Gut Bacterial Dysbiosis in Children with Intractable Epilepsy

Abstract

A few published clinical studies have evaluated the association between gut microbiota in intractable epilepsy, but with inconsistent results. We hypothesized that the factors associated with the gut bacterial composition, such as age and geography, contributed to the discrepancies. Therefore, we used a cohort that was designed to minimize the effects of possible confounding factors and compared the gut microbiota between children with intractable epilepsy and healthy controls. Eight children with intractable epilepsy aged 1 to 7 years and 32 age-matched healthy participants were included. We collected stool samples and questionnaires on their diet and bowel habits at two time points and analyzed the gut microbiota compositions. In the epilepsy group, the amount of Bacteroidetes was lower (Mann–Whitney test, false discovery rate (FDR) < 0.01) and the amount of Actinobacteria was higher (FDR < 0.01) than in the healthy group. The epilepsy subjects were 1.6- to 1.7-fold lower in microbiota richness indices (FDR < 0.01) and harbored a distinct species composition (p < 0.01) compared to the healthy controls. Species biomarkers for intractable epilepsy included the Enterococcus faecium group, Bifidobacterium longum group, and Eggerthella lenta, while the strongest functional biomarker was the ATP-binding cassette (ABC) transporter. Our study identified gut bacterial dysbiosis associated with intractable epilepsy within the cohort that was controlled for the factors that could affect the gut microbiota.

Microbiota–Gut–Brain Axis and Epilepsy: A Review on Mechanisms and Potential Therapeutics

“…Microbiota richness was lower in the epilepsy group than in the HC group (13). Actinobacteria was higher in the epilepsy group than in HCs, whereas Bacteroidetes was lower (13). They identified 17 and 18 species of bacteria strongly related to epilepsy and the HC group, respectively (13).…”

“…However, they did not perform a GM diversity analysis. Lee et al conducted a study on the GM of eight children with intractable epilepsy and 32 HCs (13). Microbiota richness was lower in the epilepsy group than in the HC group (13).…”

“…Actinobacteria was higher in the epilepsy group than in HCs, whereas Bacteroidetes was lower (13). They identified 17 and 18 species of bacteria strongly related to epilepsy and the HC group, respectively (13). Enterococcus faecium, Bifidobacterium longum, and Eggerthella lenta were the strongest potential biomarkers in the intractable epilepsy group (13).…”

“…Recent advances in sequencing technology have allowed studies on the composition and function of microbiota in neurology. In recent years, some studies have suggested statistical differences in fecal microbial composition between epileptic patients and healthy people, as well as between epileptic patients before and after KD treatment, and in animal models (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). The intestinal microbiota may shape brain function through a variety of pathways and systems, including the central nervous system (CNS), the hypothalamic-pituitaryadrenal (HPA) axis, immune and inflammatory systems, and neuromodulators, and could therefore also be involved in epilepsy (Figure 1).…”

Evidences for a Role of Gut Microbiota in Pathogenesis and Management of Epilepsy

“…Some studies suggest that in refractory epilepsy there is an increase in Firmicutes and a decrease in Bacteroides relative to controls. These alterations have been reported either in adult or infants with refractory epilepsy [ 38 , 39 , 51 , 52 ]. Lactobacillus population is also suspected to have a beneficial role in epilepsy.…”