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Probiotics partially attenuate the severity of acute kidney injury through an immunomodulatory effect

Authors
Yang, JihyunJi, Geun EogPark, Myeong SooSeong, Yeong-JeGo, Yoon SookLee, Hee YoungFang, YinaKim, Myung-GyuOh, Se WonCho, Won YongJo, Sang-Kyung
Issue Date
12월-2021
Publisher
KOREAN SOC NEPHROLOGY
Keywords
Acute kidney injury; BGN4; Immunology; Microbiome; Probiotics
Citation
KIDNEY RESEARCH AND CLINICAL PRACTICE, v.40, no.4, pp.620 - 633
Indexed
SCIE
SCOPUS
KCI
Journal Title
KIDNEY RESEARCH AND CLINICAL PRACTICE
Volume
40
Number
4
Start Page
620
End Page
633
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/135653
DOI
10.23876/j.krcp.20.265
ISSN
2211-9132
Abstract
Background: A healthy microbiota helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/ CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and Conclusion: Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.
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