Antiepileptics influence gut microbiota: a possible relationship with drug-resistance?

Specific pathways linking the microbial community inhabiting our gastrointestinal tract with the central nervous system have been suggested. Indeed, the role of gut microbiota (GM), with its influence on immune mechanisms in patients with chronic neurological diseases, has recently been highlighted to be related to many of them. While there is a very small amount of studies unraveling GM composition in epileptic patients, it has been highlighted how the microbiota can alter the progression of epilepsy, in particular by modulating the release of proinflammatory cytokines. Approximately one third of patients, despite the numerous pharmacological therapies available, show drug resistance; it is, therefore, important to look for new complementary therapeutic strategies that can influence the clinical picture. This study aims to observe possible drug-driven gut community changes by characterizing pre- and post- antiepileptic drug GM. Here we present preliminary results conducted on a dataset of 10 samples collected from 5 children affected by epilepsy, comparing their naive GM before the therapy (“naive microbiome”, NM) and after taking for at least 4 months (“in therapy”, IT) one of the most common antiepileptic drugs (Valproate, Levetiracetam, Ethosuximide). Bacterial genome was extracted from fecal samples, sequenced via Illumina MiSeq platform and analyzed through QIIME software and specific bioinformatic pipelines. Overall results suggest an increased amount of Bacteroides and Faecalibacterium spp. during the therapy (respectively, from NM to IT status: 27.8 to 30.3%; 8.7 to 10.0%), while drug assumption seems to be related to a smaller quantity of Roseburia, Ruminococcus and Akkermansia spp (5.1 to 4.5%; 6 to 2.4%; 3.7 to 0.2% in NM and IT subjects, respectively). For each pair of samples of the patients (NM vs IT), we observed a common decrease of Ruminococcus and Oscillospira spp. during the assumption of the drug. While Roseburia produces short-chain fatty acids (butyrate, in particular) and Akkermansia contributes to strengthen intestinal walls, Ruminococcus and Oscillospira help resistant starches digestion and fermentation: the decrease in the amount of these beneficial genera may indicate a dysbiosis occurring during the patients’ drug assumption. These preliminary results suggest that drugs other than antibiotics could impact on gut microbiota and that they should be considered as possible environmental factors modifying the microbial community. The observed changes, in turn, might influence host response to therapy.