Agradecimentos: The authors thank Paulo Albe (Institute of Biomedical Sciences IV, Universidade de São Paulo, São Paulo, Brazil) for preparing the histology slides, Caroline Ang and Linda Mason (both from Biodiscovery Institute, Monash University, Melbourne, Australia) for technical assistance, and...

Agradecimentos: The authors thank Paulo Albe (Institute of Biomedical Sciences IV, Universidade de São Paulo, São Paulo, Brazil) for preparing the histology slides, Caroline Ang and Linda Mason (both from Biodiscovery Institute, Monash University, Melbourne, Australia) for technical assistance, and Centro de Facilidades de Apoio à Pesquisa (CEFAP–USP). This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; Grants 2012/15205‐4, 2012/50410‐8, 2012/02270‐2, 2014/13135‐4, 2017/06222‐06, and 2017/05264‐7), Conselho Nacional de Desenvolvimento Científico e Tecnológico, (CNPq), Instituto Nacional de Ciência e Tecnologia (INCT) REGENERA, and the National Health and Medical Research Council of Australia. This study was also financed, in part, by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES), Finance Code 001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no conflicts of interest

Butyrate is a short-chain fatty acid derived from the metabolism of indigestible carbohydrates by the gut microbiota. Butyrate contributes to gut homeostasis, but it may also control inflammatory responses and host physiology in other tissues. Butyrate inhibits histone deacetylases, thereby...

Butyrate is a short-chain fatty acid derived from the metabolism of indigestible carbohydrates by the gut microbiota. Butyrate contributes to gut homeostasis, but it may also control inflammatory responses and host physiology in other tissues. Butyrate inhibits histone deacetylases, thereby affecting gene transcription, and also signals through the metabolite-sensing G protein receptor (GPR)109a. We produced an mAb to mouse GPR109a and found high expression on podocytes in the kidney. Wild-type and Gpr109a(-/-) mice were induced to develop nephropathy by a single injection of Adriamycin and treated with sodium butyrate or high butyrate-releasing high-amylose maize starch diet. Butyrate improved proteinuria by preserving podocyte at glomerular basement membrane and attenuated glomerulosclerosis and tissue inflammation. This protective phenotype was associated with increased podocyte-related proteins and a normalized pattern of acetylation and methylation at promoter sites of genes essential for podocyte function. We found that GPR109a is expressed by podocytes, and the use of Gpr109a(-/-) mice showed that the protective effects of butyrate depended on GPR109a expression. A prebiotic diet that releases high amounts of butyrate also proved highly effective for protection against kidney disease. Butyrate and GPR109a play a role in the pathogenesis of kidney disease and provide one of the important molecular connections between diet, the gut microbiota, and kidney disease

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP

2012/15205-4; 2012/50410-8; 2012/02270-2; 2014/13135-4; 2017/06222-06; 2017/05264-7

COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ

001

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