Dietary Profile of Patients with Inflammatory Bowel Disease in Clinical Remission-A Preliminary Study.

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.

Evaluation of gut microbiota predictive potential associated with phenotypic characteristics to identify multifactorial diseases.

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.

Dys-R Questionnaire: A Novel Screening Tool for Dysbiosis Linked to Impaired Gut Microbiota Richness.

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.

Pro-Inflammatory Diet Is Correlated with High Veillonella rogosae, Gut Inflammation and Clinical Relapse of Inflammatory Bowel Disease.

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.

High Prevalence of Energy and Nutrients Inadequacy among Brazilian Older Adults.

Poor nutrition increases the risk of diseases and adverse health outcomes in older adults. We evaluated the potential inadequacy of nutrient intake among older adults in Brazil and its association with body anthropometry and composition outcomes. Dietary intake was obtained from 295 community-living older adults (>60 years old), of both genders, using a seven-day food record. Nutrient inadequacy was further identified based on the Dietary Reference Intakes and European Guidelines. Skeletal muscle mass (SM), strength and performance, and the diagnosis of sarcopenia were assessed using reference methods. Nutritional inadequacy was high, with energy, dietary fiber, and six micronutrients exhibiting the greatest inadequacy levels (>80%). Energy intake was correlated with SM strength (p = 0.000) and performance (p = 0.001). Inadequate energy, fiber, and protein intakes influenced BMI, while inadequate intake of vitamin B6 directly affected the diagnosis of sarcopenia (p ≤ 0.005). Further research is required to investigate whether these inadequacies can be associated with other clinical health outcomes.

Understanding the gut microbiota in cancer cachexia.

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.

Megamonas funiformis, Plasma Zonulin, and Sodium Intake Affect C3 Complement Levels in Inactive Systemic Lupus Erythematosus.

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.

Effect of a parenteral fish-oil-containing lipid emulsion on liver lipid perioxidation and antioxidative defenses in Lewis rats.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), naturally abundant in fish oil (FO), are known for their anti-inflammatory and potential antioxidant properties. The aim in this article is to evaluate the effect of the infusion of a parenteral FO-containing lipid emulsion on markers of liver lipid peroxidation and oxidative stress in rats undergoing central venous catheterization (CVC). METHODS: After 5-day acclimatization, adult Lewis rats (n = 42) receiving a 20-g/day AIN-93M oral diet were randomly subdivided into four groups: (1) basal control (BC) (n = 6), without CVC or LE infusion; (2) SHAM (n = 12), with CVC but without LE infusion; (3) soybean oil (SO)/medium-chain triglyceride (MCT) (n = 12), with CVC and receiving LE without FO (4.3 g/kg fat); and (4) SO/MCT/FO (n = 12), with CVC and receiving LE containing 10% FO (4.3 g/kg fat). Animals from the BC group were euthanized immediately after acclimatization. The remaining groups of animals were euthanized after 48 or 72 h of surgical follow-up to assess profiles of liver and plasma fatty acids by gas chromatography, liver gene transcription factor Nrf2, F2-isoprostane lipid peroxidation biomarker, and the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) by enzyme-linked immunosorbent assay. R program (version 3.2.2) was utilized for data analysis. RESULTS: Compared with the other groups, liver EPA and DHA levels were higher in the SO/MCT/FO group, which also showed the highest liver Nrf2, GPx, SOD, and CAT levels and lower liver F2-isoprostane (P < 0.05). CONCLUSION: Experimental delivery of FO via EPA and DHA sources in a parenteral LE was associated with a liver antioxidant effect.

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.

Nutrients, Physical Activity, and Mitochondrial Dysfunction in the Setting of Metabolic Syndrome.

Metabolic syndrome (MetS) is a cluster of metabolic risk factors for diabetes, coronary heart disease, non-alcoholic fatty liver disease, and some tumors. It includes insulin resistance, visceral adiposity, hypertension, and dyslipidemia. MetS is primarily linked to lipotoxicity, with ectopic fat deposition from fat storage exhaustion, more than obesity per se. Excessive intake of long-chain saturated fatty acid and sugar closely relates to lipotoxicity and MetS through several pathways, including toll-like receptor 4 activation, peroxisome proliferator-activated receptor-gamma regulation (PPARγ), sphingolipids remodeling, and protein kinase C activation. These mechanisms prompt mitochondrial dysfunction, which plays a key role in disrupting the metabolism of fatty acids and proteins and in developing insulin resistance. By contrast, the intake of monounsaturated, polyunsaturated, and medium-chain saturated (low-dose) fatty acids, as well as plant-based proteins and whey protein, favors an improvement in sphingolipid composition and metabolic profile. Along with dietary modification, regular exercises including aerobic, resistance, or combined training can target sphingolipid metabolism and improve mitochondrial function and MetS components. This review aimed to summarize the main dietary and biochemical aspects related to the physiopathology of MetS and its implications for mitochondrial machinery while discussing the potential role of diet and exercise in counteracting this complex clustering of metabolic dysfunctions.

Gastrointestinal and sensory manifestations, nutrition management, and energy-protein intake in hospitalized patients with COVID-19.

BACKGROUND: Gastrointestinal and sensory manifestations (GSMs) of coronavirus disease 2019 (COVID-19) may affect food intake, resulting in malnutrition and poor outcomes. We characterized the impact of GSMs and oral nutrition supplementation on energy-protein intake (EPI) and hospital discharge in adult patients with COVID-19. METHODS: Patients from two hospitals were enrolled (n = 357). We recorded the presence and type of GSM at admission, estimated energy requirements (EER) and the EPI based on regular food intake (plate diagram sheets) during hospital stays. Patients not achieving 60% of their EER from food over 2 consecutive days received oral nutrition supplementation (ONS) with a high-energy-protein oral drink. RESULTS: Most patients (63.6%) presented with GSMs at admission. Anorexia was the most common manifestation (44%). Patients with anorexia or more than one GSMs were more likely to not achieve 60% EER on the first day of follow-up and to require the ONS intervention (P ≤ 0.050). Prevalence of at least one GSM was higher in patients who did not achieve hospital discharge than in patients who achieved it (74.2% vs 54.6%, P = 0.038). The patients requiring ONS (26.9%) demonstrated good adherence to the intervention (79.3%), achieved their EER during 95.7% of the supplementation time, and presented with hospital discharge rates similar to patients not requiring ONS (92.2% vs 91.9%, respectively; P = 1.000). CONCLUSIONS: GSM were prevalent in COVID-19 and it impaired EER attendance and patient recovery. ONS was well-tolerated, aided EER attendance, and potentially facilitated hospital discharge.

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.

Is There an Advantage in Enriching Parenteral Lipid Emulsions Containing Fatty Acids From Fish Oil With Medium-Chain Triglycerides? A Study on Body Pool Concentrations of ω-3 Fatty Acids in Lewis Rats.

BACKGROUND: The addition of medium-chain triglycerides (MCTs) into parenteral lipid emulsions rich in fatty acids from fish oil (FOLEs) has been shown to improve their clearance and extrahepatic uptake. We assessed whether this effect could favor the leukocyte uptake of ω-3 polyunsaturated fatty acids (PUFAs) for immunomodulatory purposes METHODS: Following 5-day adaptation in metabolic cages, 42 male Lewis rats fed with AIN-93M chow were killed (baseline control group [BC]) or submitted to central venous catheterization and distributed into (1) surgical control group without parenteral infusion (chow group), (2) test emulsion (MCT/LCT/FO) group with the parenteral infusion of a FOLE containing 40% MCT, and (3) control emulsion group (LCT/FO) with the parenteral infusion of an FOLE without MCT. The 2 FOLEs had similar ω-3 PUFA contents and ω-6/ω-3 PUFA ratios and were infused during 48 and 72 hours. Concentrations of ω-3 and ω-6 PUFAs in plasma, liver, and blood mononuclear and polymorphonuclear leukocytes were assessed by gas chromatography RESULTS: In both FOLE groups, leukocyte concentrations of ω-3 PUFAs peaked after 48 hours' infusion (vs BC). At this time point, plasma concentrations of ω-3 PUFAs were higher in MCT/LCT/FO group than in LCT/FO group and the opposite was found in the liver (P<.05), but no differences in PUFA concentrations were observed between these groups in leukocytes (P>.05) CONCLUSION: The ω-3 PUFAs provided by FOLEs rich in MCT were less incorporated by liver and remained more available for extrahepatic cell delivery, but this did not result in a clear benefit in increasing their incorporation by peripheral leukocytes.

Cholecystectomy - a potential selection bias in studies assessing the metabolic effects of bariatric surgeries.

Bile acids (BAs) are key mediators of the glycemic control after bariatric surgeries. Cholecystectomy modifies the kinetics of BAs, and whether this procedure influences the BAs pool and its metabolic response to bariatric surgeries is not known. We used targeted and untargeted metabolomics to assess whether cholecystectomy influenced plasma and fecal BAs fluctuations and the systemic metabolomic profile after Roux-en-Y gastric bypass (RYGB). Women with obesity and type 2 diabetes were included. Sample collections and clinical evaluations were performed before and 3 months after RYGB. RYGB influenced 9 fecal and 3 plasma BAs in patients with cholecystectomy (p ≤ 0.05). Comparisons between patients with and without cholecystectomy revealed different concentrations of 4 fecal and 5 plasma BAs (p ≤ 0.05). Cholecystectomy impacted the global metabolomics responses to RYGB, and patients who underwent the gallbladder removal also lacked some significant improvements in clinical markers, primarily the lipid profile. By affecting the BAs concentrations, cholecystectomy seems to alter the systemic metabolic response to RYGB. Therefore, cholecystectomy may act as a bias in assessments of the metabolic effects of bariatric surgeries and their relationships with clinical outcomes.

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.

Response to Bistrian BR. Parenteral Fish-Oil Emulsions in Critically Ill COVID-19 Emulsions.

In this letter we discuss the proposition of Bristian BR (2020) to use the intravenous administration of fish-oil emulsions in critically ill patients with Coronavirus Disease 2019 (COVID-19). We consider that immune-modulatory properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, rapidly provided in high amounts by fish-oil emulsions, may be important to change the course of COVID-19's death pathway. Prescriptions should be based on body weight (eg, 0.2-g pure fish-oil lipid emulsion/kg body weight/d) and also should consider combining the parenteral administration of fish-oil emulsions with low oral aspirin intake to trigger resolvin synthesis from EPA and DHA.

Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study.

Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science ® ) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved one-carbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.

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.