Nature | Vol 578 | 13 February 2020 | 289that regulate neuronal excitability (Kcnj12) as a class of AHR signalling
targets provides a plausible molecular link between the dynamic micro-
environment of the gut lumen and the functional output of intestinal
neural circuits. Although the full spectrum and detailed molecular
mechanisms that act downstream of neuronal AHR remain to be charac-
terized, our experiments suggest that components of this pathway are
implicated in the pathogenesis of intestinal motility disorders. A recent
study has suggested a role for AHR in the biology of stool frequency,
changes of which are one of the hallmarks of irritable bowel syndrome^28.
Therefore, pharmacological or dietary interventions that modulate
AHR activity in the cellular circuitry that controls intestinal peristalsis
offer a realistic strategy for the management of conditions associated
with gut dysmotility. In addition to the role of AHR in neurogenic motil-
ity, AHR-dependent transcriptional programs are also central to the
barrier function of intestinal epithelial cells and the mucosal immune
system^25 ,^29. We suggest that, by transmitting environmental triggers
within diverse cell types, AHR integrates the activity of functionally
distinct intestinal tissues towards gut homeostasis and host defence.
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availability are available at https://doi.org/10.1038/s41586-020-1975-8.
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