Gut Microbiota Emerges as a Novel Therapeutic Strategy for Drug-Resistant Epilepsy: Multi-Center Trials Underway

“The Gut Microbiota–Gut–Brain Axis” has been a hot research area in the past decade.Its mechanism of modulating human health and disease states through the complex interactions between the gut microbiota and the brain has been widely recognized in clinical practice.

In previous issues, Chengguo Bureau has partnered withThe Second Affiliated Hospital of Guangzhou Medical University(hereinafter referred to as the Second Affiliated Hospital of Guangzhou Medical University)Director Deng YuhongAn in-depth discussion was held on research into the “gut-brain axis.” At that time, Deng Yuhong stated, “The nutritional gut microbiota technology currently available at the Second Affiliated Hospital of Guangzhou Medical University is already able to assist in the treatment of conditions such as abnormal neurodevelopment in children, malignant tumors, autoimmune diseases, diabetes, and gout. The team is still actively developing new indications.”

A year has passed, and Deng Yuhong’s team has returned to Chengguo Bureau with new scientific research achievements. On the “18th International Epilepsy Care Day,” she shared with usTreating Epilepsy Through the Gut Microbiotanew strategies.

Epilepsy is a paroxysmal neurological disorder, widely recognized in clinical practice as being caused by recurrent abnormal electrical discharges in the brain. Although epilepsy does not directly pose a life-threatening risk to patients, its unpredictable seizures place them in constant danger.

To treat epilepsy, clinically available therapies have been developedMedications, Surgery, Vagus Nerve Stimulation, Ketogenic Dietmethods.

Pharmacotherapy is currently one of the most commonly used approaches. Approximately 60% of patients with epilepsy can achieve seizure control through medication, and its widespread adoption is further facilitated by advantages such as low cost due to inclusion in national medical insurance coverage. In recent years, studies have found thatEpilepsy medications still fail to address long-term patient outcomes, merely delaying disease progression.

Over 30% of patients still progress to drug-resistant epilepsy despite 2–3 years of standardized pharmacological treatment. Most patients may require long-term or even lifelong medication, and prolonged drug use can lead to adverse effects such as hepatic impairment, bone marrow suppression, and cognitive decline.

Surgical treatment is primarily performed by resecting the epileptogenic focus. However, the characteristics of the focus vary among different types of epilepsy.Some lesions are diffuse, and seizures may still occur after resection.. Meanwhile, the assessment of localized lesions demands a high level of expertise from physicians and carries a higher risk coefficient.

Vagus nerve stimulation is a novel therapy that has recently emerged alongside advances in brain science. It primarily treats epilepsy by implanting a vagus nerve stimulator subcutaneously. According to publicly available clinical data, this approach achieves an efficacy rate of 50–60% in refractory epilepsy, butFew products have been approved; moreover, their high cost and the need for invasive implantation hinder widespread adoption.

Deng Yuhong’s team has conducted extensive research on the treatment of neurological disorders through nutritional gut microbiota modulation. Additionally, Dr. Deng received specialized training in epilepsy at Austin Health, affiliated with the University of Melbourne in Australia. Consequently, the team has maintained a strong focus on epilepsy treatment.

At an international nutrition conference in 2018, the team discovered that overseas researchers were also attempting to treat epilepsy through gut microbiota modulation, which convinced the team of the significant potential in this direction.

Following the conference, the team actively conducted research. In 2021, the team discovered that Bacteroides fragilis could serve as an adjunctive therapy for refractory epilepsy. Trial data indicated that after four months of treatment with a Bacteroides fragilis-based adjunctive medication, the efficacy rate in epilepsy management was 61.1% (defined as a ≥50% reduction in seizure frequency). This study was“A Preliminary Clinical Study on the Efficacy of Bacteroides fragilis BF839 as an Adjunctive Therapy for Refractory Epilepsy”Published under the name , this also marks the world’s first report on a study suggesting that a single gut bacterial strain (Bacteroides fragilis BF839) may be effective in treating epilepsy.

Paper Screenshot

In the following years, the team continued to conduct in-depth research. In 2022, they completed a study using probiotics (Bf839) alone,A Retrospective Study of 15 Newly Diagnosed Patients with a Considered Diagnosis of “Probable Autoimmune-Associated Epilepsy”In 2023, published“Probiotics can effectively treat refractory epilepsy and autoimmune-related epilepsy, improve comorbidities in patients, and no serious or long-term side effects have been found in epilepsy patients taking probiotics.”perspectives have advanced the development of gut microbiota-based therapies for epilepsy.

As an innovative treatment regimen, efficacy is paramount. Deng Yuhong stated, “Existing data have demonstrated that this therapy is highly suitable for use as a diagnostic therapeutic tool.”

For refractory epilepsy, the short-term efficacy rate of this therapy (with efficacy defined as a >50% reduction in seizure frequency) has reached 30–60%, whereas the short-term efficacy rates of currently marketed antiepileptic drugs range from 40% to 50%.From this perspective, the therapeutic effects are virtually indistinguishable.

In terms of recurrence rate, this therapy achieved a one-year seizure-free rate of 73% in patients with an initial diagnosis of “probable immune-related epilepsy,” whereas valproic acid (VPA), currently the most effective antiepileptic drug, yields a one-year seizure-free rate of only 50% in patients with newly diagnosed epilepsy of various etiologies.

Deng Yuhong explained, “This is related to the different pathways of the two therapies.”

First, nutritional gut microbiota technology exerts its effects by modulating the neuro-immune-endocrine system. By regulating immune balance in patients, it alleviates cerebral inflammation, thereby improving and potentially curing epilepsy.

This is primarily achieved through the interaction of drug molecules with immune cells. Although early immunotherapy was associated with favorable prognoses, prolonged immune-mediated inflammatory responses canCausing organic damage to the patient's brain, progressing to refractory epilepsy and leading to reduced treatment efficacy.

From a safety perspective, nutritional gut microbiota technology also has a slight edge.The team utilizes *Bacteroides fragilis* strain BF839, a strain discovered and cultured in September 1983 by Professor Zhang Jiejie from the Department of Microbiology at Dalian Medical University in China. It received approval for marketing as a novel food ingredient in 1997. Years of clinical validation have demonstrated that it rarely causes adverse effects in patients. Only a very small minority of patients may experience issues such as diarrhea during the initial phase of use due to changes in gut microbiota; however, these symptoms resolve spontaneously after adaptation.

And this unique microbial community also constitutes the technological moat of China's microbiome industry:“Due to the high difficulty in cultivation, this microbial strain remains the only commercially available Bacteroides fragilis BF strain globally.”

As of press time, the project team has published three relevant clinical research papers, including single-arm, prospective, and retrospective studies conducted by the team itself, as well as a randomized, double-blind clinical study led by Dr. Cao Dezhi, Director of the Department of Neurology at Shenzhen Children’s Hospital.

Deng Yuhong revealed:“Currently, the team is co-leading a multicenter study with the Department of Neurology at West China Hospital of Sichuan University, and patient recruitment is expected to be completed this year.”

Clinically, this therapy has also gained widespread recognition. Professor Li Shichuo, the inaugural chairman of the Chinese Association Against Epilepsy, has co-authored a review article with his team to promote the adoption of this therapy.

However, over the past two decades, no bacterial strain or microbial consortium has been approved in China for use as a pharmaceutical agent. This regulatory gap has become a major bottleneck in project development. Therefore, the team looks forward to and advocates for the future approval of gut microbiota-based therapeutics, aiming to provide novel treatment options for a broader range of diseases.