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Dual roles of commensal bacteria after intestinal ischemia and reperfusion

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Abstract

Purpose

The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR.

Methods

Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated.

Results

Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation.

Conclusions

Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (nos. 81200266 and 81270441).

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Authors and Affiliations

  1. Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China

    Hong-yi Zhang, Xuyong Chen, Xinrao Meng & Jie-xiong Feng

  2. Department of Neurology, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430014, China

    Fang Wang

  3. Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Chenzhao Feng

Authors
  1. Hong-yi Zhang
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  2. Fang Wang
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  3. Xuyong Chen
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  4. Xinrao Meng
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  6. Jie-xiong Feng
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Correspondence to Jie-xiong Feng.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Zhang, Hy., Wang, F., Chen, X. et al. Dual roles of commensal bacteria after intestinal ischemia and reperfusion. Pediatr Surg Int 36, 81–91 (2020). https://doi.org/10.1007/s00383-019-04555-5

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