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
11 resultados
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- 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.
- 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.
- 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.
- SARS-CoV-2 infection, gut dysbiosis, and heterogeneous clinical results of hydroxychloroquine on COVID-19 therapy & mdash;Is there a link?(2021) BALMANT, Bianca D.; TORRINHAS, Raquel S.; ROCHA, Ilanna M.; FONSECA, Danielle C.; FORMIGA, Francisco F. C.; BONFA, Eloisa S. D. O.; BORBA, Eduardo F.; WAITZBERG, Dan L.Clinical manifestations of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include gastrointestinal signals and symptoms. Individuals with previous clinical conditions that usually enroll gut dysbiosis have been identified as being at high risk to develop more severe infectious phenotypes. Actually, intestinal dysbiosis has been observed in infected patients and potentially linked to systemic hyper-inflammation. These observations suggest that a previous gut dysbiosis may be aggravated by SARS-CoV-2 infection and related to progression of the coronavirus disease 2019 (COVID-19) into more severe stages. While COVID-19 & rsquo;s pathophysiology is not fully understood, it seems relevant to consider the interactions of candidate therapeutic drugs with the host, gut microbiota, and SARS-CoV-2. Here we summarize scientific evidence supporting the potential relevance of these interactions and suggest that unfavorable clinical data on hydroxychloroquine administration in COVID-19 may have been influenced by the dose provided and its impact on gut dysbiosis. The proposition is based on preliminary data on gut microbiota composition from individuals with inactive systemic lupus erythematosus under exclusive continuous hydroxychloroquine treatment, displaying a direct correlation between drug doses and markers typically associated with gut dys-biosis.
- Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission(2020) SALA, Priscila; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle C.; MACHADO, Natasha Mendonca; SINGER, Joelle; SINGER, Pierre; RAVACCI, Graziela Rosa; BELARMINO, Giliane; FERREIRA, Beatriz A. M.; MARQUES, Mariane; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; SUNAGA, Daniele Yumi; HEYMSFIELD, Steven B.; BEZERRA, Daniele Pereira dos Santos; CORREA-GIANNELLA, Maria Lucia; WAITZBERG, Dan LinetzkyObjectives: Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr Methods: Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined. Results: Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss. Conclusions: RYGB-induced weight loss-independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery.
- 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.
- 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.
- Gastrointestinal genetic reprogramming of vitamin A metabolic pathways in response of Roux-en-Y gastric bypass(2024) SAMPAIO, Priscilla; WAITZBERG, Dan Linetzky; MACHADO, Natasha Mendonca; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle C.; FERREIRA, Beatriz A. M.; MARQUES, Mariane; BARCELOS, Samira; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; HEYMSFIELD, Steven B.; CORREA-GIANNELLA, Maria Lucia; PASSADORE, Mariana Doce; SALA, PriscilaRoux-en-Y gastric bypass (RYGB) is one of the most performed bariatric surgical techniques. However, RYGB commonly results, as side effects, in nutritional deficiencies. This study aimed to examine changes in the expression of vitamin A pathway encoding genes in the gastrointestinal tract (GI) and to evaluate the potential mechanisms associated with hypovitaminosis A after RYGB. Intestinal biopsies were obtained through double-balloon endoscopy in 20 women with obesity (age 46.9 +/- 6.2 years; body mass index [BMI] 46.5 +/- 5.3 kg/m(2) [mean +/- SD]) before and three months after RYGB (BMI, 38.2 +/- 4.2 kg/m(2)). Intestinal mucosal gene microarray analyses were performed in samples using a Human GeneChip 1.0 ST array (Affymetrix). Vitamin A intake was assessed from 7-day food records and serum retinot levels were evaluated by electrochemiluminescence immunoassay. Our results showed the following genes with significant downregulation (p <= 0.05): LIPF (-0.60), NPC1L1 (-0.71), BCO1 (-0.45), and RBP4 (-0.13) in duodenum: CD36 (-0.33), and ISX (-0.43) in jejunum and BCO1 (-0.29) in ileum. No significant changes in vitamin A intake were found (784 +/- 694 retinal equivalents [RE] pre-operative vs. 809 +/- 753 RE post-operative [mean +/- SD]). Although patients were routinely supplemented with 3500 international units IU/day (equivalent to 1050 mu gRE/day) of oral retinal palm itate, serum concentrations were lower in the post-operative when compared to pre-operative period (0.35 +/- 0.14 mu g/L vs. 0.52 +/- 0.33 mu g/L respectively - P=0.07), both within the normal range. After RYGB, the simultaneous change in expression of GI genes, may impair carotenoid metabolism in the enterocytes, formation of nascent chylomicrons and transport of retinol, resulting in lower availability of vitamin A.