Resistant Starch Type-2 Supplementation Does Not Decrease Trimethylamine N-Oxide (TMAO) Plasma Level in Hemodialysis Patients.

Dysbiosis is recognized as a new cardiovascular disease (CVD) risk factor in hemodialysis (HD) patients because it is linked to increased generation in the gut of uremic toxins such as trimethylamine N-Oxide (TMAO) from dietary precursors (choline, betaine, or L-carnitine). Nutritional strategies have been proposed to modulate the gut microbiota and reduce the production of these toxins. This study aimed to evaluate the effect of amylose-resistant starch (RS) supplementation on TMAO plasma levels in HD patients.We conducted a randomized, double-blind, placebo-controlled trial (NCT02706808) with patients undergoing HD enrolled in a previous pilot study. The participants were allocated to RS or placebo groups to receive 16 g/d of RS or placebo for 4 weeks. Plasma TMAO, choline, and betaine levels were measured with LC-MS/MS. Fecal microbiome composition was evaluated by 16S ribosomal RNA sequencing, followed by a search for TMA-associated taxa. Anthropometric, routine biochemical parameters, and food intake were evaluated.Twenty-five participants finished the study, 13 in the RS group, and 12 in the placebo group. RS supplementation did not reduce TMAO plasma levels. Moreover, no significant alterations were observed in choline, betaine, anthropometric, biochemical parameters, or food intake in both groups. Likewise, RS was not found to exert any influence on the proportion of potential TMA-producing bacterial taxa in fecal matter.RS supplementation did not influence plasma TMAO, choline, betaine, or fecal taxa potentially linked to TMAO. Thus, RS does not seem to modify the TMA-associated bacterial taxa, precursors of TMAO.Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2021.1967814 .

Resistant starch supplementation effects on plasma indole 3-acetic acid and aryl hydrocarbon receptor mRNA expression in hemodialysis patients: Randomized, double blind and controlled clinical trial / Efeitos da suplementação de amido resistente no ácido indol-3-acético plasmático e na expressão do mRNA do receptor aril-hidrocarboneto em pacientes em hemodiálise: ensaio clínico randomizado, duplo-cego e controlado

ABSTRACT Introduction: Gut microbiota imbalance is linked to high uremic toxins production such as indole-3-acetic acid (IAA) in chronic kidney disease patients. This toxin can activate the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor involved with inflammation. Strategies to restore gut microbiota balance can be associated with reduced production of IAA and its deleterious effects. This study aimed to evaluate prebiotic resistant starch (RS) supplementation effects on IAA plasma levels and AhR mRNA expression in CKD patients on hemodialysis (HD). Methods: This randomized, double-blind and placebo-controlled clinical trial evaluated forty-two stable HD patients allocated in RS (n=22) or placebo (n=20) groups. Patients received, alternately, cookies and sachets containing 16 g/day of RS (Hi-Maize 260®) or manioc flour for four weeks. Fasting pre-dialysis blood samples were collected and IAA plasma levels measured by high performance liquid chromatography. Peripheral blood mononuclear cells were isolated and processed for AhR and nuclear factor kappa B (NF-κB) mRNA expression analyzes by quantitative real-time PCR. Anthropometric and biochemical parameters, as well as food intake were also evaluated. Results: Thirty-one patients completed the study, 15 in the RS group and 16 in the placebo group. Although there was no significant alteration in IAA plasma levels, neither in AhR mRNA expression and NF-κB mRNA expression after RS supplementation, a positive correlation (r=0.48; p=0.03) was observed between IAA plasma levels and AhR expression at baseline. Conclusion: Even though prebiotic RS supplementation did not influence IAA levels or AhR expression, their positive association reinforces a possible interaction between them.

RESUMO Introdução: O desequilíbrio da microbiota intestinal associa-se à alta produção de toxinas urêmicas tais como ácido indol-3-acético (AIA), em renais crônicos. Essa toxina ativa o receptor aril hidrocarboneto (AhR) - fator de transcrição ativado por ligante, na inflamação. Restaurar o equilíbrio da microbiota intestinal associa-se à produção reduzida de AIA e efeitos deletérios. Avaliamos os efeitos da suplementação de amido resistente prebiótico (AR) sobre AIA sérico e expressão de AhR mRNA em renais crônicos em HD. Métodos: Estudo clínico randomizado, duplo-cego, controlado por placebo, com 42 pacientes em HD, nos grupos AR (n = 22) ou placebo (n = 20). Os pacientes receberam, alternadamente, biscoitos e sachês com 16 g/dia de AR ou polvilho - 4 semanas. Coletamos amostras de sangue em jejum pré-diálise e medimos níveis séricos de AIA por cromatografia líquida de alta eficiência. Isolamos e processamos as células mononucleares do sangue periférico para avaliar expressão AhR mRNA e NF-κB por PCR quantitativo em tempo real. Avaliamos parâmetros antropométricos, bioquímicos e ingestão alimentar. Resultados: 31 pacientes, 15 AR e 16 no placebo. Apesar de não apresentarem alteração significativa nos níveis de AIA, nas expressões de AhR ou NF-κB mRNA pós- suplementação com AR, foi verificada uma correlação positiva (r = 0,48; p = 0,03) entre AIA sérico e expressão de AhR na linha basal. Conclusão: Embora a suplementação com o prebiótico de AR não tenha influenciado os níveis de AIA ou a expressão de AhR, sua associação positiva reforça possível interação entre eles.

Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: A pilot randomized, double-blind, controlled study.

BACKGROUND & AIMS: Chronic kidney disease (CKD) patients have numerous complications associated with inflammation, which is a potential driver for cardiovascular disease. Curcumin, a compound of the curcuminoid class produced by the Curcuma longa, has been reported to activate nuclear factor erythroid factor 2-related (Nrf2) and inhibit nuclear factor kappa-B (NF-kB). Our aim was to evaluate the effects of curcumin juice on the expression of inflammatory transcription factors in hemodialysis (HD) patients. METHODS AND RESULTS: This double-blind randomized pilot study included 31 HD patients divided into two groups: curcumin group (receiving 100 mL of orange juice with 12 g of carrot and 2.5 g of turmeric after each dialysis session/week for 3 months) and control group (receiving the same juice without curcumin); 14 patients in each arm completed the study. The mRNA expression of Nrf2, NF-kB, NLRP3 inflammasome and IL-1ß in peripheral blood mononuclear cells (PBMC; using real-time quantitative polymerase chain reaction, qPCR) and routine biochemistries, food intake and anthropometrics were analyzed. After three months of supplementation, the curcumin group showed a significant decrease in NF-kB mRNA expression (AU) [from 1.08 (0.77-1.38) to 0.52 (0.32-0.95),p = 0.02] and in plasma high sensitivity C-reactive protein (hsCRP) levels [from 3.8 (2.5-6.8) to 2.0 (1.1-3.8) mg/L, p = 0.04]. There was no change in the other evaluated markers. CONCLUSION: Three months treatment with curcumin in CKD patients undergoing HD resulted in decreased markers of inflammation, NF-kB mRNA expression and hsCRP, suggesting that oral supplementation of curcumin may have an anti-inflammatory effect in this patient group. TRIAL REGISTRATION: Approved by the Ethics Committee of the Faculty of Medicine/UFF, number: 2.346.933. This study was registered within ClinicalTrials.gov under the number NCT03475017.