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Communication Dans Un Congrès Année : 2023

Chronic exposure to antiseizure drugs impacts the gut microbiome community and function

Résumé

Gut microbiota plays an essential role in the health and the development of the host. Diet and drugs are significant environmental factors affecting the microbiota composition. Exposure to drugs may lead to gut microbial dysbiosis. While the impact of some drugs, such as antibiotics, on the gut microbiome is widely recognized, the influence of chronically administered host-targeted drugs on the gut microbiome is less known. Our goal was to explore in vitro effects of chronic exposure to three antiseizure drugs (carbamazepine, valproate, and levetiracetam) on the gut microbial composition and metabolic functions. Microcosms were established by cultivating four fecal inoculums from young children (11 months to 4 yo) over 24 hours. Using a semi-batch process, these fecal-derived microcosms were cultivated for 11 cycles (24 hours each) with the three antiseizure drugs or drug-free controls; the first seven cycles with daily transfer to fresh media containing 2mM of the drugs, followed by four cycles of potential recovery period without any drugs. The impact of this exposure on the microbial community dynamics (diversity and composition) was determined by 16S rRNA gene sequencing of cycle 1 and 7 cultures. Metabolism of the microbial community after cycles 1 and 7 of exposure to carbamazepine was evaluated by a non-targeted metabolomics approach (LC-MS). Our results show that semi-continuous cultivation strategy changed the overall microcosm composition during the first seven cycles until reaching a steady state. Carbamazepine had the most substantial impact on the gut microbiota structure and metabolism. More specifically, 9 genera including Murimonas and Clostridium XIVa were positively influenced by the carbamazepine exposure and 6 genera were negatively influenced such as Faecalibacterium and Gemmiger . We also observed that microbiome composition partially recovered after the four drug-free cycles. Finally, longitudinal exposure to carbamazepine modified the metabolic function of the microcosms by decreasing 52 metabolites that belong to Amino Acid, Carbohydrate, Cofactors and Vitamins Lipid, Energy, Nucleotide, Peptide and Xenobiotics super-pathways. Understanding the longitudinal impact of antiseizure drugs on the gut microbiota may help develop modulation strategies to mitigate the treatment consequences on the gut microbiota and subsequently for the host health.
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Dates et versions

hal-04296650 , version 1 (22-11-2023)

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  • HAL Id : hal-04296650 , version 1

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Camille Dop, Stéphane Auvin, Patricia Lepage, Zehra Esra Ilhan. Chronic exposure to antiseizure drugs impacts the gut microbiome community and function. 15TH SEEON CONFERENCE, Jun 2023, Seeon Monastery, Germany, Germany. ⟨hal-04296650⟩
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