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.

Infantile periods may have stronger genetic influences. Recently, studies on genetic defects in the interleukin-10 (IL-10) signaling pathway have provided new insights into inflammatory bowel disease (IBD). This study is to reveal whether mutations of IL-10 signaling pathway genes contribute to the phenotypes of IBD. Forty children who were diagnosed with IBD below the age of 10 years were enrolled. We sequenced the genes interleukin-10 receptor A (IL-10RA), IL-10RB and IL-10, and analyzed the clinical characteristics of very early-onset IBD (VEO-IBD). In total, 14 out of the 40 children developed their symptoms within 1 year of age. We found mutations in IL-10RA in 7 out of the 40 children (17.5%). All seven children had developed symptoms within the first year of life. Particularly, half of the children with infantile-onset IBD had IL-10RA mutations. None of the remaining 26 children diagnosed above 1 year of age had IL-10RA mutations. No mutations were found in IL-10RB and IL-10. Identified IL-10RA mutations were p.(R101W), p.(Y91C), p.(R262C), p.(R117H) and p.(W69R). IL-10RA mutations were associated with onset of infancy (P<0.001), perianal fistulae (P<0.001), poor response to medical management (P=0.017) and early surgical interventions (P<0.001). VEO-IBD in infancy is phenotypically and genetically different disease entity from adult-onset or older child-onset IBD. It has a strong association with IL-10 receptor gene. We should consider the genotyping of genes of the IL-10 signaling pathway including IL-10RA in patients with VEO-IBD, especially in whom with onset of perianal fistulae and severe colitis.

Shim JO. Pediatr Gastroenterol Hepatol Nutr. 2019 Jan;22(1):41-49. https://doi.org/10.5223/pghn.2019.22.1.41

Lee JH, et al. Pediatr Gastroenterol Hepatol Nutr. 2016 Mar;19(1):20-28. http://dx.doi.org/10.5223/pghn.2016.19.1.20

Shim JO. Pediatr Gastroenterol Hepatol Nutr. 2013 Mar;16(1):17-21. http://dx.doi.org/10.5223/pghn.2013.16.1.17

The gut covers a large surface area of the body and faces various external factors. The brain works in concert with commensal microbes in the gut to efficiently process the enormous amount of chemical signals that enter the gut every day. This review discusses: (1) evidence that gut bacteria can alter brain development and behavior, (2) mechanisms by which gut bacteria communicate with the brain, (3) preclinical and clinical studies demonstrating the impact of gut microbiota on autism spectrum disorder, and (4) variables worth consideration by future research on gut bacteria.