2. Academic Validation
  3. Lactobacillus johnsonii-derived extracellular vesicles carrying GAPDH protect against ulcerative colitis through modulating macrophage polarization

Lactobacillus johnsonii-derived extracellular vesicles carrying GAPDH protect against ulcerative colitis through modulating macrophage polarization

  • J Adv Res. 2025 Jun 16:S2090-1232(25)00444-8. doi: 10.1016/j.jare.2025.06.035.
Shiyu Tao 1,  Mengzhen Song 1,  Jinping Fan 1,  Feng Zhu 2,  Tengfei Lv 3,  Hong Wei 4
Affiliations

Affiliations

  • 1 College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan 430070, China.
  • 2 Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China.
  • 3 Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China. Electronic address: itengfeilv@163.com.
  • 4 College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: weihong63528@163.com.
PMID: 40533059 DOI: 10.1016/j.jare.2025.06.035
Abstract

Introduction: Ulcerative colitis (UC) is a major inflammatory condition worldwide.

Objectives: The purpose of this study was to investigate the potential contribution of Lactobacillus johnsonii against UC from the perspective of gut microbiota-macrophage-host interactions.

Methods: L. johnsonii abundance in UC patients and colitis mice was evaluated by genomic Sequencing. SPF and macrophage-depleted mice were employed to explore the effects of L. johnsonii and its products on colitis. An in vitro macrophage and intestinal epithelial cell co-culture system was constructed. Proteins in extracellular vesicles (EVs) were identified by proteomic analyses, and host signaling pathways were analyzed with transcriptomic analyses.

Results: L. johnsonii abundance was found to be associated with macrophage polarization and intestinal barrier function in human UC patients and mice of a colitis model. L. johnsonii and its derived EVs alleviate colitis in mice in a macrophage-dependent manner. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein in EVs derived from L. johnsonii, counteracts colitis in vitro and in vivo by regulating macrophage phenotype. GAPDH enhances anti-inflammatory macrophage polarization by inhibiting the MAPK-STAT3 axis. Macrophage-secreted EVs enhances intestinal barrier function in colitis mice by blocking the TLR4 pathway. Protein components in macrophage-derived EVs contribute to colitis remission and intestinal barrier protection.

Conclusion: GAPDH originating in L. johnsonii-derived EVs alleviates colitis and improves intestinal barrier by inhibiting STAT3 in macrophages. EVs created from L. johnsonii are a potential novel treatment strategy for UC.

Keywords

Extracellular vesicles; Glyceraldehyde-3-phosphate dehydrogenase; Lactobacillus johnsonii; Macrophage; Ulcerative colitis.

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