Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen

Amy Ontai-Brenning1,2, Randy Hamchand3,4, Jason M Crawford2,3,4

  • 1Microbial Sciences Institute, Yale University, West Haven, Connecticut, USA.

Mbio
|November 16, 2023
PubMed
Abstract

Insights

Mammalian gut microbes use (p)ppGpp signaling to maintain stability during fasting periods. Disrupting this response impairs microbial colonization, impacting host health and microbiome interactions.

Area of Science:

  • Microbiology
  • Host-Microbiome Interactions
  • Physiology

Background:

  • Mammalian feeding patterns create a fluctuating gut environment.
  • This dynamic environment impacts host-microbiome interactions, immunity, and health.
  • Gut microbes must adapt to these feeding-fasting cycles.

Purpose of the Study:

  • To investigate microbial adaptive responses to time-restricted feeding.
  • To identify molecular mechanisms enabling gut microbes to withstand fasting periods.
  • To understand the role of microbial signaling in maintaining gut microbiome stability.

Main Methods:

  • Utilized mouse models with time-restricted feeding regimens.
  • Measured intracellular signaling molecule levels ((p)ppGpp) in gut microbes.
  • Genetically modified a human gut commensal to disable the (p)ppGpp response.
  • Assessed microbial colonization during host fasting phases.

Main Results:

  • Gut microbes elevate (p)ppGpp levels during the fasting phase of time-restricted feeding.
  • Disabling the (p)ppGpp response significantly reduced microbial colonization in the fasting host.
  • This microbial response is conserved across species and within mammalian gut communities.

Conclusions:

  • The (p)ppGpp signaling pathway is crucial for gut microbiome stability during host fasting.
  • This mechanism allows healthy gut microbiomes to adapt to fluctuating feeding environments.
  • Targeting this pathway may offer insights into modulating host-microbiome interactions and health.

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