Uncovering Roles for the Human Gut Microbiome in Protecting Against Pediatric Refractory Epilepsy
Abstract number :
3.343
Submission category :
10. Dietary Therapies (Ketogenic, Atkins, etc.)
Year :
2021
Submission ID :
1826187
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:52 AM
Authors :
Gregory Lum, BS - University of California Los Angeles; Christine Olson - University of California Los Angeles; Beck Reyes - University of California Los Angeles; Joyce Matsumoto - University of California Los Angeles; Jorge Paramo - University of California Los Angeles; Elaine Hsiao - University of California Los Angeles
Rationale: The ketogenic diet (KD) is a mainstay clinical treatment for children with refractory epilepsy; however, it is difficult to implement, maintain and manage, due to its severe restrictiveness and side effects. Exactly how the KD reduces seizure symptoms when other anti-epileptic drugs are ineffective is poorly understood. The microbiome is a key intermediary between diet and host metabolism, neural activity, and behavior. Recent studies report that the KD modifies the gut microbiome across mouse models of refractory epilepsy and that these changes in the microbiome are necessary and sufficient for mediating the anti-seizure effects of the KD in mice. Whether these pre-clinical findings are relevant to human pediatric epilepsy and the clinical KD remains unclear. This study aims to determine effects of the human gut microbiome from pediatric epilepsy patients in mediating the anti-seizure effects of the clinical KD.
Methods: Matched fecal samples from pediatric epilepsy patients were collected before starting clinical KD treatment (pre-KD) and at 1 month after initiation of KD therapy (post-KD). Matched pre-KD and post-KD samples were each transplanted into cohorts of germ-free (GF) mice, and resultant humanized mice were tested for seizure susceptibility in the 6-Hz psychomotor seizure assay.
Results: Remarkably, mice colonized with the post-KD samples exhibited increased seizure thresholds compared to those colonized with matching pre-KD samples. 16s rRNA gene sequencing and shotgun metagenomic profiling of patient donor and recipient mouse fecal material confirmed transplantation fidelity and revealed key differences in functional potential between pre-KD and post-KD microbiomes that correlate with seizure protection.
Conclusions: These preliminary findings suggest that diet-induced changes in the human gut microbiome may contribute to seizure protection in response to the clinical KD.
Funding: Please list any funding that was received in support of this abstract.: Mallinckrodt Foundation.
Dietary Therapies (Ketogenic, Atkins, etc.)