Species-specific modulation of serotonin-related gene expression by Akkermansia muciniphila, Faecalibacterium prausnitzii, and their extracellular vesicles in HT-29 cells.

Abstract

Background: Host-microbiota interactions play a critical role in modulating the serotonin (5-HT) system, which is essential for maintaining intestinal homeostasis. Akkermansia muciniphila and Faecalibacterium prausnitzii are well-recognized commensal bacteria with anti-inflammatory properties and barrier-enhancing functions. However, their effects on the regulation of serotonin-related gene expression in intestinal epithelial cells remain poorly understood. This study investigated the effects of A. muciniphila and F. prausnitzii, as well as their extracellular vesicles (EVs), on the serotonergic system in the human colorectal adenocarcinoma HT-29 cell line.

Methods and results: HT-29 cells were exposed to viable bacteria and their corresponding EVs, and serotonin levels were quantified using ELISA. In parallel, the expression of genes involved in serotonin signaling and metabolism was evaluated. Although neither bacterial strain significantly altered serotonin levels, treatment with EVs resulted in a significant increase compared with control cells. Furthermore, both bacterial and EV treatments modulated the mRNA expression of key genes associated with serotonergic signaling and metabolic pathways.

Conclusions: Importantly, A. muciniphila and F. prausnitzii exerted distinct effects on serotonin-related pathways, suggesting species-specific regulatory mechanisms. These findings indicate that commensal bacteria and their EVs may represent promising modulators of disorders associated with dysregulated serotonin signaling. Overall, this study provides novel insight into the role of gut microorganisms and their extracellular vesicles in shaping the intestinal serotonergic system.