DANIELLE CRISTINA FONSECA CANDIAN
Projetos de Pesquisa
Unidades Organizacionais
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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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.
- 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.
- Type 2 Diabetes Remission After Roux-en-Y Gastric Bypass: Evidence for Increased Expression of Jejunal Genes Encoding Regenerating Pancreatic Islet-Derived Proteins as a Potential Mechanism(2017) SALA, Priscila; TORRINHAS, Raquel Susana; FONSECA, Danielle Cristina; HEYMSFIELD, Steven; GIANNELLA-NETO, Daniel; WAITZBERG, Dan LinetzkyBackground Intestinal expression of regenerating pancreatic islet-derived protein-encoding genes (REG) would be enhanced after Roux-en-Y gastric bypass (RYGB) and would affect postoperative type 2 diabetes remission (T2Dr). Methods Intestinal biopsy samples were collected from 20 adult obese women with T2D before and 3 months after RYGB. Levels of REG expression and the gene encoding its putative receptor (EXTL3) were assessed by microarray and validated by quantitative RT-PCR. T2Dr was assessed according to ADA criteria 1 year after RYGB. Results After RYGB, only patients with T2Dr had significantly increased REG1 alpha and REG3 gamma expression in the jejunum, as validated by quantitative RT-PCR. Conclusions Our data provide support for the hypothesis that increased jejunal expression of REG genes after RYGB affects T2Dr, possibly by playing an endocrine function.
- Dys-R Questionnaire: A Novel Screening Tool for Dysbiosis Linked to Impaired Gut Microbiota Richness(2023) BALMANT, Bianca Depieri; FONSECA, Danielle Cristina; ROCHA, Ilanna Marques; CALLADO, Leticia; TORRINHAS, Raquel Susana Matos de Miranda; WAITZBERG, Dan LinetzkyPractical and affordable tools to screen intestinal dysbiosis are needed to support clinical decision making. Our study aimed to design a new subjective screening tool for the risk of intestinal dysbiosis from a previously described nonvalidated questionnaire (DYS/FQM) and based on subjective and objective data. A total of 219 individuals comprised the chronic diseases (CD; n = 167) and healthy control (HC; 52 subjects) groups. Sociodemographic, anthropometric, body composition, lifestyle, past history, intestinal health, and dietary data were collected. The gut microbiota (GM) profile was assessed from fecal samples using the 16S rRNA sequencing. Scores for the new tool (Dys-R Questionnaire) were assigned using discrete optimization techniques. The association between Dys-R scores and dysbiosis risk was assessed through correlation, simple linear models, sensitivity, specificity, as well as positive and negative predictive values. We found significant differences in the Chao1 Index between CD and HC groups (adjusted p-value = 0.029), highlighting lower GM richness as the primary marker for intestinal dysbiosis. DYS/FQM showed poor performance in identifying poor GM richness. Dys-R exhibited a 42% sensitivity, 82% specificity, 79% positive predictive value (PPV), and 55% negative predictive value (NPV) to identify poor GM richness. The new Dys-R questionnaire showed good performance in ruling out dysbiosis.
- Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women(2023) FERREIRA, Beatriz de Azevedo Muner; FONSECA, Danielle Cristina; SALA, Priscila; ALVES, Juliana Tepedino Martins; PRUDENCIO, Ana Paula Aguiar; MACHADO, Natasha Mendonca; MARQUES, Mariane; BARCELOS, Samira; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux De; SAKAI, Paulo; SANTE, Marco Aurelio; TORRINHAS, Raquel Susana Matos de Miranda; WAITZBERG, Dan LinetzkyObjectives: Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastroin-testinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mecha-nism contributing to its postoperative deficiency. Methods: Biopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured. Results: Compared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/ receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations corre-lated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001). Conclusion: The present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcrip-tomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.(c) 2023 Elsevier Inc. All rights reserved.
- Red Meat Intake, Indole-3-Acetate, and Dorea longicatena Together Affect Insulin Resistance after Gastric Bypass(2023) PRUDENCIO, Ana Paula Aguiar; FONSECA, Danielle Cristina; MACHADO, Natasha Mendonca; ALVES, Juliana Tepedino Martins; SALA, Priscila; FERNANDES, Gabriel R. R.; TORRINHAS, Raquel Susana; WAITZBERG, Dan LinetzkyRoux-en-Y Gastric bypass (RYGB) promotes improvement in type 2 diabetes (T2D) shortly after surgery, with metabolic mechanisms yet to be elucidated. This study aimed to investigate the relationship between food intake, tryptophan metabolism, and gut microbiota on the glycemic control of obese T2D women after RYGB surgery. Twenty T2D women who underwent RYGB were evaluated before and three months after surgery. Food intake data were obtained by a seven-day food record and a food frequency questionnaire. Tryptophan metabolites were determined by untargeted metabolomic analysis, and the gut microbiota was determined by 16S rRNA sequencing. The glycemic outcomes were fasting blood glucose, HbA1C, HOMA-IR, and HOMA-beta. Linear regression models were applied to assess the associations between the changes in food intake, tryptophan metabolism, and gut microbiota on glycemic control after RYGB. All variables changed after RYGB (p < 0.05), except for tryptophan intake. Jointly, the variation in red meat intake, plasma indole-3-acetate, and Dorea longicatena was associated with postoperative HOMA-IR {R-2 0.80, R-2 adj 0.74; p < 0.01}. Red meat intake decreased three months after bariatric surgery while indole-3-acetate and Dorea longicatena increased in the same period. These combined variables were associated with better insulin resistance in T2D women after RYGB.
- Gut Microbiota Profile of Obese Diabetic Women Submitted to Roux-en-Y Gastric Bypass and Its Association with Food Intake and Postoperative Diabetes Remission(2020) ASSAL, Karina Al; PRIFTI, Edi; BELDA, Eugeni; SALA, Priscila; CLEMENT, Karine; DAO, Maria-Carlota; DORE, Joel; LEVENEZ, Florence; TADDEI, Carla R.; FONSECA, Danielle Cristina; ROCHA, Ilanna Marques; BALMANT, Bianca Depieri; THOMAS, Andrew Maltez; SANTO, Marco A.; DIAS-NETO, Emmanuel; SETUBAL, Joao Carlos; ZUCKER, Jean-Daniel; BELARMINO, Giliane; TORRINHAS, Raquel Susana; WAITZBERG, Dan L.Gut microbiota composition is influenced by environmental factors and has been shown to impact body metabolism. Objective: To assess the gut microbiota profile before and after Roux-en-Y gastric bypass (RYGB) and the correlation with food intake and postoperative type 2 diabetes remission (T2Dr). Design: Gut microbiota profile from obese diabetic women was evaluated before (n = 25) and 3 (n = 20) and 12 months (n = 14) after RYGB, using MiSeq Illumina-based V4 bacterial 16S rRNA gene profiling. Data on food intake (7-day record) and T2Dr (American Diabetes Association (ADA) criteria) were recorded. Results: Preoperatively, the abundance of five bacteria genera differed between patients with (57%) and without T2Dr (p < 0.050). Preoperative gut bacteria genus signature was able to predict the T2Dr status with 0.94 accuracy ROC curve (receiver operating characteristic curve). Postoperatively (vs. preoperative), the relative abundance of some gut bacteria genera changed, the gut microbial richness increased, and the Firmicutes to Bacteroidetes ratio (rFB) decreased (p < 0.05) regardless of T2Dr. Richness levels was correlated with dietary profile pre and postoperatively, mainly displaying positive and inverse correlations with fiber and lipid intakes, respectively (p < 0.05). Conclusions: Gut microbiota profile was influenced by RYGB and correlated with diet and T2Dr preoperatively, suggesting the possibility to assess its composition to predict postoperative T2Dr.
- The SURMetaGIT study: Design and rationale for a prospective pan-omics examination of the gastrointestinal response to Roux-en-Y gastric bypass surgery(2016) SALA, Priscila; BELARMINO, Giliane; MACHADO, Natasha Mendonca; CARDINELLI, Camila Siqueira; ASSAL, Karina Al; SILVA, Mariane Marques; FONSECA, Danielle Cristina; ISHIDA, Robson Kiyoshi; SANTO, Marco Aurelio; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; GUARDA, Ismael Francisco Mota Siqueira; SILVA, Ismael Dale Cotrim Guerreiro da; RODRIGUES, Agatha Sacramento; PEREIRA, Carlos Alberto de Braganca; HEYMSFIELD, Steven; DORE, Joel; TORRINHAS, Raquel Susana Matos de Miranda; GIANNELLA-NETO, Daniel; WAITZBERG, Dan LinetzkyObjective: To describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study's design and challenges faced in its application are detailed. Methods: This observational, longitudinal, prospective study involved collection of gastrointestinal biopsy specimens, faeces, urine, and blood from 25 obese women with T2DM who were candidates for RYGB (20 patients for omics assessment and 5 for omics validation). These collections were performed preoperatively and 3 and 24 months postoperatively. Gastrointestinal transcriptomics; faecal metagenomics and metabolomics; plasma proteomics, lipidomics, and metabolomics; and biochemical, nutritional, and metabolic data were assessed to identify their short- and long-term correlations with T2DM remission. Results: Data were collected from 20 patients before and 3 months after RYGB. These patients have nearly completed the 2-year follow-up assessments. The five additional patients are currently being selected for omics data validation. Conclusion: The multi-integrated pan-omics approach of the SURMetaGIT study enables integrated analysis of data that will contribute to the understanding of molecular mechanisms involved in T2DM remission after RYGB.
- Upregulation of Ghrelin Gene Expression in the Excluded Stomach of Obese Women with Type 2 Diabetes After Roux-en-Y Gastric Bypass in the SURMetaGIT Study(2018) FONSECA, Danielle Cristina; SALA, Priscila; SINGER, Joelle; SINGER, Pierre; TORRINHAS, Raquel Susana; WAITZBERG, Dan LinetzkyMechanisms of type 2 diabetes remission (T2Dr) after Roux-en-Y gastric bypass (RYGB) in obese patients appear to involve gastrointestinal hormones. The objective of this study is to explore changes in ghrelin plasma levels and ghrelin gastrointestinal gene expression (GHRL) after RYGB, and their relationships to T2Dr. In 20 obese women with T2D, before and 3 months after RYGB, we assessed GHRL expression by microarray and quantitative RT-PCR in gastrointestinal biopsy samples and plasma levels of ghrelin. After RYGB, GHRL expression increased in the excluded stomach (p < 0.05) with no change in other gastrointestinal sites. There were no significant changes in ghrelin plasma levels and no correlations with T2Dr. After RYGB, over-expression of GHRL gene occurs only in the excluded stomach with no correlation to T2Dr.
- 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.