RESUMEN
Imbalanced dietary intake is associated with the development of inflammatory bowel diseases (IBDs) and is often observed during the active phases of Crohn's disease (CD) and ulcerative colitis (UC). Cumulative data also suggest the potential for dietary manipulation in avoiding IBD relapse. However, there is a paucity of dietary data from patients in clinical remission to guide such an approach. Our study aimed to characterize the dietary pattern and adequacy of patients with IBD in clinical remission. Data on dietary intake (three alternate 24 h food records) were collected from 40 patients with IBD (20 CD and 20 UC) and 45 gender-matched healthy controls (HC). Statistical comparisons between patients and controls employed Student's t-test, Mann-Whitney U, chi-squared, and Fisher's exact tests. The adequacy of dietary intake of IBD patients was further studied by assessing the nutrient inadequacy prevalence, estimated using the Dietary Reference Intakes (DRI) framework and the Estimated Average Requirement (EAR) parameter. We observed significant dietary imbalances among patients with IBD compared to the HC group, marked by disparities in both macronutrient and micronutrient intakes. Inadequacies with frequencies >80% were observed for the ingestion of total fiber and 13 micronutrients in IBD patients. Our preliminary findings suggest that imbalanced dietary intake is also characteristic among individuals with IBD during clinical remission, corroborating the need for dietary interventions in this population.
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Colitis Ulcerosa , Enfermedad de Crohn , Dieta , Enfermedades Inflamatorias del Intestino , Inducción de Remisión , Humanos , Femenino , Masculino , Adulto , Colitis Ulcerosa/dietoterapia , Enfermedad de Crohn/dietoterapia , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/dietoterapia , Micronutrientes/administración & dosificación , Estudios de Casos y Controles , Adulto Joven , Fibras de la Dieta/administración & dosificación , Estado Nutricional , Registros de DietaRESUMEN
Gut microbiota has been implicated in various clinical conditions, yet the substantial heterogeneity in gut microbiota research results necessitates a more sophisticated approach than merely identifying statistically different microbial taxa between healthy and unhealthy individuals. Our study seeks to not only select microbial taxa but also explore their synergy with phenotypic host variables to develop novel predictive models for specific clinical conditions. DESIGN: We assessed 50 healthy and 152 unhealthy individuals for phenotypic variables (PV) and gut microbiota (GM) composition by 16S rRNA gene sequencing. The entire modeling process was conducted in the R environment using the Random Forest algorithm. Model performance was assessed through ROC curve construction. RESULTS: We evaluated 52 bacterial taxa and pre-selected PV (p < 0.05) for their contribution to the final models. Across all diseases, the models achieved their best performance when GM and PV data were integrated. Notably, the integrated predictive models demonstrated exceptional performance for rheumatoid arthritis (AUC = 88.03%), type 2 diabetes (AUC = 96.96%), systemic lupus erythematosus (AUC = 98.4%), and type 1 diabetes (AUC = 86.19%). CONCLUSION: Our findings underscore that the selection of bacterial taxa based solely on differences in relative abundance between groups is insufficient to serve as clinical markers. Machine learning techniques are essential for mitigating the considerable variability observed within gut microbiota. In our study, the use of microbial taxa alone exhibited limited predictive power for health outcomes, while the integration of phenotypic variables into predictive models substantially enhanced their predictive capabilities.
What is Already Known on this Subject? While the gut microbiota has been implicated as potential signatures or biomarkers for various clinical conditions, the establishment of causality in humans remains largely elusive.The role of the gut microbiota in maintaining the host organism's proper physiological function is well-established, yet data regarding the composition of the gut microbiota in disease states often suffer from poor reproducibility.What Are the New Findings? Our study demonstrates that relying solely on differences in the relative abundance of bacterial taxa between groups falls short as a means of identifying clinical markers.We advocate the use of robust statistical tools, such as bootstrapping, to mitigate the substantial variability observed in gut microbiota studies, thereby enhancing the reproducibility of research findings.Our findings underscore the limited predictive power of microbial taxa in isolation for health outcomes.The integration of phenotypic variables into predictive models with gut microbiota significantly augments the ability to predict health outcomes.How This Study Might Advance Research Despite the growing enthusiasm for using gut microbiota as biomarkers for various clinical conditions, the lack of standardization throughout the research process impedes progress in this field.Our study emphasizes the necessity of rigorously testing predictions of clinical conditions based on gut microbiota using bootstrapping techniques, promoting greater reproducibility in research findings.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , BiomarcadoresRESUMEN
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 α- and ß-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.
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Enfermedades Inflamatorias del Intestino , Humanos , Biomarcadores , Inflamación , Heces/microbiología , Enfermedad Crónica , Dieta , Recurrencia , Complejo de Antígeno L1 de LeucocitoRESUMEN
Practical 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.
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Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Disbiosis/diagnóstico , ARN Ribosómico 16S/genética , Intestinos , Heces , Encuestas y CuestionariosRESUMEN
PURPOSE OF REVIEW: Cachexia 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 FINDINGS: Dysbiosis, 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. SUMMARY: 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.
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Microbioma Gastrointestinal , Neoplasias , Probióticos , Simbióticos , Animales , Humanos , Microbioma Gastrointestinal/fisiología , Caquexia/terapia , Caquexia/complicaciones , Calidad de Vida , Probióticos/uso terapéutico , Neoplasias/complicaciones , Prebióticos , Inflamación/complicaciones , Disbiosis/complicacionesRESUMEN
OBJECTIVES: Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastrointestinal 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 mechanism 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 correlated 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 transcriptomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.
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Receptor 2 de Folato , Derivación Gástrica , Obesidad Mórbida , Humanos , Femenino , Ácido Fólico , Obesidad/genética , Obesidad/cirugía , Obesidad/metabolismo , Intestinos/cirugía , Yeyuno/cirugía , Yeyuno/metabolismo , Obesidad Mórbida/genética , Obesidad Mórbida/cirugía , Receptor 2 de Folato/metabolismoRESUMEN
The 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.
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Lupus Eritematoso Sistémico , Sodio en la Dieta , Humanos , Femenino , Complemento C3/metabolismo , ARN Ribosómico 16SRESUMEN
Roux-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 {R2 0.80, R2 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.
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Diabetes Mellitus Tipo 2 , Derivación Gástrica , Resistencia a la Insulina , Obesidad Mórbida , Carne Roja , Humanos , Femenino , ARN Ribosómico 16S , Triptófano , Acetatos , Indoles , Glucemia/metabolismo , Insulina , Obesidad Mórbida/cirugíaRESUMEN
Roux-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/m2 [mean±SD]) before and three months after RYGB (BMI, 38.2±4.2 kg/m2). 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 retinol 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 retinol 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 µg RE/day) of oral retinol palmitate, serum concentrations were lower in the post-operative when compared to pre-operative period (0.35±0.14 µg/L vs. 0.52±0.33 µg/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.
RESUMEN
OBJECTIVES: Type 2 diabetes control occurs within a few days after Roux-en-Y gastric bypass (RYGB) and might be related to intestinal adaptation to the new anatomic arrangement. The aim of this study was to evaluate the intestinal transcriptome response to RYGB and its correlation with markers of glycemic homeostasis. METHODS: Global transcriptomic analyses performed by microarray technique were conducted in intestinal biopsies collected from adult women with obesity (N = 20) and T2D before and 3 mo after RYGB. Clinical and biochemical markers of glycemic homeostasis were also evaluated. At 1-y postoperative, patients were classified as responsive (R) or non-responsive (NR) to complete T2D remission according to the American Diabetes Association criteria. Intestinal differentially expressed genes (DEGs) were analyzed separately in the two groups, validated by reverse transcription quantitative polymerase chain reaction, and applied in functional enrichment and canonical pathway analysis. Spearman correlations between clinical and biochemical variables with DEGs were conducted. Twelve patients were classified as R and displayed 62 (duodenum), 241 (jejunum), and 63 (ileum) DEGs. RESULTS: Eight of the patients with DEGs presented very strong or strong positive correlations with glycemia or glycated hemoglobin. Duodenal changes of genes involved in the LXR/RXR pathway were more likely to be associated with T2D. CONCLUSION: In obese women, complete remission of T2D after RYGB might include intestinal transcriptomic changes that suggest a potential role of intracellular cholesterol and lipid homeostasis on glucose control.
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Diabetes Mellitus Tipo 2 , Derivación Gástrica , Obesidad Mórbida , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirugía , Duodeno/metabolismo , Duodeno/cirugía , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Obesidad/genética , Obesidad/metabolismo , Obesidad/cirugía , Obesidad Mórbida/complicaciones , Obesidad Mórbida/genética , Obesidad Mórbida/cirugíaRESUMEN
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 hyperinflammation. 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'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 dysbiosis.
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Tratamiento Farmacológico de COVID-19 , Disbiosis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Hidroxicloroquina/efectos adversos , COVID-19/microbiología , Humanos , Hidroxicloroquina/uso terapéuticoRESUMEN
OBJECTIVES: 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.
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Diabetes Mellitus Tipo 2 , Derivación Gástrica , Obesidad Mórbida , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Humanos , Receptores Toll-Like/genética , Pérdida de PesoRESUMEN
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.
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Diabetes Mellitus Tipo 2/microbiología , Ingestión de Alimentos/fisiología , Derivación Gástrica , Microbioma Gastrointestinal/fisiología , Obesidad Mórbida/microbiología , Adulto , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/cirugía , Femenino , Microbioma Gastrointestinal/genética , Humanos , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Periodo Posoperatorio , ARN Ribosómico 16S/análisis , Inducción de Remisión , Resultado del TratamientoRESUMEN
Aims: To investigate the arm and hand function in hemodialysis patients. Methods: Upper limb function using validated questionnaires such as Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), Cochin and Boston were applied to 57 chronic renal failure patients on hemodialysis and 60 healthy controls. Epidemiological data, data on pain and paresthesia in the upper limb and handgrip strength were obtained. Results: The three questionnaires showed worse performance of upper limb function in chronic renal failure patients than controls: DASH questionnaire with P = 0.05; Cochin questionnaire with P = 0.0004 and Boston questionnaire with P = 0.03. The questionnaire scores were affected by presence of pain (P = 0.05 for DASH and < 0.0001 for Boston questionnaires) and paresthesia (DASH with P = 0.003; Cochin with P = 0.01 and Boston questionnaire with P < 0.0001). Handgrip strength was lower in hemodialysis patients when compared with controls (P = 0.02) but did not affect the performance of any of the studied questionnaires. Conclusions: Upper limb function is impaired in hemodialysis patients and the main associations found were with pain and paresthesia.
Objetivos: Investigar a função do braço e da mão em pacientes em hemodiálise. Métodos: A função dos membros superiores foi investigada utilizando-se questionários validados, como Disability of the Arm, Shoulder and Hand Questionnaire (DASH), Cochin e Boston, sendo aplicada a 57 pacientes com insuficiência renal crônica em hemodiálise e 60 controles saudáveis. Foram obtidos dados epidemiológicos tais como dor e parestesia no membro superior e força de preensão manual. Resultados: Os três questionários apresentaram pior desempenho da função do membro superior em pacientes com insuficiência renal crônica do que os controles: questionário DASH com P = 0,05; questionário de Cochin com P = 0,0004 e questionário de Boston com P = 0,03. Os escores do questionário foram afetados pela presença de dor (P = 0,05 para DASH e <0,0001 para questionários de Boston) e parestesia (DASH com P = 0,003; Cochin com P = 0,01 e Boston com P <0,0001). A força de preensão manual foi menor nos pacientes em hemodiálise quando comparados aos controles (P = 0,02), mas não afetou o desempenho de nenhum dos questionários estudados. Conclusões: A função do membro superior é prejudicada em pacientes em hemodiálise e as principais associações encontradas foram com dor e parestesia.
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Diálisis Renal , Dolor , Parestesia , Fístula Arteriovenosa , Insuficiencia Renal Crónica , Enfermedades Renales , Medicina , NefrologíaRESUMEN
We 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.
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Obesidad/patología , Estómago/patología , Adolescente , Adulto , Femenino , Derivación Gástrica/métodos , Jugo Gástrico/fisiología , Expresión Génica/fisiología , Humanos , Inflamación/patología , Inflamación/cirugía , Metabolómica/métodos , Persona de Mediana Edad , Obesidad/cirugía , Estómago/cirugía , Transcriptoma/fisiología , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
BACKGROUND & 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 PUFAs after RYGB. To study the impact of RYGB on the dietary ingestion and plasma concentration of PUFAs 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. FADS1 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 FADS1 gene. The latter encodes a key enzyme involved in endogenous biosynthesis of PUFAs. 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.
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Ácido Graso Desaturasas , Ácidos Grasos Omega-3/sangre , Derivación Gástrica , Adolescente , Adulto , delta-5 Desaturasa de Ácido Graso , Registros de Dieta , Ácido Graso Desaturasas/análisis , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Femenino , Humanos , Intestinos/química , Persona de Mediana Edad , Obesidad/metabolismo , Obesidad/cirugía , Adulto JovenRESUMEN
BACKGROUND: Mechanisms of type 2 diabetes remission (T2Dr) after Roux-en-Y gastric bypass (RYGB) in obese patients appear to involve gastrointestinal hormones. OBJECTIVE: 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. SETTING: 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. RESULTS: 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. CONCLUSIONS: After RYGB, over-expression of GHRL gene occurs only in the excluded stomach with no correlation to T2Dr.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirugía , Derivación Gástrica , Mucosa Gástrica/metabolismo , Ghrelina/genética , Obesidad/genética , Obesidad/cirugía , Adolescente , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/cirugía , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ghrelina/sangre , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad Mórbida/genética , Obesidad Mórbida/metabolismo , Obesidad Mórbida/cirugía , Periodo Posoperatorio , Inducción de Remisión , Estómago/patología , Estómago/cirugía , Regulación hacia Arriba/genética , Adulto JovenRESUMEN
Eating habits, lifestyles, and exposure to specific environmental factors can greatly impact the risk of developing type 2 diabetes (T2D), influence the genome epigenetically, and affect the expression of genes, including genes related to glycemic control, at any stage of life. The epigenetic mechanism underlying obesity and T2D pathogenesis remains poorly understood. Conventional strategies for the treatment of obesity and its comorbidities often have poor long-term adherence, and pharmacological interventions are limited. Bariatric surgery is the most effective current option to treat severe obesity, and Roux-en-Y gastric bypass (RYGB) is the most applied technique worldwide. Epigenetic changes differ depending on the approach used to treat obesity and its associated comorbidities (clinical or surgical). Compared to primary clinical care, bariatric surgery leads to much greater loss of body weight and higher remission rates of T2D and metabolic syndrome, with methylation profiles in promoter regions of genes in obese individuals becoming similar to those of normal-weight individuals. Bariatric surgery can influence DNA methylation in parallel with changes in gene expression pattern. Changes in clinical biomarkers that reflect improvements in glucose and lipid metabolism after RYGB often occur before major weight loss and are coordinated by surgery-induced changes in intestinal hormones. Therefore, the intestine methylation profile would assist in understanding the mechanisms involved in improved glycemic control after bariatric surgery. The main objectives in this area for the future are to identify epigenetic marks that could be used as early indicators of metabolic risk, and to develop treatments able to delay or even reverse these epigenetic changes. Studies that provide the "human epigenetic profile" will be of considerable value to identify tissue-specific epigenetic signatures and their role in the development of chronic diseases. Further studies should apply methods based on global analysis of the genome to identify methylated sites associated with disease and epigenetic marks associated with the remodeling response to bariatric surgery. This review describes the main epigenetic alterations associated with obesity and T2D and the potential role of RYGB in remodeling these changes.
RESUMEN
BACKGROUND: 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 REG1α and REG3γ 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.
Asunto(s)
Diabetes Mellitus Tipo 2/cirugía , Derivación Gástrica/métodos , Yeyuno/metabolismo , Obesidad/cirugía , Proteínas Asociadas a Pancreatitis/genética , Adolescente , Adulto , Biopsia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Humanos , Intestino Delgado/metabolismo , Intestino Delgado/patología , Islotes Pancreáticos/metabolismo , Persona de Mediana Edad , Obesidad/metabolismo , Obesidad/patología , Obesidad Mórbida/metabolismo , Obesidad Mórbida/patología , Obesidad Mórbida/cirugía , Proteínas Asociadas a Pancreatitis/biosíntesis , Proteínas Asociadas a Pancreatitis/fisiología , Inducción de Remisión , Adulto JovenRESUMEN
OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9±6.2 years; body mass index, 46.5±5.3 kg/m2) with adult-onset type 2 diabetes (fasting plasma glucose ≥126 mg/dl; hemoglobin A1c≥6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P≤0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P≤0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.