Estudo do eixo intestino-rim: as alterações na microbiota intestinal em um modelo experimental de nefropatia induzida pela adriamicina

• Autor(a) principal: Silva, Denis Goncalves [UNIFESP]
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6308717; https://repositorio.unifesp.br/handle/11600/53181
• topic: Kidney diseases; Glomerulopathies; Podocytes; Doenças renais; Glomerulopatias; Podócitos; Nefropatia induzida pela adriamicina; Adriamicina; Microbiota

Introduction: Kidney diseases are a global epidemic, with a high economic burden for global health systems. Recently, the gut-kidney axis is gaining strength as organs that influence each other, however little is known on how glomerulopathies, as Focal segmental glomerulosclerosis (FSGS), can modify and affect the composition of the gut microbiota and metabolites. The progressive loss of podocytes is a major cause of chronic kidney disease (CKD), with a high prevalence rate and limited current etiological knowledge. Objective: Explore the interrelationship between the renal injury caused by glomerular dysfunction and changes in gut microbiota. Methods: Wild type Balb/c mice were chemically-induced to develop glomerulopathy (Adriamycin, ADR) and were evaluated for 30 days. In parallel, 14 days before receiving ADR, a group of Balb/c mice underwent microbiota depletion, administering broad spectrum antibiotics (ampicillin, metronidazole, neomycin, vancomycin) in autoclaved drinking water and then they were induced the same way to develop glomerulopathy. Results: ADR caused renal histopathological lesions, such as glomerular collapse, decreased number of podocytes per glomerulus, glomerular barrier dysfunction and uremia. In addition, ADR-induced animals showed histological changes in gut colon, with increased levels in amorphous cell mass and a decrease in claudin-1 expression. Structural changes in intestinal colon were also associated with gut microbiota dysbiosis, with reduced Bacteroidetes phylum and less gut mucus. Disease-induced animals that had previously depleted gut microbiota exhibited better glomerular barrier function, with lower levels of protein and albumin in the urine. Conclusion: Our results shows, for the first time in literature, that the development of ADR-induced glomerulopathy promotes changes in the structure of the colon and in the proportion of gut bacterial phyla. Interestingly, initial results showed that depletion of gut microbiota conferred protection to the loss of glomerular barrier function.