Exposure to anti-seizure medications impact growth of gut bacterial species and subsequent host response
2022
Ilhan, Zehra Esra | Brochard, Vincent | Lapaque, Nicolas | Auvin, Stéphane | Lepage, Patricia | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité) | AP-HP Hôpital universitaire Robert-Debré [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Institut universitaire de France (IUF) ; Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.) | ANR-19-CE17-0033,TrilliAED,Le microbiome intestinal associé à la réponse aux anti-épileptiques chez les enfants épileptiques(2019)
International audience
Afficher plus [+] Moins [-]anglais. Anti-seizure medications (ASMs) are the first line of treatment for seizure control in children with epilepsy. Cumulative evidence suggests an imbalanced gut microbiota in refractory epilepsy patients. We systematically investigated the differential antimicrobial impacts of nine ASM active ingredients, seven common excipients of ASMs, and four syrup formulations on core early-life gut microbiota strains. Additionally, we evaluated the toxicity and gene expression profiles of HT-29 colon epithelial cells when exposed to active ingredients with or without bacterial supernatants. The physicochemical structure of ASM active ingredients and bacterial phylogeny were found to be related to ASM toxicity. Carbamazepine, lamotrigine, and topiramate reduced the growth of more than ten strains along with syrup excipient propyl-paraben. Various artificial sweeteners present in ASM formulations stimulated the growth of gut bacterial strains. The active ingredients that were more toxic to bacterial strains also exhibited toxicity towards HT-29 cells, yet Bifidobacterium longum supernatant reduced cytotoxic effects of carbamazepine and lamotrigine. Akkermansia muciniphila or mixed community supernatants reduced the expression of drug resistance genes in HT-29 cell lines. In summary, our results indicate that several ASM active ingredients and their excipients regulate the growth of gut bacterial strains in a species-specific manner. Interactions between ASMs and gut epithelial cells might be modulated by gut microbial metabolites.
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