title: Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion Injury.
abstract: An accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gut microbiota with broad-spectrum antibiotics and performed renal ischemia-reperfusion (I/R) injury in mice. Depletion of the microbiota significantly attenuated renal damage, dysfunction, and remote organ injury and maintained tubular integrity after renal I/R injury. Gut flora-depleted mice expressed lower levels of F4/80 and chemokine receptors CX3CR1 and CCR2 in the F4/80+renal resident macrophage population and bone marrow (BM) monocytes than did control mice. Additionally, compared with control BM monocytes, BM monocytes from gut flora-depleted mice had decreased migratory capacity toward CX3CL1 and CCL2 ligands. To study whether these effects were driven by depletion of the microbiota, we performed fecal transplants in antibiotic-treated mice and found that transplant of fecal material from an untreated mouse abolished the protective effect of microbiota depletion upon renal I/R injury. In conclusion, we show that depletion of gut microbiota profoundly protects against renal I/R injury by reducing maturation status of F4/80+renal resident macrophages and BM monocytes. Therefore, dampening the inflammatory response by targeting microbiota-derived mediators might be a promising therapy against I/R injury.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and d.emal@amc.uva.nl.
authors.forename: Diba
authors.initials: D
authors.lastname: Emal
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Elena
authors.initials: E
authors.lastname: Rampanelli
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stroo
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Loes M
authors.initials: LM
authors.lastname: Butter
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Gwendoline J
authors.initials: GJ
authors.lastname: Teske
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Geurt
authors.initials: G
authors.lastname: Stokman
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.|Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dessing
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000073883:CX3C Chemokine Receptor 1; D004815:Epidermal Growth Factor / Q000502:physiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply*; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000502:physiology; D015427:Reperfusion Injury / Q000382:microbiology* / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; C464944:Emr4 protein, mouse; D019707:Receptors, Chemokine; D004815:Epidermal Growth Factor
keywords: immunology; ischemia-reperfusion; macrophages