invasive way to influence microbiome composition, as high-fiber diets promote the growth of beneficial SCFA-producing bacteria. Diets rich in plant-based foods, such as the Mediterranean diet, are often recommended to support a diverse gut environment.
Targeted supplementation using probiotics and prebiotics is also being investigated as a means to normalize the gut flora. Probiotics introduce live microorganisms, with studies exploring specific strains like Lactobacillus and Prevotella that may shift the immune response toward an anti-inflammatory state. Prebiotics, which are non-digestible fibers, serve as food for these beneficial bacteria, promoting their colonization and metabolic activity.
Fecal Microbiota Transplantation (FMT) is a more intensive approach involving transferring stool from a healthy donor to rapidly re-establish a diverse microbial community. While FMT is currently used to treat other gastrointestinal conditions, its application in MS is still largely experimental. Researchers are focused on safety and identifying the specific microbial profiles needed for lasting therapeutic benefits.