title: Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion.
abstract: Short-chain fatty acids (SCFAs) are fermentation end products produced by the intestinal microbiota and have anti-inflammatory and histone deacetylase-inhibiting properties. Recently, a dual relationship between the intestine and kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI model in which the inflammatory process has a detrimental role. We observed that therapy with the three main SCFAs (acetate, propionate, and butyrate) improved renal dysfunction caused by injury. This protection was associated with low levels of local and systemic inflammation, oxidative cellular stress, cell infiltration/activation, and apoptosis. However, it was also associated with an increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and modulated the expression levels of enzymes involved in chromatin modification. In vitro analyses showed that SCFAs modulated the inflammatory process, decreasing the maturation of dendritic cells and inhibiting the capacity of these cells to induce CD4(+) and CD8(+) T cell proliferation. Furthermore, SCFAs ameliorated the effects of hypoxia in kidney epithelial cells by improving mitochondrial biogenesis. Notably, mice treated with acetate-producing bacteria also had better outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and viability after an injury through modulation of the inflammatory process, most likely via epigenetic modification.
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Vinicius
authors.initials: V
authors.lastname: Andrade-Oliveira
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Mariane T
authors.initials: MT
authors.lastname: Amano
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Matheus
authors.initials: M
authors.lastname: Correa-Costa
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Angela
authors.initials: A
authors.lastname: Castoldi
authors.affiliation: Nephrology Division, Federal University of São Paulo, São Paulo, Brazil;
authors.forename: Raphael J F
authors.initials: RJ
authors.lastname: Felizardo
authors.affiliation: Nephrology Division, Federal University of São Paulo, São Paulo, Brazil;
authors.forename: Danilo C
authors.initials: DC
authors.lastname: de Almeida
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Enio J
authors.initials: EJ
authors.lastname: Bassi
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Moraes-Vieira
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Meire I
authors.initials: MI
authors.lastname: Hiyane
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Andrea C D
authors.initials: AC
authors.lastname: Rodas
authors.affiliation: Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Jean P S
authors.initials: JP
authors.lastname: Peron
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;
authors.forename: Cristhiane F
authors.initials: CF
authors.lastname: Aguiar
authors.affiliation: Division of Pathology, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil;
authors.forename: Marlene A
authors.initials: MA
authors.lastname: Reis
authors.affiliation: Department of Pharmacy and Biotechnology, Universidade Anhanguera de São Paulo UNIAN-SP, São Paulo, Brazil;
authors.forename: Willian R
authors.initials: WR
authors.lastname: Ribeiro
authors.affiliation: Department of Pharmacy and Biotechnology, Universidade Anhanguera de São Paulo UNIAN-SP, São Paulo, Brazil;
authors.forename: Claudete J
authors.initials: CJ
authors.lastname: Valduga
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil; and.
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.affiliation: Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas-UNICAMP, São Paulo, Brazil.
authors.forename: Marco Aurelio Ramirez
authors.initials: MA
authors.lastname: Vinolo
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil; and.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Ferreira
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil; Nephrology Division, Federal University of São Paulo, São Paulo, Brazil; niels@icb.usp.br.
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001644:Bifidobacterium; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005232:Fatty Acids, Volatile / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D019936:Probiotics / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D005232:Fatty Acids, Volatile
keywords: SCFA; epigenetic modifications; ischemia-reperfusion; kidney disease; microbiota