Human Adult Microbiota in a Static Colon Model: AhR Transcriptional Activity at the Crossroads of Host-Microbe Interaction.

Abstract

Functional symbiotic intestinal microbiota regulates immune defense and the metabolic processing of xenobiotics in the host. The aryl hydrocarbon receptor (AhR) is one of the transcription factors mediating host–microbe interaction. An in vitro static simulation of the human colon was used in this work to analyze the evolution of bacterial populations, the microbial metabolic output, and the potential induction of AhR transcriptional activity in healthy gut ecosystems. Fifteen target taxa were explored by qPCR, and the metabolic content was chromatographically profiled using SPME-GC-MS and UPLC-FLD to quantify short-chain fatty acids (SCFA) and biogenic amines, respectively. Over 72 h of fermentation, the microbiota and most produced metabolites remained stable. Fermentation supernatant induced AhR transcription in two of the three reporter gene cell lines (T47D, HepG2, HT29) evaluated. Mammary and intestinal cells were more sensitive to microbiota metabolic production, which showed greater AhR agonism than the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) used as a positive control. Some of the SCFA and biogenic amines identified could crucially contribute to the potent AhR induction of the fermentation products. As a fundamental pathway mediating human intestinal homeostasis and as a sensor for several microbial metabolites, AhR activation might be a useful endpoint to include in studies of the gut microbiota.