Epilepsy affects an estimated 70 million people across the world, making it the third most common type of neurological disorder.

The condition affects neuronal activity in the brain, producing behavioral changes and triggering sudden seizures. While antiepileptic drugs have helped reduce the burden of disease significantly, reports suggest that at least 40% of epileptic patients continue to suffer from seizures.

Additionally, patients who respond to treatment also report a high prevalence of debilitating side effects. Researchers have therefore been looking for safer and more effective options in the treatment of epilepsy.

This has prompted a closer look at the pathophysiology of epileptic seizures, highlighting the associated with inflammation and gut health.

Continue reading to learn exactly how gut inflammation affects the brain…

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How Gut Inflammation Affects Epilepsy

Although there’s a lot that we still don’t understand about the gut-brain connection, researchers have been studying the link closely. Their findings have lent support to the idea that neurological and neuropsychological problems like schizophrenia, bipolar disorder, and epileptic seizures might be connected to imbalances in the microbiome.

The microbiome refers to the diverse microbial flora that resides in the gastrointestinal tract, influencing various aspects of health. Studies suggest that disruptions to this healthy balance of gut bacteria can trigger immune overreaction and inflammation of the GI tract. These effects aren’t restricted to the gut, but can also affect the brain.

German researchers at the University of Marburg, found that gut inflammation can induce synthesis of cytokines by neurons; they can then migrate to the brain, changing the permeability of the blood-brain barrier.

Cytokines are increasingly regarded as a connecting factor between inflammatory bowel disorders and epilepsy. It’s worth noting that gut microbiota influences the release of cytokines and neuroendocrine transmitters from immune cells and endocrine cells in the mucosal lining.

Research shows that cytokines can increase severity and susceptibility to seizures in animal models. These findings have also supported by subsequent studies, including one that was published in the journal Medicine.

The authors stated that “the association between SLE (systemic lupus erythematosus) and the development of IBS or epilepsy, was consistent with the literature to support that inflammatory cytokines or cells may play a crucial role in the pathogenesis of IBS and epilepsy”.

They note that there is increased synthesis and release of cytokines (pro-inflammatory) and chemokines in autoimmune disorders. Some studies also demonstrate physical changes in the brain in patients suffering from inflammatory gut diseases like IBS.

It is speculated that the GI tract mucosal membrane may be adversely affected or altered as a result of early life infections, as well as dietary choices, antibiotic usage, chemotherapy, and radiation treatment.

Epilepsy: How Gut Inflammation Affects The Brain

How Diet Can Reduce Gut Inflammation & Seizures

The low-carb, high-fat ketogenic diet may have gained popularity in recent years for possible weight loss benefits, but its primary purpose has been to treat refractory epilepsy.

This condition affects more than one-third of epileptic patients and is hard to control, with anticonvulsive drugs being ineffective. The diet forces your body to turn to body fat or ketones for energy, instead of relying on glucose.

The rise in ketone bodies within the blood is described as ketosis, which is associated with a reduction in seizures. A more recent study also showed promising results, halving the frequency of seizures and providing benefits even after discontinuation of the diet. However, there’s more to the diet than ketosis.

Scientists have begun to identify what may be an important mechanism of action in the keto diet – its influence on gut microbiota. They believe that this influence modulates metabolic, neurological, and metabolic pathways, thereby enhancing protection against seizures.

A paper published in the journal Cell, identified two specific bacteria as crucial in seizure protection. Both strains flourish with the keto diet. The diet was found to be ineffective when antibiotics were administered, as they destroyed these strains of bacteria. It is believed that the presence of these bacteria in the gut raises levels of the inhibitory neurotransmitter GABA.

There are other dietary modifications that can help improve gut microbial biodiversity. Although more research is needed, existing studies do support recommendations of pre and probiotics.

Adding such ingredients to a balanced diet can help to restore microbiome balance, reducing gut inflammation. Probiotics include foods like plain yogurt, cottage cheese, fresh sauerkraut, kefir, apple cider vinegar, and miso. Prebiotics, on the other hand, include foods that contain specific types of fiber that help probiotic bacteria to flourish. Oats, bananas, berries, leeks, legumes, and beans are some foods that contain prebiotic fiber. The efficacy of pre and probiotic supplementation can vary, however, depending on the type of inflammatory bowel disease.

In addition to preserving a healthy balance of gut microbes, certain phytonutrients and antioxidants may also protect against epileptic seizures. Resveratrol, a plant polyphenol, may offer neuroprotective benefits that limit the effects of neurodegenerative disorders and seizures because of antioxidant and anti-inflammatory properties.

Similarly, curcumin, a phytopolylphenol from turmeric, could help reduce inflammation that is associated with chronic seizures. Low Glycemic Index diets may also have a role to play in seizure management, especially in children. Some reports have shown that the diet can reduce the frequency of seizures, without the risk of adverse effects and the restrictiveness of the keto diet.

A New Approach For Epilepsy Treatment

In light of the growing evidence that points to mutual facilitation of inflammation and epilepsy, researchers are looking for new strategies to block undesired inflammatory signaling. Blocking such excessive inflammatory processes in the brain could help reduce the frequency and severity of seizures.

Researchers are looking at small molecules that target proinflammatory perpetrators with a high level of precision. Although only in preclinical stages, these studies will help in the development of precise anti-inflammatory therapies for epilepsy and seizures.

Genetic therapy may also have a lot to offer in the near future, as genes have a major role to play in rare forms of epilepsy. In most cases, we still have no understanding of the specific genes involved. Identifying the responsible genes will make it easier to provide targeted and effective therapy.

References:

Engel, Jerome. “What can we do for people with drug-resistant epilepsy? The 2016 Wartenberg Lecture” Neurology vol. 87,23 (2016): 2483-2489.

Mayer, Emeran A et al. “Gut microbes and the brain: paradigm shift in neuroscience” Journal of neuroscience: the official journal of the Society for Neuroscience vol. 34,46 (2014): 15490-6.

Li, Gang, et al. “Cytokines and Epilepsy.” Seizure, vol. 20, no. 3, 2011, pp. 249–256., doi:10.1016/j.seizure.2010.12.005.

Riazi, Kiarash, et al. “Contributions of Peripheral Inflammation to Seizure Susceptibility: Cytokines and Brain Excitability.” Epilepsy Research, vol. 89, no. 1, 2010, pp. 34–42., doi:10.1016/j.eplepsyres.2009.09.004.

Chen, Chien-Hua, et al. “Irritable Bowel Syndrome Increases the Risk of Epilepsy.” Medicine, vol. 94, no. 36, 2015, doi:10.1097/md.0000000000001497.

Piché, Mathieu, et al. “Thicker Posterior Insula Is Associated With Disease Duration in Women With Irritable Bowel Syndrome (IBS) Whereas Thicker Orbitofrontal Cortex Predicts Reduced Pain Inhibition in Both IBS Patients and Controls.” The Journal of Pain, vol. 14, no. 10, 2013, pp. 1217–1226., doi:10.1016/j.jpain.2013.05.009.

Freeman, J. M., et al. “The Ketogenic Diet: One Decade Later.” Pediatrics, vol. 119, no. 3, 2007, pp. 535–543., doi:10.1542/peds.2006-2447.

Martin-Mcgill, Kirsty J, et al. “Ketogenic Diets for Drug-Resistant Epilepsy.” Cochrane Database of Systematic Reviews, 2018, doi:10.1002/14651858.cd001903.pub4.

Olson, Christine A., et al. “The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.” Cell, vol. 173, no. 7, 2018, doi:10.1016/j.cell.2018.04.027.

Scaldaferri, Franco et al. “Gut microbial flora, prebiotics, and probiotics in IBD: their current usage and utility” BioMed research international vol. 2013 (2013): 435268.

Martinc, Boštjan et al. “Antioxidants as a preventive treatment for epileptic process: a review of the current status” Current neuropharmacology vol. 12,6 (2014): 527-50.

Shetty, Ashok K. “Promise of resveratrol for easing status epilepticus and epilepsy” Pharmacology & therapeutics vol. 131,3 (2011): 269-86.

Coppola, Giangennaro, et al. “Low Glycemic Index Diet in Children and Young Adults with Refractory Epilepsy: First Italian Experience.” Seizure, vol. 20, no. 7, 2011, pp. 526–528., doi:10.1016/j.seizure.2011.03.008

 

 

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