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From Gut Homeostasis to Colorectal Cancer: Spatial and Temporal Reprogramming of Microbial Inosine Signaling.

Lorenzo Tomassini1, Teresa Pacifico1, Giovanni Monteleone1,2

  • 1Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.

Biomedicines
|May 27, 2026
PubMed
Summary
This summary is machine-generated.

Inosine, a microbial metabolite, plays a dual role in gut health and colorectal cancer (CRC). It supports gut homeostasis but can promote CRC, shifting to anti-tumor immunity by modulating T cells and macrophages.

Keywords:
T cell activationadenosinecolitis-associated cancergut microbiotaimmunotherapyintestinal homeostasismicrobial metabolitesmicrobiota–host interactionspurinetumor microenvironment

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Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Microbial metabolites critically regulate gut homeostasis and host-immune interactions.
  • Inosine, a bioactive purine metabolite, influences intestinal barrier integrity and immune responses.
  • Its function is altered in conditions like chronic inflammation, dysbiosis, and colorectal cancer (CRC).

Purpose of the Study:

  • To review the biochemical properties, signaling, and sources of inosine.
  • To elucidate inosine's role in maintaining gut homeostasis.
  • To discuss inosine's dynamic regulation of host-microbiota interactions during CRC development and progression.

Main Methods:

  • Literature review of inosine's biochemical properties and signaling pathways.
  • Analysis of inosine's role in gut homeostasis and immune modulation.
  • Examination of inosine's spatial and temporal reprogramming in CRC.

Main Results:

  • Inosine supports intestinal barrier integrity and modulates immune responses under physiological conditions.
  • During CRC, inosine's distribution and function are altered, potentially shifting from tumor-supportive to anti-tumor roles.
  • Inosine influences T cell function and macrophage polarization, impacting host-microbiota crosstalk.

Conclusions:

  • Inosine is a critical modulator of host-microbiota crosstalk in both health and disease.
  • Inosine exhibits context-dependent functions, shifting from promoting CRC to triggering anti-tumor immunity.
  • Inosine represents a promising therapeutic target for microbiome-based strategies and combined clinical approaches in CRC treatment.