Abstract: TH-PO280

AKI Increases Gut Permeability and Provokes Dysregulation of Mucosal Immunity: Effect of Probiotics on AKI Severity

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Yang, Jihyun, Korea University Hospital, Seoul, Korea (the Republic of)
  • Choi, Yoon kyung, Korea University Hospital, Seoul, Korea (the Republic of)
  • Hwang, Taeyeon, Korea University Hospital, Seoul, Korea (the Republic of)
  • Cho, Woori Crystal, Korea University hospital, Seoul, Korea (the Republic of)
  • Kim, Myung-gyu, National Institutes of Health , North Bethesda, Maryland, United States
  • Cho, Won-Yong, Korea University Hospital, Seoul, Korea (the Republic of)
  • Jo, Sang-Kyung, Korea University Hospital, Seoul, Korea (the Republic of)
Background

.Emerging evidence indicate the presence of kidney-gut crosstalk in diverse pathological conditions. In normal condition, healthy microbiome help to maintain gut barrier and mucosal immune tolerance. In this study, we investigated kidney-gut crosstalk in AKI by assessing the effect of AKI on gut barrier integrity and mucosal immunity.

Methods

C57BL/6 mice underwent bilateral ischemia-reperfusion injury (IRI) or sham operation. In the probiotic treatment group, Bifidobacillus was administered via oral gavage once daily, started 3 weeks prior to the injury. The gut barrier integrity was assessed by measuring orally administered fluorescein isothiocyanate-dextran (FITC-dextran) activity in blood and western blot for various tight junction proteins was performed. Flow cytometric analysis of colonic macrophages as well as Foxp3 expression was performed.

Results

Following AKI, gut permeability increased significantly and it was accompanied by decreased claudin-1, occludin expression and increased number of apoptosis in colon. Ly6G+ neutrophil infiltration and MPO activity increased after kidney IRI and the number of Ly6Chigh CX3CR1.intermediate macrophages also increased. Colonic Foxp3 mRNA expression showed a slight but statistically significant increase. Preconditioning with probiotics prior to IRI significantly attenuated functional, histological kidney injury and the renoprotective effect was accompanied by partial restoration of claudin-1, occludin expression and also by decreased number of colon epithelial cell apoptosis. Colon Foxp3 expression significantly increased in probiotic treated group

Conclusion

In conclusion, AKI induced gut barrier disruption and colonic inflammation might be one mechanism leading to systemic inflammation, kidney and other remote organ injury. Probiotic mediated renoprotective effect might be mediated by strengthening gut barrier and also mucosal immune tolerance mechanisms. Probiotics might be one promising strategy aiming for reducing AKI severity or remote organ injury.