Intestinal microbiota control acute kidney injury severity by immune modulation.

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.

• Authors: Jihyun Yang, Chan Johng Kim, Yoon Sook Go, Hee Young Lee, Myung-Gyu Kim, Se Won Oh, Won Yong Cho, Sin-Hyeog Im, Sang Kyung Jo
• Journal: Kidney international (Kidney Int) Vol. 98 Issue 4 Pg. 932-946 (10 2020) ISSN: 1523-1755 [Electronic] United States
• PMID: 32470493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Topics

• Acute Kidney Injury (prevention & control)
• Animals
• Gastrointestinal Microbiome
• Immunity
• Kidney
• Mice
• Reperfusion Injury (prevention & control)