한빛사 논문
Jihyun Yang1, Chan Johng Kim2, Yoon Sook Go1, Hee Young Lee1, Myung-Gyu Kim1, Se Won Oh1, Won Yong Cho1, Sin-Hyeog Im2,*, Sang Kyung Jo1,*
1Division of Nephrology, Department of Internal Medicine, Korea University Medical College, Seoul, Korea
2Division of Integrative Biosciences and Biotechnology & Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea
*Correspondence
Abstract
Intestinal microbiota impacts the host immune system and influences the outcomes of chronic diseases. However, it remains uncertain whether acute kidney injury (AKI) impacts intestinal microbiota or vice versa. To determine this, we investigated the mechanistic link between AKI, microbiota, and immune response in ischemia/reperfusion injury. Microbiota alteration and its biological consequences after ischemia/reperfusion injury were examined and the effect of dysbiotic microbiota on the outcome of AKI was also assessed by colonizing germ-free mice with post-AKI microbiota. The role of Th17, Th1, Tregs cells and macrophage polarization in mediating the renoprotective effect of antibiotic induced microbiota depletion in ischemia/reperfusion injury was also determined. Increase of Enterobacteriacea, decrease of Lactobacilli, and Ruminococacceae were found to be the hallmarks of ischemia/reperfusion injury induced dysbiosis and were associated with a decreased levels of short-chain fatty acids, intestinal inflammation and leaky gut. Colonizing germ-free mice with post-AKI microbiota worsened ischemia/reperfusion injury severity with exaggerated inflammation in recipient mice compared to colonizing with microbiota from sham operated mice. Microbiota depletion by oral antibiotics protected against ischemia/reperfusion injury. This renoprotective effect was associated with reduced Th 17, Th 1 response along with expansion of regulatory T cells, and M2 macrophages. Our study demonstrated a unique bidirectional relationship between the kidney and the intestine during AKI. Intestinal dysbiosis, inflammation and leaky gut are consequences of AKI but they also represent an important modifier determining post-AKI severity. Thus, targeting the intestinal microbiota might provide a novel therapeutic strategy in AKI.
Keywords : acute kidney injury; dysbiosis; ischemia/reperfusion; leaky gut; macrophages; short-chain fatty acids; T cells
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