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Related Experiment Video

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Engineering a Cortisol Sensing Enteric Probiotic.

Vaughn Litteral1,2, Rebecca Migliozzi1,2, David Metzger1,2

  • 1UES Corporation, 4401 Dayton-Xenia Avenue, Beavercreek, Ohio 45432-1805, United States.

ACS Biomaterials Science & Engineering
|August 30, 2023
PubMed
Summary

Engineered gut bacteria can sense and respond to stress hormone cortisol. This smart probiotic produces mood-boosting compounds, potentially alleviating anxiety and depression while lowering cortisol levels.

Keywords:
5-HT5-alpha-tetrahydrocortisolClostridium scindensEcNEscherichia coli Nissle 1917adrenalbacterial sensorbacterial targeted gene integrationbiosensorchronic stresscortisolengineered probioticglucocorticoidgut brain axislysR transcription factorprobioticssense and respond circuitserotoninsmart probiotictryptaminetryptophantryptophan decarboxylase

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Area of Science:

  • Microbiology
  • Endocrinology
  • Synthetic Biology

Background:

  • Chronic stress elevates cortisol, contributing to various health issues like anxiety and metabolic syndrome.
  • Gut microbiota interactions with endocrine hormones offer potential therapeutic targets.
  • Clostridium scindens exhibits transcriptional responses to cortisol.

Purpose of the Study:

  • To engineer a novel probiotic sensor for real-time cortisol monitoring.
  • To develop a 'smart probiotic' capable of responding to elevated cortisol levels.
  • To investigate the potential of engineered probiotics in modulating the gut-brain axis.

Main Methods:

  • Cortisol-responsive genetic elements from C. scindens were integrated into E. coli Nissle 1917.
  • Engineered bacteria were designed to express a fluorescent reporter for cortisol detection.
  • Further engineering introduced tryptophan decarboxylase to produce tryptamine and serotonin in response to cortisol.

Main Results:

  • A robust cortisol probiotic sensor was successfully designed, tested, and built.
  • The engineered probiotic demonstrated increased sensitivity to cortisol.
  • Treatment with cortisol led to measurable tryptamine production by the smart probiotic.

Conclusions:

  • Engineered probiotics can serve as a model for sense-and-respond systems.
  • This smart probiotic has the potential to improve mood and reduce stress by producing neuromodulators.
  • This approach offers a novel strategy for modulating the gut-brain axis and managing stress-related disorders.