Understanding Gut Health and Microbiome in Epilepsy
The human gut and brain are wisely connected through the gut-brain axis—a two-way communication network involving the nervous system, immune system, and gut microbiota -microorganisms residing in the digestive system. This connection has growing relevance for neurological conditions like epilepsy, especially drug-resistant epilepsy (DRE), where anti-seizure medications do not stop seizures completely.
Emerging studies show that restoring gut microbiome balance with pre, probiotics and postbiotics (products of microbial fermentation) can positively affect seizure activity, inflammation, and neurotransmitter levels—especially GABA, a key inhibitory chemical in the brain. This research is very promising.
Microbiome and Epilepsy: Research Insights
Clinical human trials involving DRE (drug resistant epilepsy) adult patients used a comprehensive probiotic blend with the following strains:
Gómez‑Eguílaz et al. (2018) – Piloted in adults with drug-resistant epilepsy:
- Lactobacillus acidophilus
- Lactobacillus plantarum
- Lactobacillus casei
- Lactobacillus helveticus
- Lactobacillus brevis
- Bifidobacterium lactis
- Streptococcus salivarius subsp. thermophilus
Key Outcomes:
- ~29% of adult participants experienced ≥50% seizure reduction
- 77% sustained reduction at 4-month follow-up
- Increased in systemic GABA levels
- Decreased inflammatory markers such as IL-6 cytokines
Other Human Clinical Trials:
El‑Sharkawy et al. (2024) – Prospective pilot in paediatric (children) DRE:
Intervention: Daily Bacillus clausii beneficial bacteria spores for 4 months.
Results:
- 42.9% reached ≥ 50% reduction in seizure frequency.
- Significant decreases in seizure duration, frequency, severity, and inflammation (serum sCD14).
- Quality of life improved significantly; EEG changes were not statistically significant.
A randomised controlled trial in 2023 of 89 paediatric DRE patients found that adding probiotics to standard anti-seizure treatment resulted in 78.6% of those with generalised seizures achieving ≥ 50% reduction—no significant change in IL‑6, mild diarrhoea reported.
Neonatal research:
- Observational data suggests probiotic use in newborn babies with rotavirus may decrease seizure risk.
Animal studies (Pentylenetetrazol-induced seizures):
Probiotics (L. plantarum, L reuteri, L. rhamnosus and B infantis) reduced seizure severity, seizure activity and improved cognition and memory in rodent models. The mechanisms identified involved increasing brain GABA levels, and decreasing brain oxidative stress.
| Strains Used | Model | Results |
| L. rhamnosus, L. reuteri, B. infantis | PTZ-kindled rats | ↓ seizure severity, ↑ GABA, ↓ inflammation |
| B. breve | PTZ-kindled mice | ↓ tonic–clonic seizures via ILK |
| L. helveticus R0052 | Mice | ↑ seizure threshold, enhanced valproate |
| Probiotic blend with multi strains | Rats with penicillin-induced seizures | ↑ latency, ↓ IL-6, TNF-α, NO |
| Bacillus clausii | Children with DRE | 43% showed ≥50% seizure reduction |
Gut Microbiome Dysbiosis in Epilepsy
Studies also show people with epilepsy often have altered gut microbiomes. The reasons for this are not always clear, some research pointing an arrow at anti-seizure medications altering the microbiome balance. There are many causes for microbial disbalance, the most obvious being excessive course of antibiotics for infections co-occurring with epilepsy. Other potential contributing factors are: inadequate diversity of dietary fibre and plant foods, limited amounts of fermented foods, restrictive dietary practices, stress, lack of exercise and animal/nature exposure. Child birth options have a huge impact on baby’s microbiome in the first couple of years and it is vital to optimise baby’s microbiome at birth. Probiotics as well as prebiotic fibres that feed beneficial microorganisms can support microbiome balance and improve the following processes:
- GABA/glutamate neurotransmitter ratios (calming and excitatory brain chemicals produced by neurons)
- Immune regulation in the gut
- Gut lining function
- Blood Brain Barrier integrity
Particularly promising strains include (as shown in the preliminary research):
- Lactobacillus johnsonii
- Lactobacillus acidophilus
- Lactobacillus plantarum
- Lactobacillus paracasei
- Lactobacillus delbrueckii subsp. bulgaricus
- Streptococcus thermophilus
- Bifidobacterium breve, B. longum, B. infantis
- Saccharomyces boulardii, Bacillus subtilis, and kefir-derived probiotics
However, any microbiome therapy should be personalised to each individual to balance their own signature microbiome and gut health and microbiome testing is an essential tool to measure the diversity and abundance of gut microorganisms.
Ketogenic Diet & Microbiome
The ketogenic diet (KD) is widely used to treat complex epilepsies and genetic epilepsy conditions, but recent studies suggest its microbiome-shaping effects may be key to some of its success.
In mice, a probiotic combination of Akkermansia muciniphila and Parabacteroides merdae replicated the anti-seizure effects of the KD:
- Increased seizure threshold
- Improved GABA/glutamate balance
Optimising Microbiome: Choosing Probiotics for Epilepsy: What to Look For
Before considering a specific probiotic combination, it is important to ensure the dietary richness of plant fibres and fermented foods that naturally supply a host of beneficial microorganisms (bacteria, yeasts and products of microbial fermentation). By being creative with fermented foods you can ensure a continuous supply of billions of beneficial microbes together with soluble prebiotic fibres essential for microbial growth. Fermented foods can be easily incorporated into smoothies, chia puddings, soups, sandwiches, drinks, salads and pancakes!
However, where it is deemed essential to provide additional or specific probiotic strains or if fermented foods cause food sensitivities/allergies/enhanced histamine response, choosing bacterial strains needs to be personalised.
The following strains have been successfully used in preliminary clinical studies, but not everyone will benefit from them all:
Probiotic Choices
Look for multi-strain probiotic supplements that include clinically supported strains such as:
- L. acidophilus
- L. plantarum
- L. helveticus
- B. infantis
- Streptococcus thermophilus
- S. boulardii and Bacillus subtilis
- Akkermansia muciniphila
- Probiotics that do not excessively produce histamine
Gut microbiota feed on soluble fibre in the gut and produce multiple substances, one of the most studied are: Short Chain Fatty Acids SCFA (butyrate, acetate and propionate), which have been shown to modulate the brain’s excitation/inhibition balance via:
- Adjusting neurotransmitter levels (↑ GABA/5‑HT/NE (serotonin/norepinephrine ↓ glutamate) and affecting neurotransmitter signalling
- Influencing neuronal intracellular signalling (e.g., K⁺)
These microbiota-driven pathways may collectively support the state of reduced hyper-excitability, offering insight into potential novel therapeutic strategies for epilepsy through microbiome and metabolite modulation.
Conclusion
The connection between gut health, microbiome and epilepsy offers a promising area of supportive integrative care, especially for people with drug-resistant epilepsy where anti-seizure medications do not stop seizures. Human clinical and preclinical research shows that microbiome modification with pre and probiotics may reduce seizure severity, modulate inflammation, and balance neurotransmitters through the gut-brain axis. As research progresses, microbiome-based interventions may become an integrative part of holistic epilepsy management. But for now, we can optimise microbiome in epilepsy via dietary practices rich in fermented foods and soluble and insoluble fibre from plants and supplementing with specific probiotic strains and prebiotic fibres unique to each person based on their microbiome signature, diet and lifestyle.