Gut Bacteria Products Prevent AKI Induced by... : Journal of the American Society of Nephrology (original) (raw)

Basic Research

Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion

Andrade-Oliveira, Vinicius*; Amano, Mariane T.*; Correa-Costa, Matheus*; Castoldi, Angela*; Felizardo, Raphael J.F.†; de Almeida, Danilo C.†; Bassi, Enio J.*; Moraes-Vieira, Pedro M.*; Hiyane, Meire I.*; Rodas, Andrea C.D.*; Peron, Jean P.S.‡; Aguiar, Cristhiane F.*; Reis, Marlene A.§; Ribeiro, Willian R.‖; Valduga, Claudete J.‖; Curi, Rui¶; Vinolo, Marco Aurelio Ramirez**; Ferreira, Caroline M.¶; Câmara, Niels Olsen Saraiva*,†

*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;

‡Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil;

§Division of Pathology, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil;

‖Department of Pharmacy and Biotechnology, Universidade Anhanguera de São Paulo UNIAN-SP, São Paulo, Brazil;

¶Department of Physiology and Biophysics, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil; and

**Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas-UNICAMP, São Paulo, Brazil

Correspondence: Dr. Niels Olsen Saraiva Câmara, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1730 Cid. Universitaria, São Paulo 05508-000, Brazil. Email: [email protected]

Received March 19, 2014

Accepted October 2, 2014

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.