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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/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 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 the duodenum; CD36 (-0.33), and ISX (-0.43) in the jejunum and BCO1 (-0.29) in the 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.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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 β fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement., (© 2020 American Society for Parenteral and Enteral Nutrition.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)