Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women.

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.

Red Meat Intake, Indole-3-Acetate, and Dorea longicatena Together Affect Insulin Resistance after Gastric Bypass.

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.

Gastrointestinal genetic reprogramming of vitamin A metabolic pathways in response of Roux-en-Y gastric bypass.

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.

Genetic reprogramming of remnant duodenum may contribute to type 2 diabetes improvement after Roux-en-Y gastric bypass.

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.

Nutritional guidance, monitoring, and supplementation before and after bariatric surgery - Are we doing this correctly? / Orientación, seguimiento y suplementación nutricional antes y después de la cirugía bariátrica: ¿lo estamos haciendo correctamente?

Background and aims: minimizing nutritional depletions after a Roux-en-Y gastric bypass (RYGB) may improve clinical results in the treatment of obesity. We evaluated nutritional aspects of obese women undergoing RYGB at a reference university hospital with a department specialized in bariatric surgery. Method: based on the Dietary Reference Intakes developed by the Food and Nutrition Council, Institute of Medicine, and the guidelines issued by the American Society for Metabolic and Bariatric Surgery, we assessed the quantitative and qualitative adequacy of nutritional intake, supplementation, and biochemical monitoring of 20 women both before and 3 and 12 months after a RYGB. Data on nutritional intake was obtained by applying different food surveys, quantitatively interpreted by the Virtual Nutri Plus® software and using reference nutritional databases. Results: nutritional intake deficits were already found before the RYGB (p ≤ 0.05). These worsened postoperatively (p ≤ 0.05), a period also marked by a qualitatively poor diet. The nutritional supplementation prescribed did not fully achieve the reference recommendations, and was poorly complied with by patients. Furthermore, nutritional monitoring was not carried out in all patients, recommended biochemical markers were not screened, and vitamin D depletions occurred. (AU)

Antecedentes y objetivos: minimizar el deterioro nutricional después del baipás gástrico en Y de Roux (BGYR) puede mejorar los resultados clínicos en el tratamiento de la obesidad. Se evaluaron aspectos nutricionales de mujeres obesas sometidas a BGYR en un hospital universitario de referencia con servicio especializado de cirugía bariátrica. Método: con base en la Ingesta Dietética de Referencia desarrollada por el Consejo de Alimentos y Nutrición del Instituto de Medicina, y las directrices de la Sociedad Estadounidense de Cirugía Bariátrica y Metabólica, evaluamos la adecuación cuantitativa y cualitativa de la ingesta nutricional, la suplementación y el seguimiento bioquímico de 20 mujeres tanto antes como 3 y 12 meses después de un BGYR. Los datos de la ingesta nutricional se obtuvieron mediante la aplicación de diferentes encuestas alimentarias, interpretadas cuantitativamente por el software Virtual Nutri Plus® y utilizando bases de datos nutricionales de referencia. Resultados: se encontraron déficits de ingesta nutricional antes del BGYR (p < 0,05). Estos empeoraron en el postoperatorio (p < 0,05), período también marcado por una mala alimentación cualitativa. La suplementación nutricional prescrita no cumplió plenamente con las recomendaciones de referencia y no fue bien cumplida por los pacientes. Además, la monitorización nutricional no se aplicó en todos los pacientes y no se examinaron todos los marcadores bioquímicos recomendados, hallándose depleciones de vitamina D. (AU)

Nutritional guidance, monitoring, and supplementation before and after bariatric surgery - Are we doing this correctly?

INTRODUCTION: Background and aims: minimizing nutritional depletions after a Roux-en-Y gastric bypass (RYGB) may improve clinical results in the treatment of obesity. We evaluated nutritional aspects of obese women undergoing RYGB at a reference university hospital with a department specialized in bariatric surgery. Method: based on the Dietary Reference Intakes developed by the Food and Nutrition Council, Institute of Medicine, and the guidelines issued by the American Society for Metabolic and Bariatric Surgery, we assessed the quantitative and qualitative adequacy of nutritional intake, supplementation, and biochemical monitoring of 20 women both before and 3 and 12 months after a RYGB. Data on nutritional intake was obtained by applying different food surveys, quantitatively interpreted by the Virtual Nutri Plus® software and using reference nutritional databases. Results: nutritional intake deficits were already found before the RYGB (p ≤ 0.05). These worsened postoperatively (p ≤ 0.05), a period also marked by a qualitatively poor diet. The nutritional supplementation prescribed did not fully achieve the reference recommendations, and was poorly complied with by patients. Furthermore, nutritional monitoring was not carried out in all patients, recommended biochemical markers were not screened, and vitamin D depletions occurred. Conclusion: our data suggest that institutions specialized in bariatric patient care may not be adequately adhering to well known guidelines, or applying efficient strategies to improve compliance.

INTRODUCCIÓN: Antecedentes y objetivos: minimizar el deterioro nutricional después del baipás gástrico en Y de Roux (BGYR) puede mejorar los resultados clínicos en el tratamiento de la obesidad. Se evaluaron aspectos nutricionales de mujeres obesas sometidas a BGYR en un hospital universitario de referencia con servicio especializado de cirugía bariátrica. Método: con base en la Ingesta Dietética de Referencia desarrollada por el Consejo de Alimentos y Nutrición del Instituto de Medicina, y las directrices de la Sociedad Estadounidense de Cirugía Bariátrica y Metabólica, evaluamos la adecuación cuantitativa y cualitativa de la ingesta nutricional, la suplementación y el seguimiento bioquímico de 20 mujeres tanto antes como 3 y 12 meses después de un BGYR. Los datos de la ingesta nutricional se obtuvieron mediante la aplicación de diferentes encuestas alimentarias, interpretadas cuantitativamente por el software Virtual Nutri Plus® y utilizando bases de datos nutricionales de referencia. Resultados: se encontraron déficits de ingesta nutricional antes del BGYR (p < 0,05). Estos empeoraron en el postoperatorio (p < 0,05), período también marcado por una mala alimentación cualitativa. La suplementación nutricional prescrita no cumplió plenamente con las recomendaciones de referencia y no fue bien cumplida por los pacientes. Además, la monitorización nutricional no se aplicó en todos los pacientes y no se examinaron todos los marcadores bioquímicos recomendados, hallándose depleciones de vitamina D. Conclusión: nuestros datos sugieren que las instituciones especializadas en la atención de pacientes bariátricos podrían no estar siguiendo adecuadamente las pautas recomendadas, ni aplicando estrategias eficientes para mejorar su cumplimiento.

Type 2 Diabetes Metabolic Improvement After Roux-en-Y Gastric Bypass May Include a Compensatory Mechanism That Balances Fatty Acid ß and ω Oxidation.

BACKGROUND: More than half of patients who undergo Roux-en-Y gastric bypass (RYGB) can experience type 2 diabetes (T2D) remission, but the systemic and gastrointestinal (GI) metabolic mechanisms of this improvement are still elusive. METHODS: Paired samples collected before and 3 months after RYGB from 28 women with obesity and T2D were analyzed by metabolomics with gas chromatography coupled to mass spectrometry. Samples include plasma (n = 56) and biopsies of gastric pouch (n = 18), gastric remnant (n = 10), duodenum (n = 16), jejunum (n = 18), and ileum (n = 18), collected by double-balloon enteroscopy. RESULTS: After RYGB, improvements in body composition and weight-related and glucose homeostasis parameters were observed. Plasma-enriched metabolic pathways included arginine and proline metabolism, urea and tricarboxylic acid (TCA) cycles, gluconeogenesis, malate-aspartate shuttle, and carnitine synthesis. In GI tissue, we observed alterations of ammonia recycling and carnitine synthesis in gastric pouch, phenylacetate metabolism and trehalose degradation in duodenum and jejunum, ketone bodies in jejunum, and lactose degradation in ileum. Intermediates molecules of the TCA cycle were enriched, particularly in plasma, jejunum, and ileum. Fluctuations of dicarboxylic acids (DCAs) were relevant in several metabolomic tests, and metabolite alterations included aminomalonate and fumaric, malic, oxalic, and succinic acids. The product/substrate relationship between these molecules and its pathways may reflect a compensatory mechanism to balance metabolism. CONCLUSIONS: RYGB was associated with systemic and GI metabolic reprogramming. DCA alterations link ω and ß fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement.

Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission.

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.

Gut Microbiota Profile of Obese Diabetic Women Submitted to Roux-en-Y Gastric Bypass and Its Association with Food Intake and Postoperative Diabetes Remission.

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.

Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study.

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.