Efeito do uso da farinha de banana verde sobre toxinas urêmicas derivadas do metabolismo da microbiota intestinal em pacientes em diálise peritoneal
Data
2020-06-24
Autores
Andrade, Laila Santos De [UNIFESP]
Orientadores
Valle, Lilian Cuppari [UNIFESP]
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: Vários metabólitos derivados do metabolismo microbiano compõem o metaboloma sérico dos mamíferos, tais como o indoxil sulfato (IS), p-cresil sulfato (pCS) e o ácido indol 3-acético (IAA). Na doença renal crônica (DRC), o acúmulo destes metabólitos tem sido associado à inflamação, doença cardiovascular e mortalidade por todas as causas. Nesse contexto, a fim de atenuar o acúmulo destes metabólitos, os prebióticos surgem como uma possível estratégia. Objetivos: Avaliar o efeito da farinha de banana verde (FBV- 48% de amido resistente) sobre os níveis séricos de IS, pCS, IAA, marcadores inflamatórios (IL-6, TNF-α, IL-10 e PCR), permeabilidade intestinal e sintomas gastrointestinais em indivíduos em programa de diálise peritoneal (DP). Metodologia: Trata-se de um ensaio clínico randomizado, controlado por placebo, duplo-cego, cruzado. Quarenta e três indivíduos em DP foram alocados para o grupo FBV (21 g/dia) ou placebo (amido de milho ceroso- 12 g/dia), por 4 semanas. Após a conclusão deste período, os participantes passaram por um período de washout de 4 semanas e na sequencia utilizaram o suplemento oposto. As concentrações de IS, pCS e IAA foram determinadas por cromatografia líquida de alta performance (HPLC); os níveis séricos de IL-6, TNF-α, IL-10 foram determinados pela tecnologia xMAP da Luminex®; a permeabilidade intestinal foi avaliada por meio da dosagem de endotoxinas no soro; os sintomas gastrointestinais por meio da Escala de Avaliação de Sintomas Gastrointestinais (GSRS) e a ingestão dietética por meio do registro alimentar de três dias alternados. Resultados: Dos 43 pacientes incluídos, 26 completaram o estudo [idade= 55±12 anos; homens- 53,8%; diabetes- 34,6%; diurese residual- 84,6%; tempo em diálise peritoneal= 16 (5-31) meses]. A FBV não promoveu mudanças nos níveis séricos de IS (p=0,70), pCS (p=0,70) e IAA (p=0,74). Uma redução no nível sérico de IS foi observada em um subgrupo de participantes que apresentaram uma ingestão diária de FBV mais próxima da dose proposta no protocolo de estudo [n=11; placebo: mediana 79,5 μmol/L (31-142) versus FBV: 62,5 μmol/L (31-133), p= 0,009]. Dentre os períodos do estudo, nenhuma diferença foi observada na ingestão alimentar habitual, na excreção urinária dos metabólitos estudados, assim como na remoção dos mesmos pelo processo dialítico. Nenhuma diferença foi encontrada nos demais parâmetros analisados. Conclusão: A FBV não afetou os níveis séricos de IS, pCS e IAA. Apenas no subgrupo de participantes que tiveram uma ingestão diária de FBV próxima da dose proposta no estudo foi observada redução no IS.
Introduction: Gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS) and indole 3-acetic acid (IAA), are part of the mammalian serum metabolome. In chronic kidney disease (CKD), the accumulation of these metabolites has been associated to inflammation, cardiovascular disease and mortality from all causes. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating gut microbiota and production of their metabolites. Objectives: To evaluate the effect of unripe banana flour (UBF- 48% of resistant starch, a prebiotic) on serum concentrations of IS, pCS and IAA and on serum inflammatory biomarkers (IL-6, TNF-α, IL-10 e CRP), intestinal permeability and gastrointestinal symptoms in individuals undergoing peritoneal dialysis (PD). Methods: A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch- 12 g/day) for 4 weeks, or vice versa. Between both interventions there was a 4-week washout. Serun concentration of IS, pCS and IAA was determined by high performance liquid chromatography (HPLC); serum levels of IL-6, TNF-α, IL-10 were determined by Luminex® xMAP technology; intestinal permeability was assessed by measuring endotoxins in serum; gastrointestinal symptoms by Gastrointestinal Symptom Rating Scale (GSRS) and dietary intake by food record of three alternate days. Results: Of 43 individuals randomized, 26 completed the follow-up [age= 55±12; 53.8% men; 34.6% with diabetes; 84.6% with residual diuresis; dialysis vintage= 16 (5-31) months]. UBF did not promote changes in serum levels of IS (p=0.70), pCS (p=0.70) e IAA (p=0.74). Reduction in serum total IS was observed in a subgroup of participants who had a daily UBF intake closer to that proposed in the study [n=11; placebo: median 79.5 μmol/L (31-142) versus UBF: 62.5 μmol/L (31-133), p= 0.009]. This finding was independent of habitual dietary intake and urinary excretion and dialysis removal of IS. No changes were observed in the other analyzed parameters. Conclusion: UBF did not affect either the serum levels of IS or pCS and IAA, a decrease in IS was only found in the subgroup of participants who had a daily UBF intake closer to that proposed in the study.
Introduction: Gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS) and indole 3-acetic acid (IAA), are part of the mammalian serum metabolome. In chronic kidney disease (CKD), the accumulation of these metabolites has been associated to inflammation, cardiovascular disease and mortality from all causes. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating gut microbiota and production of their metabolites. Objectives: To evaluate the effect of unripe banana flour (UBF- 48% of resistant starch, a prebiotic) on serum concentrations of IS, pCS and IAA and on serum inflammatory biomarkers (IL-6, TNF-α, IL-10 e CRP), intestinal permeability and gastrointestinal symptoms in individuals undergoing peritoneal dialysis (PD). Methods: A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch- 12 g/day) for 4 weeks, or vice versa. Between both interventions there was a 4-week washout. Serun concentration of IS, pCS and IAA was determined by high performance liquid chromatography (HPLC); serum levels of IL-6, TNF-α, IL-10 were determined by Luminex® xMAP technology; intestinal permeability was assessed by measuring endotoxins in serum; gastrointestinal symptoms by Gastrointestinal Symptom Rating Scale (GSRS) and dietary intake by food record of three alternate days. Results: Of 43 individuals randomized, 26 completed the follow-up [age= 55±12; 53.8% men; 34.6% with diabetes; 84.6% with residual diuresis; dialysis vintage= 16 (5-31) months]. UBF did not promote changes in serum levels of IS (p=0.70), pCS (p=0.70) e IAA (p=0.74). Reduction in serum total IS was observed in a subgroup of participants who had a daily UBF intake closer to that proposed in the study [n=11; placebo: median 79.5 μmol/L (31-142) versus UBF: 62.5 μmol/L (31-133), p= 0.009]. This finding was independent of habitual dietary intake and urinary excretion and dialysis removal of IS. No changes were observed in the other analyzed parameters. Conclusion: UBF did not affect either the serum levels of IS or pCS and IAA, a decrease in IS was only found in the subgroup of participants who had a daily UBF intake closer to that proposed in the study.