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Neuronal programming by microbiota enables environmental regulation of intestinal motility

By Yuuki Obata, Stefan Boeing, Álvaro Castaño, Ana Carina Bon-Frauches, Mercedes Gomez de Agüero, Werend Boesmans, Bahtiyar Yilmaz, Rita Lopes, Almaz Huseynova, Muralidhara Rao Maradana, Pieter Vanden Berghe, Andrew J Murray, Brigitta Stockinger, Andrew J. Macpherson, Vassilis Pachnis

Posted 15 Mar 2019
bioRxiv DOI: 10.1101/579250 (published DOI: 10.1038/s41586-020-1975-8)

Environmental signals modulate the activity of the nervous system and harmonize its output with the outside world. Synaptic activity is crucial for integrating sensory and effector neural pathways but the role of transcriptional mechanisms as environmental sensors in the nervous system remains unclear. By combining a novel strategy for transcriptomic profiling of enteric neurons with microbiota manipulation, we demonstrate that the transcriptional programs of intestinal neural circuits depend on their anatomical and physiological context. We also identify the ligand-dependent transcription factor Aryl hydrocarbon Receptor (AhR) is an intrinsic regulator of enteric nervous system output. AhR is instated as a neuronal biosensor in response to microbiota colonization allowing resident enteric neurons to directly monitor and respond to the intestinal microenvironment. We suggest that AhR signaling integrates neuronal activity with host defence mechanisms towards gut homeostasis and health.

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