Epilepsy

Children with cerebral palsy plus epilepsy (CP+E) have distinct gut microbiota compared to CP without epilepsy, suggesting epilepsy is not merely a neurological overlay but involves gut-brain axis restructuring,.

MR supports a causal link between specific gut microbiota and epilepsy risk, though the specific taxa remain under investigation.

The microbiome changes may be causally required for the anti-seizure effect: antibiotic ablation of the microbiome eliminated ketogenic diet efficacy in mice.

Epilepsy affects ~50 million people worldwide, with ~30% experiencing drug-resistant seizures. The gut-brain axis provides a mechanistic framework for understanding how intestinal dysbiosis modulates seizure thresholds through neuroactive metabolites, immune signaling, and SCFA-mediated neural communication. The strongest clinical evidence for microbiome inv

This signature draws substantially from cerebral palsy-epilepsy (CPE) comorbidity data, as most microbiome profiling in epilepsy has been conducted in this population. Mendelian randomization provides additional causal evidence for taxa-epilepsy relationships independent of CP.

Iron (depleted): Iron deficiency is common in epilepsy patients, particularly those with CP comorbidity (13-48% prevalence). Whether this represents true deficiency or hepcidin-mediated sequestration (nutritional immunity) remains unresolved. Anticonvulsant medications may compound iron malabsorption.

Arsenic (elevated): Most influential metal on infant gut microbial alpha diversity; environmental arsenic exposure during neurodevelopment may contribute to seizure susceptibility.

Anticonvulsant medications represent the dominant environmental factor shaping the epilepsy gut microbiome. GABA-ergic antiepileptic drugs are associated with increased constipation and elevated cytokine levels, creating an iatrogenic loop: medications prescribed for seizures alter gut ecology in ways that may perpetuate neuroinflammation. Environmental meta

Elevated IL-1beta, IL-6, TNF-alpha: Systemic inflammatory markers are elevated in epilepsy, particularly in the CPE population. Salivary IL-1beta correlates strongly with systemic levels (R=0.720).

Depleted butyrate: The comprehensive loss of butyrate-producing taxa (Faecalibacterium, Roseburia, Blautia, Anaerostipes) creates a profound SCFA deficit. Butyrate normally crosses the BBB and promotes myelination via HDAC inhibition.

akkermansia muciniphila is an MR-validated risk factor for epilepsy, with particularly strong association for focal epilepsy (OR=1.739). Akkermansia degrades mucin, increasing mucosal permeability and exposing the immune system to bacterial antigens. The KEGG functional analysis attributes elevated immune system disease risk to Akkermansia overgrowth.

streptococcus (4.70% in CPE) drives neurodegenerative disease risk via KEGG pathway analysis, primarily through IL-6 and TNF-alpha elevation. Strong co-occurrence with Actinomyces (r=0.833) suggests an oral-origin consortium.

Betaproteobacteria (class) and Burkholderiales (order) are MR risk factors (OR=1.357 and 1.336 respectively). Burkholderiales includes metal-tolerant species that thrive in heavy-metal contaminated environments.

The SCFA-producing community is comprehensively depleted in epilepsy: bacteroides (from dominant to 10.94%), faecalibacterium prausnitzii (0.78%), blautia (1.44%), Ruminococcus (0.01%), roseburia (0.00%), and Anaerostipes (0.04%)—all P<0.001.

bacteroides fragilis and Dialister invisus are depleted specifically in CP+epilepsy (not CP alone), and both are linked to kynurenine pathway modulation. Their loss may shift tryptophan metabolism toward excitotoxic quinolinic acid.

Eubacterium xylanophilum group is MR-validated as protective (OR=0.816).

Acetate accumulation: With Anaerostipes and Faecalibacterium depleted, their normal co-production of butyrate from acetate is lost, causing acetate to accumulate. Excess acetate activates the parasympathetic nervous system and may directly trigger seizures.

Kynurenine pathway shunting—The balance between neuroprotective kynurenic acid (KA, NMDA antagonist) and neurotoxic quinolinic acid (QUIN, NMDA agonist) shifts toward QUIN under inflammatory conditions. B. fragilis depletion exacerbates this shift.

Oral-gut translocation—Streptococcus and Prevotella enrichment in the gut reflects oral pathobiont colonization of intestinal niches, particularly relevant in CPE where 96.3% have periodontitis.

Paradoxical diversity increase—CPE gut has higher Shannon diversity (2.33 vs 1.49) than healthy controls, but this reflects pathobiont expansion into vacated commensal niches, not ecological health.

The highest overlap in the knowledge base. CP and epilepsy share iron/zinc depletion, comprehensive SCFA-producer loss, Streptococcus/Akkermansia enrichment, oral-gut translocation, and neuroinflammatory mechanisms. CP+epilepsy (CPE) has a distinct microbiome from CP without epilepsy, suggesting epilepsy adds a specific ecological perturbation.