Microbiome modulation after severe acute kidney injury accelerates functional recovery and decreases kidney fibrosis

Authors

Sepideh Gharaie, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Kyungho Lee, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Andrea M. Newman-Rivera, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Jiaojiao Xu, Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Shishir Kumar Patel, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Mahta Gooya, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Lois J. Arend, Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Dominic S. Raj, Department of Medicine, George Washington University, School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Jennifer Pluznick, Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Chirag Parikh, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Sanjeev Noel, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Hamid Rabb, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA. Electronic address: hrabb1@jhmi.edu.

Document Type

Journal Article

Publication Date

9-1-2023

Journal

Kidney international

Volume

104

Issue

3

DOI

10.1016/j.kint.2023.03.024

Keywords

acute kidney injury; amoxicillin; glomerular filtration rate; gut bacteria; kidney repair; microbiome

Abstract

Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included increased glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4T cells, interleukin (IL)-17 CD4T cells, and tumor necrosis factor-α double negative T cells while it increased CD8T cells and PD1CD8T cells. Amoxicillin also increased gut lamina propria CD4T cells while decreasing CD8T and IL-17CD4T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3CD8T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease.

APA Citation

Gharaie, Sepideh; Lee, Kyungho; Newman-Rivera, Andrea M.; Xu, Jiaojiao; Patel, Shishir Kumar; Gooya, Mahta; Arend, Lois J.; Raj, Dominic S.; Pluznick, Jennifer; Parikh, Chirag; Noel, Sanjeev; and Rabb, Hamid, "Microbiome modulation after severe acute kidney injury accelerates functional recovery and decreases kidney fibrosis" (2023). GW Authored Works. Paper 3500.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3500

Department

Medicine