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Updated: Dec 29, 2025

An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota
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Neuronal programming by microbiota regulates intestinal physiology.

Yuuki Obata1, Álvaro Castaño2, Stefan Boeing2

  • 1The Francis Crick Institute, London, UK. Yuuki.Obata@crick.ac.uk.

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Summary
This summary is machine-generated.

The aryl hydrocarbon receptor (AHR) acts as a gut sensor in intestinal neurons, linking microbial signals to gut motility. This discovery reveals a key mechanism for maintaining digestive health and homeostasis.

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Area of Science:

  • Neuroscience
  • Gastroenterology
  • Molecular Biology

Background:

  • Neural control of visceral organs is vital for health, with intestinal peristalsis crucial for digestion and defense.
  • Dysregulation of gut motility is common in gastrointestinal disorders, but molecular mechanisms linking luminal factors to neural control are unclear.

Purpose of the Study:

  • To investigate the role of the aryl hydrocarbon receptor (AHR) as a molecular link between the gut microbiota and intestinal neural circuits.
  • To elucidate how AHR signaling in enteric neurons influences gut motility and homeostasis.

Main Methods:

  • Nuclear RNA sequencing of mouse enteric neurons from different intestinal segments and microbiota states.
  • Genetic manipulation of AHR and its regulator CYP1A1 in mouse models.
  • Assessment of intestinal peristaltic activity in response to AHR modulation and antibiotic treatment.

Main Results:

  • Enteric neurons in the colon display unique transcriptional profiles influenced by host genetics and microbial colonization.
  • Microbiota-induced AHR expression in distal enteric neurons allows them to sense the luminal environment and activate effector mechanisms.
  • Neuron-specific AHR deletion or CYP1A1 overexpression reduced colonic peristalsis, mimicking microbiota-depleted states.
  • Restoring AHR expression in enteric neurons of antibiotic-treated mice partially recovered intestinal motility.

Conclusions:

  • The aryl hydrocarbon receptor (AHR) functions as a critical biosensor in intestinal neural circuits, integrating microbial signals with gut function.
  • AHR signaling in enteric neurons represents a key regulatory node for maintaining gut homeostasis and motility.
  • Targeting AHR pathways may offer therapeutic strategies for gastrointestinal disorders characterized by motility dysfunction.