PhD defense :

Mechanisms of microbiome adaptation to chronic exposure to xenobiotics and its impact on secondary treatment responses.

The increasing use of psychotropic drugs, particularly antiseizure medication, represents an emerging threat to public health due to their potential effects on the gut microbiome. These medications, often administered daily over extended periods of time, can alter the microbiota, yet the impact of chronic exposure remains under-investigated. Understanding these effects is essential, as they may also influence the microbiome’s response to secondary treatments such as antibiotics.

This study aims to evaluate the impact of prolonged antiseizure exposure on the composition, metabolome, and resistome of microcosms derived from the feces of young children, using 16S rRNA gene sequencing, shotgun sequencing, tandem mass spectrometry (UPLC-MS/MS), and RT-qPCR. Additionally, the response of the ASMs pre-exposed microcosms to antibiotic treatments was studied through bacterial growth analysis (optical density) and composition (shotgun sequencing). Finally, the effect of antiepileptics on horizontal gene transfer (conjugation and transformation) was assessed.

Chronic exposure to carbamazepine alters the composition of microcosms, with an increase in the abundance of Escherichia and a decrease in Bacteroides. These changes are associated with modifications in metabolic functions, particularly in the glutamine pathway, and an increase in antibiotic resistance genes, such as efflux pumps. Furthermore, chronic carbamazepine exposure enhances the microbiome’s sensitivity to ampicillin, reducing its diversity, and also appears to promote gene transfer via conjugation among commensal bacteria.

Keywords: Gut microbiota – Antiseizure medication – Antibiotic resistance – Gene transfer – Metabolic function

Jury members:

• Etienne RUPPÉ, Prof. Dr, Université Paris Cité – Rapporteur & Examinateur
• Geneviève HÉRY-ARNAUD, Prof. Dr, Université de Bretagne Occidentale – Rapporteur & Examinatrice
• Imad KANSAU, Prof. Dr, Faculté de Pharmacie, Université Paris-Saclay – Examinateur
• Théodore BOUCHEZ, Dr, Université Paris-Saclay – Examinateur

Directed by:

Patricia Lepage