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Updated: Sep 26, 2025

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High-fat diet disrupts REG3γ and gut microbial rhythms promoting metabolic dysfunction.

Katya Frazier1, Amal Kambal1, Elizabeth A Zale2

  • 1Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.

Cell Host & Microbe
|April 19, 2022
PubMed
Summary

Dietary rhythms in gut microbes impact host metabolism. Host Reg3γ peptide and microbes coordinate these rhythms, with high-fat diets disrupting this balance and affecting metabolic health.

Keywords:
Reg3γcircadian rhythmsdiurnal oscillationgerm freegut microbiotahigh-fat diethost-microbe interactionsinnate immunityorganoidsmall intestine

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Area of Science:

  • Microbiology
  • Metabolism
  • Chronobiology

Background:

  • Gut microbial diurnal oscillations are crucial for host circadian rhythms and metabolism.
  • The complex interplay between diet, microbes, and host factors regulating intestinal oscillations is not fully understood.

Purpose of the Study:

  • To investigate the role of host C-type lectin antimicrobial peptide Reg3γ in orchestrating diet-microbe-host interactions in the gut.
  • To understand how high-fat diets disrupt microbial oscillations and impact host metabolic homeostasis.

Main Methods:

  • Utilized a mouse model to study gut microbial and host factor dynamics.
  • Analyzed the relationship between diet, host Reg3γ expression, and gut microbial oscillations.

Main Results:

  • Host Reg3γ peptide and specific ileal microbes bidirectionally orchestrate gut rhythms independently of the core circadian clock.
  • High-fat diets primarily drive microbial oscillations that impair host metabolic homeostasis.
  • Arrhythmic host Reg3γ expression, driven by high-fat diets, secondarily affects microbial abundance and oscillations.

Conclusions:

  • Transkingdom coordination of biological rhythms is significantly influenced by diet and reciprocal host-microbial signals.
  • Restoring the gut microbiota's ability to sense dietary signals via host factors like Reg3γ may improve metabolic dysfunction.