RAQUEL SUSANA MATOS DE MIRANDA TORRINHAS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
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- Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study(2019) RAVACCI, Graziela Rosa; ISHIDA, Robson; TORRINHAS, Raquel Suzana; SALA, Priscila; MACHADO, Natasha Mendonca; FONSECA, Danielle Cristina; CANUTO, Gisele Andre Baptista; PINTO, Ernani; NASCIMENTO, Viviane; TAVARES, Marina Franco Maggi; SAKAI, Paulo; FAINTUCH, Joel; SANTO, Marco Aurelio; MOURA, Eduardo Guimaraes Hourneaux; ARTIGIANI NETO, Ricardo; LOGULLO, Angela Flavia; WAITZBERG, Dan LinetzkyWe evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (>= 4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.
- Cell activation state influences the modulation of HLA-DR surface expression on human monocytes/macrophages by parenteral fish oil lipid emulsion(2011) TORRINHAS, R. S.; JACINTHO, T.; GOTO, H.; GIDLUND, M.; SALES, M. M.; OLIVEIRA, P. A.; WAITZBERG, D. L.Abnormal surface expression of HLA-DR by leukocytes is associated with a poor prognosis in critical care patients. Critical care patients often receive total parenteral nutrition with lipid emulsion (LE). In this study we evaluated the influence of fish oil LE (FO) on human monocyte/macrophage (M phi) expression of surface HLA-DR under distinct activation states. Mononuclear leukocytes from the peripheral blood of healthy volunteers (n=18) were cultured for 24 hours without LE (control) or with 3 different concentrations (0.1, 0.25, and 0.5%) of the follow LE: a) pure FO b) FO in association (1:1-v/v) with LE composed of 50% medium-chain trygliceride and 50% soybean oil (MCTSO), and c) pure MCTSO. The leukocytes were also submitted to different cell activation states, as determinate by INF-g addition time: no INF-gamma addition, 18 hours before, or at the time of LE addition. HLA-DR expression on MO surface was evaluated by flow cytometry using specific monoclonal antibodies. In relation to controls (for 0.1%, 0.25%, and 05%: 100) FO decreased the expression of HLA-DR when added alone in simultaneously-activated M., for 0.1%: 70 (59 +/- 73); for 0.25%: 51 (48 +/- 56); and for 05%: 52.5 (50 +/- 58)1 or in association with MCTSO [in simultaneously-activated MO, for 0.1%: 50.5 (47 +/- 61); for 25%: 49 (45 +/- 52); and for 0.5%: 51 (44 54) and in previously-activated Mf, for 1.0%: 63 (44 +/- 88); for 0.25%: 70 (41 +/- 88); and for 0.5%: 59.5 (39 +/- 79)1 in culture medium (Friedman p < 0.05). In relation to controls (for 0.1%, 0.25%, and 0.5%: 100), FO did not influence the expression of these molecules on non-activated M phi [for 0.1%: 87.5(75 +/- 93); for 0.25%: 111 (98 +/- 118); and for 0.5%: 101.5 (84 +/- 113)]. Results show that parenteral FO modulates the expression of HLA-DR on human MO surface accordingly to leukocyte activation state. Further clinical studies evaluating the ideal moment of fish oil LE infusion to modulate leukocyte functions may contribute to a better understanding of its immune modulatory properties.
- Understanding the gut microbiota in cancer cachexia(2023) ROCHA, Ilanna Marques; FONSECA, Danielle Cristina; TORRINHAS, Raquel Susana Matos; WAITZBERG, Dan LinetzkyPurpose of reviewCachexia is a complex, multifactorial syndrome primarily characterized by weight loss, muscle wasting, anorexia, and systemic inflammation. It is prevalent in cancer patients and is associated with a poor prognosis, including lower resistance to intervention toxicity, quality of life, and survival, compared to patients without the syndrome. The gut microbiota and its metabolites have been shown to influence host metabolism and immune response. Our article reviews the current evidence suggesting a role of gut microbiota in the development and progression of cachexia, while discussing the potential mechanisms involved. We also describe promising interventions targeting gut microbiota aiming to improve outcomes related to cachexia.Recent findingsDysbiosis, an imbalance in gut microbiota, has been associated with cancer cachexia through pathways involving muscle wasting, inflammation, and gut barrier dysfunction. Interventions targeting gut microbiota, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have shown promising results in managing this syndrome in animal models. However, evidence in humans is currently limited.Mechanisms linking gut microbiota and cancer cachexia need to be further explored, and additional human research is necessary to evaluate the appropriate dosages, safety, and long-term outcomes of prebiotic and probiotic use in microbiota management for cancer cachexia.
- Human Leukocyte Death After a Preoperative Infusion of Medium/Long-Chain Triglyceride and Fish Oil Parenteral Emulsions: A Randomized Study in Gastrointestinal Cancer Patients(2012) CURY-BOAVENTURA, Maria Fernanda; TORRINHAS, Raquel Susana Matos de Miranda; GODOY, Andre Borella Pereira de; CURI, Rui; WAITZBERG, Dan LinetzkyBackground: Parenteral lipid emulsions (LEs) can influence leukocyte functions. The authors investigated the effect of 2 LEs on leukocyte death in surgical patients with gastrointestinal cancer. Material and Methods: Twenty-five patients from a randomized, double-blind clinical trial (ID: NCT01218841) were randomly included to evaluate leukocyte death after 3 days of preoperative infusion (0.2 g fat/kg/d) of an LE composed equally of medium/long-chain triglycerides and soybean oil (MCTs/LCTs) or pure fish oil (FO). Blood samples were collected before (t0) and after LE infusion (t1) and on the third postoperative day (t2). Results: After LE infusion (t1 vs t0), MCTs/LCTs did not influence cell death; FO slightly increased the proportion of necrotic lymphocytes (5%). At the postoperative period (t2 vs t0), MCTs/LCTs tripled the proportion of apoptotic lymphocytes; FO maintained the slightly increased proportion of necrotic lymphocytes (7%) and reduced the percentage of apoptotic lymphocytes by 74%. In the postoperative period, MCT/LCT emulsion increased the proportion of apoptotic neutrophils, and FO emulsion did not change any parameter of apoptosis in the neutrophil population. There were no differences in lymphocyte or neutrophil death when MCT/LCT and FO treatments were compared during either preoperative or postoperative periods. MCT/LCTs altered the expression of 12 of 108 genes related to cell death, with both pro- and antiapoptotic effects; FO modulated the expression of 7 genes, demonstrating an antiapoptotic effect. Conclusion: In patients with gastrointestinal cancer, preoperative MCT/LCT infusion was associated with postoperative lymphocyte and neutrophil apoptosis. FO has a protective effect on postoperative lymphocyte apoptosis. (JPEN J Parenter Enteral Nutr. 2012; 36: 677-684)
- Pro-Inflammatory Diet Is Correlated with High Veillonella rogosae, Gut Inflammation and Clinical Relapse of Inflammatory Bowel Disease(2023) ROCHA, Ilanna Marques Gomes da; TORRINHAS, Raquel; FONSECA, Danielle; LYRA, Clelia de Oliveira; NERI, Julianna Lys de Sousa Alves; BALMANT, Bianca Depieri; CALLADO, Leticia; CHARLTON, Karen; QUEIROZ, Natalia; WAITZBERG, Dan L.Inflammatory bowel diseases (IBD) are chronic conditions arising from an intricate interplay of genetics and environmental factors, and are associated with gut dysbiosis, inflammation, and gut permeability. In this study, we investigated whether the inflammatory potential of the diet is associated with the gut microbiota profile, inflammation, and permeability in forty patients with IBD in clinical remission. The dietary inflammatory index (DII) score was used to assess the inflammatory potential of the diet. The fecal microbiota profile was analyzed using 16SrRNA (V3-V4) gene sequencing, while fecal zonulin and calprotectin levels were measured with enzyme-linked immunosorbent assays. We found a positive correlation between the DII score and elevated calprotectin levels (Rho = 0.498; p = 0.001), but not with zonulin levels. Although alpha- and beta-diversity did not significantly differ across DII quartiles, the most pro-inflammatory diet group exhibited a higher fecal abundance of Veillonella rogosae (p = 0.026). In addition, the abundance of some specific bacteria sequences showed an exponential behavior across DII quartiles and a correlation with calprotectin or zonulin levels (p <= 0.050). This included a positive correlation between sq702. Veillonella rogosae and fecal calprotectin levels (Rho = 0.419, p = 0.007). DII, calprotectin, and zonulin levels were identified as significant predictors of 6-month disease relapse (p <= 0.050). Our findings suggest a potential relationship of a pro-inflammatory diet intake with Veillonella rogosae and calprotectin levels in IBD patients in clinical remission, which may contribute to disease relapse.
- Parenteral fi sh oil: An adjuvant pharmacotherapy for coronavirus disease 2019?(2021) TORRINHAS, Raquel S.; CALDER, Philip C.; LEMOS, Gabriela O.; WAITZBERG, Dan L.The new coronavirus associated with severe acute respiratory syndrome (SARS-CoV-2), surprisingly, does not affect only the lungs. The severe response to SARS-CoV-2 appears to include a ""cytokine storm,"" which indicates a state of hyperinflammation and subsequent dysfunction of multiple organs and tissues in the most severe cases. This could be the reason why populations at the highest risk for death from the SARS-CoV-2 infection-induced disease (coronavirus disease 2019 [COVID-19]) are those suffering from chronic lowgrade inflammation, but prone to hyperinflammation. This includes individuals of advanced age and those with obesity, type 2 diabetes, hypertension, and metabolic syndrome. Inflammation resolution is strongly dependent on lipid mediators, the specialized pro-resolution mediators (SPMs). oi-3 polyunsaturated fatty acids (oi-3 PUFAs) are precursors of very potent SPMs, including resolvins, protectins, and maresins. Additionally, they are associated with a less aggressive inflammatory initiation, after competing with oi-6 fatty acids for eicosanoid synthesis. Therefore, it makes sense to consider the use of oi-3 PUFAs for clinical management of COVID-19 patients. oi-3 PUFAs may be given by oral, enteral, or parenteral routes; however, the parenteral route favors faster incorporation into plasma phospholipids, blood cells, and tissues. Here, we discuss these aspects to propose the parenteral infusion of oi-3 PUFAs as adjuvant immunopharmacotherapy for hospitalized patients with COVID-19.
- Response to Bistrian BR. Parenteral Fish-Oil Emulsions in Critically Ill COVID-19 Emulsions(2020) TORRINHAS, Raquel S.; CALDER, Philip C.; WAITZBERG, Dan L.In this letter we discuss the proposition of Bristian BR (2020) to use the intravenous administration of fish-oil emulsions in critically ill patients with Coronavirus Disease 2019 (COVID-19). We consider that immune-modulatory properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, rapidly provided in high amounts by fish-oil emulsions, may be important to change the course of COVID-19's death pathway. Prescriptions should be based on body weight (eg, 0.2-g pure fish-oil lipid emulsion/kg body weight/d) and also should consider combining the parenteral administration of fish-oil emulsions with low oral aspirin intake to trigger resolvin synthesis from EPA and DHA.
- Megamonas funiformis, Plasma Zonulin, and Sodium Intake Affect C3 Complement Levels in Inactive Systemic Lupus Erythematosus(2023) BALMANT, Bianca Depieri; FONSECA, Danielle Cristina; PRUDENCIO, Ana Paula Aguiar; ROCHA, Ilanna Marques; CALLADO, Leticia; ALVES, Juliana Tepedino Martins; TORRINHAS, Raquel Susana Matos de Miranda; BORBA, Eduardo Ferreira; WAITZBERG, Dan LinetzkyThe etiology of systemic lupus erythematosus (SLE) remains unclear, with both genetic and environmental factors potentially contributing. This study aimed to explore the relationship among gut microbiota (GM), intestinal permeability, and food intake with inflammatory markers in inactive SLE patients. A total of 22 women with inactive SLE and 20 healthy volunteers were enrolled, and dietary intake was assessed through 24-h dietary recalls. Plasma zonulin was used to evaluate intestinal permeability, while GM was determined by 16S rRNA sequencing. Regression models were used to analyze laboratory markers of lupus disease (C3 and C4 complement and C-reactive protein). Our results showed that the genus Megamonas was significantly enriched in the iSLE group (p < 0.001), with Megamonas funiformis associated with all evaluated laboratory tests (p < 0.05). Plasma zonulin was associated with C3 levels (p = 0.016), and sodium intake was negatively associated with C3 and C4 levels (p < 0.05). A combined model incorporating variables from each group (GM, intestinal permeability, and food intake) demonstrated a significant association with C3 complement levels (p < 0.01). These findings suggest that increased Megamonas funiformis abundance, elevated plasma zonulin, and higher sodium intake may contribute to reduced C3 complement levels in women with inactive SLE.
- Reduced intestinal FADS1 gene expression and plasma omega-3 fatty acids following Roux-en-Y gastric bypass(2019) GARLA, Priscila; SALA, Priscila; TORRINHAS, Raquel Susana Matos; MACHADO, Natasha Mendonca; FONSECA, Danielle Cristina; SILVA, Mariane Marques da; RAVACCI, Graziela Rosa; BELARMINO, Giliane; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimardes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; SILVA, Ismael Dale Cotrim Guerreiro da; PEREIRA, Claudia Cristina Alves; HEYMSFIELD, Steven; CORREA-GIANNELLA, Maria Lucia Cardillo; CALDER, Philip C.; WAITZBERG, Dan LinetzkyBackground & aims: Roux-en-Y gastric bypass (RYGB) limits food ingestion and may alter the intestinal expression of genes involved in the endogenous synthesis of polyunsaturated fatty acids (PUFAs). These changes may decrease the systemic availability of bioactive PUFA5 after RYGB. To study the impact of RYGB on the dietary ingestion and plasma concentration of PUFA5 and on the intestinal expression of genes involved in their endogenous biosynthesis in severely obese women with type 2 diabetes. Methods: Before, and 3 and 12 months after RYGB, obese women (n = 20) self-reported a seven-day dietary record, answered a food frequency query and provided plasma samples for alpha-linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acid assessment by gas chromatography. Intestinal biopsies (duodenum, jejunum and ileum) were collected through double balloon endoscopy before and 3 months after RYGB for gene expression analysis by microarray (Human GeneChip 1.0 ST array) and RT-qPCR validation. Results: Compared to the preoperative period, patients had decreased intakes of PUFAs, fish and soybean oil (p < 0.05) and lower plasma concentrations of ALA and EPA (p < 0.001) 3 and 12 months after RYGB. FADS] gene expression was lower in duodenum (RT-qPCR fold change = 1.620, p < 0.05) and jejunum (RT-qPCR fold change = -1.549, p < 0.05) 3 months following RYGB, compared to before surgery. Conclusion: RYGB decreased PUFA ingestion, plasma ALA and EPA levels, and intestinal expression of FADS] gene. The latter encodes a key enzyme involved in endogenous biosynthesis of PUFA5. These data suggest that supplementation of omega-3 PUFAs may be required for obese patients undergoing RYGB. Clinical Trial Registry number and website: www.clinicaltrials.gov NCT01251016; Plataforma Brasil - 19339913.0.0000.0068. (C) 02018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
- Effect of Roux-en-Y Gastric Bypass on circulating oxylipin profile in women with obesity and type 2 diabetes(2024) MANCUZO, Daiane Cavalari; MACHADO, Natasha Mendonca; TEPPEDINO, Juliana; SANTANDER, Lucas; CALDER, Philip C.; WAITZBERG, Dan Linetzky; TORRINHAS, Raquel SusanaBackground & Aims: Chronic inflammation associated with obesity directly contributes to metabolic comor-bidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for obesity-associated T2D. We investigated the effect of RYGB on the circulating profile of oxylipins derived from arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids as a potential mechanism un-derlying the metabolic benefits of the surgery. Methods: Plasma samples were collected from 28 women with obesity and T2D before and 3 months after RYGB. Circulating levels of oxylipins and their precursors, along with biochemical markers of glucose homeostasis, were evaluated using untargeted mass spectrometry and routine biochemical techniques, respectively. Results: No significant changes were observed in the levels of oxylipins derived from EPA and DHA. However, there was an increase in ARA and its derived oxylipins, TXB2 (an inert derivative of TXA2) and PGD2 (Wilcoxon, p <= 0.05). Positive correlations were observed between hemoglobin A1c levels and TXB2 as well as ARA levels (Spearman, p <= 0.05). Conclusions: Our data suggest that the anti-inflammatory oxylipins derived from EPA and DHA may not be involved in the metabolic benefits associated with RYGB. However, the findings indicate that the pro-inflammatory oxylipin TXA2 and its precursor ARA may negatively impact glucose homeostasis both before and after RYGB.