Related Experiment Video
Updated: Aug 12, 2026
08:50
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Immunometabolic Modulation by Low-Dose Sodium Butyrate: PI3K/Akt/mTOR Signalling Orchestrates Macrophage Polarization
Sisi Zhang1,2,3, Zhou Jingxiang1,2,3, Caixia Tan1,2,3
1Department of Infection Control Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Immunology
|August 11, 2026
Summary
Sodium butyrate (NaB) alleviates Clostridioides difficile infection (CDI) by promoting anti-inflammatory M2 macrophages and enhancing epithelial repair. This host-directed therapy targets PI3K/Akt/mTOR signaling for improved gut barrier function.
Area of Science:
- Gastroenterology and Immunology
- Microbiome-Host Interactions
- Molecular Mechanisms of Inflammation
Background:
- Clostridioides difficile infection (CDI) causes severe intestinal inflammation and barrier damage.
- The precise immunological mechanisms of sodium butyrate (NaB), a beneficial short-chain fatty acid, in CDI are not fully understood.
- Investigating NaB's role in modulating immune responses and epithelial repair is crucial for developing new therapies.
Purpose of the Study:
- To elucidate the role of sodium butyrate (NaB) in regulating macrophage polarization and epithelial repair during Clostridioides difficile infection (CDI).
- To explore the underlying molecular pathways, including PI3K/Akt/mTOR signaling, involved in NaB's protective effects.
- To assess the therapeutic potential of NaB as a host-directed strategy for CDI.
Main Methods:
- Utilized murine CDI models, primary and cell line-based macrophages, and Caco-2 epithelial cells.
- Employed macrophage-epithelial co-culture systems to study cell-cell interactions.
- Investigated molecular signaling pathways (PI3K/Akt/mTOR) and cytokine profiles (IL-10, IL-1β) in response to NaB treatment.
Main Results:
- NaB treatment significantly reduced CDI severity, inflammation, and histopathological damage.
- NaB promoted macrophage polarization to an anti-inflammatory M2 phenotype, characterized by increased CD206 and IL-10.
- NaB suppressed PI3K/Akt/mTOR signaling and enhanced epithelial barrier integrity and repair, partly mediated by IL-10 via macrophage-epithelial crosstalk.
Conclusions:
- Low-dose NaB offers protection against CDI-induced intestinal injury by coordinating macrophage polarization and epithelial repair.
- Modulation of PI3K/Akt/mTOR signaling is a key mechanism underlying NaB's therapeutic effects.
- NaB represents a promising host-directed therapeutic agent for CDI, highlighting the importance of microbiota-derived metabolites in immune regulation.
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