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Individuals with type 2 diabetes (T2D) show signs of low-grade inflammation, which is related to the development of insulin resistance and beta-cell dysfunction. However, the underlying triggers remain unknown. The gut microbiota is a plausible source as it comprises pro-inflammatory bacteria, bacterial metabolites and viruses, including (bacterio)phages. These prokaryotic viruses have been shown to mediate inflammatory responses in gastrointestinal disease. Given the differences in phage populations in healthy individuals versus those with cardiometabolic diseases such as T2D, we here questioned whether phages from T2D individuals would have increased immunogenic potential. To address this, we isolated intestinal phages from a fresh stool sample of healthy controls and individuals with newly diagnosed, treatment-naive T2D. Phages were purified using cesium chloride ultracentrifugation and incubated with healthy donor dendritic cells (DCs) and autologous T cells. Donors with T2D had slightly higher free viral particle numbers compared to healthy controls (p = .1972), which has been previously associated with disease states. Further, phages from T2D induced a higher inflammatory response in DCs and T cells than phages from HC. For example, the expression of the co-stimulatory molecule CD86 on DCs (p < .001) and interferon-y secretion from T cells (p < .01) were increased when comparing the two groups. These results suggest that phages might play a role in low-grade inflammation in T2D individuals.
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Bacteriófagos , Técnicas de Cocultura , Células Dendríticas , Diabetes Mellitus Tipo 2 , Inflamação , Humanos , Diabetes Mellitus Tipo 2/imunologia , Células Dendríticas/imunologia , Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Masculino , Pessoa de Meia-Idade , Inflamação/imunologia , Inflamação/virologia , Feminino , Fezes/virologia , Fezes/microbiologia , Adulto , Microbioma Gastrointestinal , Linfócitos T/imunologia , Idoso , Antígeno B7-2/metabolismoRESUMO
BACKGROUND: Glycemic control is an important goal of bariatric surgery in patients with type 2 diabetes mellitus (T2DM) and obesity. The laparoscopic one-anastomosis gastric bypass (OAGB) has potential metabolic benefits over the laparoscopic Roux-en-Y gastric bypass (RYGB). Aim of this study is to examine whether RYGB or OAGB grants better glycemic control 12 months post-surgery. METHODS: For this retrospective cohort study, patients with T2DM and obesity, who underwent primary OAGB between 2008 and 2017 were reviewed. For each OAGB patient, three primary RYGB patients were matched for age, gender and body mass index (BMI). Glycemic control was expressed by the glycated hemoglobin (HbA1c), which was measured pre- and 12 months post-operatively. Weight loss was reported in percentage total weight loss (%TWL). RESULTS: A total of 152 patients, of whom 38 had OAGB and 114 RYGB, were included. Mean (standard deviation (SD)) HbA1c was 7.49 (1.51)% in the OAGB group and 7.56(1.23)% in the RYGB group at baseline. Twelve months after surgery the mean (SD) HbA1c dropped to 5.73 (0.71)% after OAGB and 6.09 (0.76)% after RYGB (adjusted p = 0.011). The mean (SD) BMI was reduced from 42.5(6.3) kg/m2 to 29.6(4.7) kg/m2 after OAGB and 42.3(5.8) kg/m2 to 29.9 (4.5) kg/m2 after RYGB; reflecting 30.3 (6.8) %TWL post-OAGB and 29.0 (7.3) %TWL post-RYGB (p = 0.34). CONCLUSION: This study indicates that OAGB leads to lower HbA1c one year after surgery compared to RYGB, without a difference in weight loss. Prospective (randomized) studies are needed to ascertain the most optimal metabolic treatment for patients with obesity and T2DM.
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Diabetes Mellitus Tipo 2 , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Hemoglobinas Glicadas , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Estudos Prospectivos , Estudos de Coortes , Obesidade/cirurgia , Obesidade/etiologia , Redução de PesoRESUMO
BACKGROUND: Abdominal pain after bariatric surgery (BS) is frequently observed. Despite numerous diagnostic tests, the cause of abdominal pain is not always found. OBJECTIVES: To quantify type and number of diagnostic tests performed in patients with abdominal pain after BS and evaluate the burden and their yield in the diagnostic process. SETTING: A bariatric center in the Netherlands. METHODS: In this prospective study, we included patients who presented with abdominal pain after BS between December 1, 2020, and December 1, 2021. All diagnostic tests and reoperations performed during one episode of abdominal pain were scored using a standardized protocol. RESULTS: A total of 441 patients were included; 401 (90.9%) were female, median time after BS was 37.0 months (IQR, 11.0-66.0) and mean percentage total weight loss was 31.41 (SD, 10.53). In total, 715 diagnostic tests were performed, of which 355 were abdominal CT scans, 155 were ultrasounds, and 106 were gastroscopies. These tests yielded a possible explanation for the pain in 40.2% of CT scans, 45.3% of ultrasounds, and 34.7% of gastroscopies. The diagnoses of internal herniation, ileus, and nephrolithiasis generally required only 1 diagnostic test, whereas patients with anterior cutaneous nerve entrapment syndrome, irritable bowel syndrome, and constipation required several tests before diagnosis. Even after several negative tests, a diagnosis was still found in the subsequent test: 86.7% of patients with 5 or more tests had a definitive diagnoses. Reoperations were performed in 37.2% of patients. CONCLUSION: The diagnostic burden in patients with abdominal pain following BS is high. The most frequently performed diagnostic test is an abdominal CT scan, yielding the highest number of diagnoses in these patients.
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Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Feminino , Masculino , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/complicações , Estudos Prospectivos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Cirurgia Bariátrica/efeitos adversos , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/cirurgia , Laparoscopia/métodosRESUMO
Weight regain or inadequate weight loss following Roux-en-Y gastric bypass poses a significant clinical challenge. Our objective was to evaluate various revisional techniques for addressing weight regain and insufficient weight loss after Roux-en-Y gastric bypass through a systematic review and meta-analysis. We performed a literature search (in PubMed and Embase) on revisional interventions in collaboration with a medical information specialist. Measured outcomes included body mass index at intervention, total weight loss during follow-up, and complications. Random effects models were used to determine pooled effect size and corresponding 95% confidence intervals. Thirty-nine studies were included: four studies reported on argon plasma coagulation, four studies on transoral outlet reduction, nine studies on transoral outlet reduction + argon plasma coagulation, four studies on pouch/gastrojejunal anastomosis revision, five on laparoscopic gastric banding, two studies on laparoscopic gastric banding + pouch resizing, 10 on distalization-RYGB, and one on duodenal switch. All techniques resulted in short-term clinically relevant weight loss. Endoscopic procedures had a short follow-up and resulted in modest and temporary weight loss. Surgical revision techniques were successful for weight loss in longer term follow-up, at the expense of high complication rates.
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Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Reoperação/métodos , Laparoscopia/métodos , Redução de Peso , Aumento de Peso , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Roux-en-Y gastric bypasses (RYGB) are frequently accompanied by long-term gastrointestinal (GI) symptoms. Direct mechanistic insight into the causation of these symptoms is lacking, but changes in the intestinal microbiome have been proposed to play a role. With this study, we aimed to investigate whether a microbial predisposition exists before RYGB which is associated with GI symptoms during follow-up and to evaluate which microbial groups are involved. MATERIALS AND METHODS: In total, 67 RYGB patients were included. Shotgun metagenomic sequencing was performed on fecal samples obtained just before and 1 year after surgery. To assess GI symptoms, patients filled out Gastrointestinal Quality of Life Index (GIQLI) questionnaires and were divided into groups based on their total GIQLI score and change in score (postsurgery versus baseline). Extremely randomized tree predictor models were used to identify the most distinctive microbial species associated with postoperative GI symptoms. RESULTS: Beta diversity differed significantly between baseline and 1-year post-surgery samples, with the post-surgery microbiome resembling a more dysbiotic profile. The most predictive species regarding total GIQLI (AUC 0.77) or delta GIQLI score (AUC 0.83) were identified. Many of these species are known butyrate producers or species known to support them and/or species with anti-inflammatory properties, including Coprococcus eutactus, Faecalibacterium prausnitzii, and Ruminococcus callidus. CONCLUSION: Beneficial commensal gut microbiota related to a high GI score were associated to adequate intestinal fermentative capacity, suggesting these species might have protective properties against postoperative GI malfunctioning.
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Derivação Gástrica , Microbioma Gastrointestinal , Microbiota , Obesidade Mórbida , Humanos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Qualidade de VidaRESUMO
Weight loss through bariatric surgery is efficient for treatment or prevention of obesity related diseases such as type 2 diabetes and cardiovascular disease. Long term weight loss response does, however, vary among patients undergoing surgery. Thus, it is difficult to identify predictive markers while most obese individuals have one or more comorbidities. To overcome such challenges, an in-depth multiple omics analyses including fasting peripheral plasma metabolome, fecal metagenome as well as liver, jejunum, and adipose tissue transcriptome were performed for 106 individuals undergoing bariatric surgery. Machine leaning was applied to explore the metabolic differences in individuals and evaluate if metabolism-based patients' stratification is related to their weight loss responses to bariatric surgery. Using Self-Organizing Maps (SOMs) to analyze the plasma metabolome, we identified five distinct metabotypes, which were differentially enriched for KEGG pathways related to immune functions, fatty acid metabolism, protein-signaling, and obesity pathogenesis. The gut metagenome of the most heavily medicated metabotypes, treated simultaneously for multiple cardiometabolic comorbidities, was significantly enriched in Prevotella and Lactobacillus species. This unbiased stratification into SOM-defined metabotypes identified signatures for each metabolic phenotype and we found that the different metabotypes respond differently to bariatric surgery in terms of weight loss after 12 months. An integrative framework that utilizes SOMs and omics integration was developed for stratifying a heterogeneous bariatric surgery cohort. The multiple omics datasets described in this study reveal that the metabotypes are characterized by a concrete metabolic status and different responses in weight loss and adipose tissue reduction over time. Our study thus opens a path to enable patient stratification and hereby allow for improved clinical treatments.
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Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/cirurgia , Obesidade/cirurgia , Tecido Adiposo , AlgoritmosRESUMO
Obesity and diabetes are associated with inflammation and altered plasma levels of several metabolites, which may be involved in disease progression. Some metabolites can activate G protein-coupled receptors (GPCRs) expressed on immune cells where they can modulate metabolic inflammation. Here, we find that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes (T2D) compared with nondiabetic controls. Administration of 3-hydroxydecanoate to mice promotes immune cell recruitment to adipose tissue, which was associated with adipose inflammation and increased fasting insulin levels. Furthermore, we demonstrate that 3-hydroxydecanoate stimulates migration of primary human and mouse neutrophils, but not monocytes, through GPR84 and Gαi signaling in vitro. Our findings indicate that 3-hydroxydecanoate is a T2D-associated metabolite that increases inflammatory responses and may contribute to the chronic inflammation observed in diabetes.
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Conscience is a diagnostically relevant concept in forensic psychiatry, but often misinterpreted as an all-or-none phenomenon. We conceptualize the conscience as a psychic function in which elements like empathy, self-conscience emotions such as shame, guilt and pride, and moral orientation work together. The differences in conscience functioning can be described in terms of developmental levels of integration. We conducted network analyses on data collected via a questionnaire survey held among 52 offending and 243 non-offending juveniles. We displayed two networks: One representing the non-offenders' normative and one representing the offenders' defiantly maturing conscience. As was hypothesized, in the non-offenders network, almost all elements clustered into one clinically meaningful network, indicating integration of the different elements of the normative maturing conscience. In the offenders network, the correlations between the elements were sporadic, indicating a lack of integration of the defiantly maturing conscience. The difference between the two networks was more prominent for empathy and moral orientation than for self-conscious emotions. This research supports the theory of differences in maturation of conscience instead of being an all-or-none phenomenon and calls for further research, taking a deeper look at the significance of integration of the conscience and its implications for offending behaviour.
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To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10-5) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.
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Microbiota , Hepatopatia Gordurosa não Alcoólica , Álcool Desidrogenase , Antibacterianos , Etanol , Humanos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Estudos ProspectivosRESUMO
Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.
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Diabetes Mellitus Tipo 2 , Flagelina , Microbioma Gastrointestinal , Células Secretoras de Insulina , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Flagelina/genética , Flagelina/metabolismo , Humanos , Inflamação/metabolismo , Insulina , Células Secretoras de Insulina/metabolismo , CamundongosRESUMO
Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors and may contribute to development of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). In this article, we investigated whether chronically elevated insulin levels are associated with cellular senescence in the human liver. In 107 individuals undergoing bariatric surgery, hepatic senescence markers were assessed by immunohistochemistry as well as transcriptomics. A subset of 180 participants from the ongoing Finnish Kuopio OBesity Surgery (KOBS) study was used as validation cohort. We found plasma insulin to be highly associated with various markers of cellular senescence in liver tissue. The liver transcriptome of individuals with high insulin revealed significant upregulation of several genes associated with senescence: p21, TGFß, PI3K, HLA-G, IL8, p38, Ras, and E2F. Insulin associated with hepatic senescence independently of NAFLD and plasma glucose. By using transcriptomic data from the KOBS study, we could validate the association of insulin with p21 in the liver. Our results support a potential role for hyperinsulinemia in induction of cellular senescence in the liver. These findings suggest possible benefits of lowering insulin levels in obese individuals with insulin resistance.
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Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Diabetes Mellitus Tipo 2/complicações , Humanos , Hiperinsulinismo/complicações , Insulina , Fígado , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
Weight failure after sleeve gastrectomy (SG) is frequently observed. Consensus on the most effective treatment is lacking. The aim of this meta-analysis was to assess revisional strategies for weight regain (WR) or insufficient weight loss (IWL) following SG. The included studies reported on endoscopic gastroplasty (ESG), re-sleeve gastrectomy (re-SG), Roux-en-Y gastric bypass (RYGB), one-anastomosis gastric bypass (OAGB), single-anastomosis duodeno-ileal bypass (SADI), and duodenal switch (DS). All techniques resulted in clinically relevant weight loss. Although our data suggest that revisional OAGB was the most effective procedure, the lack of direct comparisons precludes strong conclusions. All procedures were feasible but differed regarding complication rates. Choice of procedure is depending on patient's characteristics and surgeons' expertise.
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Derivação Gástrica , Obesidade Mórbida , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Derivação Gástrica/métodos , Humanos , Obesidade Mórbida/cirurgia , Reoperação , Estudos Retrospectivos , Aumento de Peso , Redução de PesoRESUMO
Obesity and type 2 diabetes (T2D) are growing burdens for individuals and the health-care system. Bariatric surgery is an efficient, but drastic treatment to reduce body weight, normalize glucose values, and reduce low-grade inflammation. The gut microbiome, which is in part controlled by intestinal antibodies, such as IgA, is involved in the development of both conditions. Knowledge of the effect of bariatric surgery on systemic and intestinal antibody response is limited. Here, we determined the fecal antibody and gut microbiome response in 40 T2D and non-diabetic (ND) obese individuals that underwent bariatric surgery (N = 40). Body weight, fasting glucose concentrations and inflammatory parameters decreased after bariatric surgery, whereas pro-inflammatory bacterial species such as lipopolysaccharide (LPS), and flagellin increased in the feces. Simultaneously, concentrations of LPS- and flagellin-specific intestinal IgA levels increased with the majority of pro-inflammatory bacteria coated with IgA after surgery. Finally, serum antibodies decreased in both groups, along with a lower inflammatory tone. We conclude that intestinal rearrangement by bariatric surgery leads to expansion of typical pro-inflammatory bacteria, which may be compensated by an improved antibody response. Although further evidence and mechanistic insights are needed, we postulate that this apparent compensatory antibody response might help to reduce systemic inflammation by neutralizing intestinal immunogenic components and thereby enhance intestinal barrier function after bariatric surgery.
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Anticorpos Antibacterianos/sangue , Bactérias/imunologia , Diabetes Mellitus Tipo 2/imunologia , Microbioma Gastrointestinal , Intestinos/microbiologia , Obesidade/imunologia , Anticorpos Antibacterianos/imunologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Cirurgia Bariátrica , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/cirurgia , Fezes/química , Fezes/microbiologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Intestinos/imunologia , Obesidade/sangue , Obesidade/microbiologia , Obesidade/cirurgiaRESUMO
BACKGROUND: Chronic abdominal complaints after bariatric surgery may be explained by pancreatic exocrine insufficiency (PEI). OBJECTIVES: We aimed to evaluate the clinical value of the Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) as a screening tool to identify patients with a high probability of having PEI. SETTING: Outpatient clinic for bariatric surgery. METHODS: Patients scheduled for a screening or follow-up appointment were asked to complete the PEI-Q and the Gastrointestinal Quality of Life Index questionnaire (GIQLI). Postoperative patients with a high PEI-Q score (0,6) were offered a fecalelastase (FE) test (abnormal if <200 µg/g). RESULTS: Between June 2020 and February 2021, a total of 1600 of 1629 PEI-Qs were completed, 1073 (67%) of which after surgery. The postoperative group consisted mostly of females (81.9%), aged 49.0 ± 10.6 years, with a total weight loss of 30.3% ± 8.8%. Among them, 63.4% had abnormal PEI-Q scores compared with 34.9% before surgery (P < .01). In contrast, the median GIQLI score increased (119 [interquartile range (IQR), 107-129.25] versus 110 [IQR, 95-121.75]) before surgery (P < .01). Additionally, 310 FE tests were performed, of which only 11.9% was suggestive of PEI. No correlation was found between the PEI-Q scores and FE levels (c-index .55). CONCLUSION: The PEI-Q in its current version is not able to distinguish complaints of PEI and bariatric surgery itself and therefore cannot be used as a screening tool for PEI. The specificity of the FE test seems to be reduced after surgery. Future research should include a more direct pancreatic function test, which may provide more insight into PEI after bariatric surgery.
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Cirurgia Bariátrica , Insuficiência Pancreática Exócrina , Adulto , Cirurgia Bariátrica/efeitos adversos , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Redução de PesoRESUMO
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing, as are other manifestations of metabolic syndrome such as obesity and type 2 diabetes. NAFLD is currently the number one cause of chronic liver disease worldwide. The pathophysiology of NAFLD and disease progression is poorly understood. A potential contributing role for gut microbiome and metabolites in NAFLD is proposed. Currently, bariatric surgery is an effective therapy to prevent the progression of NAFLD and other manifestations of metabolic syndrome such as obesity and type 2 diabetes. This review provides an overview of gut microbiome composition and related metabolites in individuals with NAFLD and after bariatric surgery. Causality remains to be proven. Furthermore, the clinical effects of bariatric surgery on NAFLD are illustrated. Whether the gut microbiome and metabolites contribute to the metabolic improvement and improvement of NAFLD seen after bariatric surgery has not yet been proven. Future microbiome and metabolome research is necessary for elucidating the pathophysiology and underlying metabolic pathways and phenotypes and providing better methods for diagnostics, prognostics and surveillance to optimize clinical care.
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PURPOSE: The importance of follow-up (FU) for midterm weight loss (WL) after bariatric surgery is controversial. Compliance to this FU remains challenging. Several risk factors for loss to FU (LtFU) have been mentioned. The aim was therefore to evaluate the association between WL and LtFU 3 to 5 years postoperatively and to identify risk factors for LtFU. MATERIALS AND METHODS: A single-center cross-sectional study in the Netherlands. Between June and October 2018, patients scheduled for a 3-, 4-, or 5-year FU appointment were included into two groups: compliant (to their scheduled appointment and overall maximally 1 missed appointment) and non-compliant (missed the scheduled appointment and at least 1 overall). Baseline, surgical, and FU characteristics were collected and a questionnaire concerning socio-economic factors. RESULTS: In total, 217 patients in the compliant group and 181 in the non-compliant group were included with a median body mass index at baseline of 42.0 and 42.9 respectively. Eighty-eight percent underwent a laparoscopic Roux-en-Y gastric bypass. The median percentage total weight loss for the compliant and non-compliant groups was 30.7% versus 28.9% at 3, 29.3% versus 30.2% at 4, and 29.6% versus 29.9% at 5 years respectively, all p>0.05. Age, persistent comorbidities and vitamin deficiencies, a yearly salary <20,000 euro, no health insurance coverage, and not understanding the importance of FU were risk factors for LtFU. CONCLUSION: Three to 5 years postoperatively, there is no association between LtFU and WL. The compliant group demonstrated more comorbidities and vitamin deficiencies. Younger age, not understanding the importance of FU, and financial challenges were risk factors for LtFU.
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Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Índice de Massa Corporal , Estudos Transversais , Seguimentos , Gastrectomia , Humanos , Países Baixos/epidemiologia , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
OBJECTIVE: Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects. DESIGN: Subjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks. RESULTS: We observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa. CONCLUSION: Allogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects. TRIAL REGISTRATION NUMBER: NTR4327.
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Transplante de Microbiota Fecal , Derivação Gástrica , Glucose/metabolismo , Resistência à Insulina , Síndrome Metabólica/metabolismo , Adulto , Idoso , Ácidos e Sais Biliares/análise , Quimiocina CCL2/sangue , Quimiocina CCL2/genética , Metabolismo Energético , Ácidos Graxos Voláteis/análise , Fezes/química , Microbioma Gastrointestinal , Trânsito Gastrointestinal , Expressão Gênica , Humanos , Lipólise , Masculino , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/terapia , Metabolômica , Pessoa de Meia-Idade , Gordura Subcutânea/metabolismo , Doadores de Tecidos , Adulto JovemRESUMO
BACKGROUND: The laparoscopic Roux-en-Y gastric bypass (LRYGBP) is the second most performed bariatric surgical procedure. With the increasing number of patients undergoing bariatric surgery, the number of complications is also growing. Early diagnosis and treatment of the complications is crucial. CASE PRESENTATION: A very unusual complication was met after an uneventful laparoscopic gastric bypass (LGBP) procedure due to an obstructing blood clot in the biliairy limb resulting in an acute pancreatitis and gastric distention, accompanied by an obstructing blood clot in the distal ileum causing small bowel obstruction. A review of the occurrence of these complications and the diagnosis and treatment is presented. CONCLUSION: Post-bariatric acute pancreatitis is uncommon, but could be fatal. Blood clots should be considered as possible causes of small bowel obstruction, ileus or pancreatitis.
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Derivação Gástrica/efeitos adversos , Doenças do Íleo/etiologia , Obstrução Intestinal/etiologia , Laparoscopia/efeitos adversos , Pancreatite/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Feminino , Humanos , Doenças do Íleo/diagnóstico por imagem , Doenças do Íleo/terapia , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/terapia , Obesidade Mórbida/cirurgia , Pancreatite/diagnóstico por imagem , Pancreatite/terapia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/terapia , Tomografia Computadorizada por Raios XRESUMO
Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal , Imidazóis/metabolismo , Insulina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Transdução de Sinais , Animais , Células Cultivadas , Diabetes Mellitus Tipo 2/microbiologia , Células HEK293 , Histidina/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Sequestossoma-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: A learning curve (LC) is a graphic display of the number of consecutive procedures performed necessary to reach competence and is defined by complications and duration of surgery (DOS). There is little evidence on the LC of surgical residents in bariatric surgery. Aim of the study is to evaluate whether the laparoscopic Roux-en-Y gastric bypass (LRYGB) can be safely performed by surgical residents, to evaluate the LC of surgical residents for LRYGB and to assess whether surgical residents fit in the LC of the bariatric center which has been established by their proctors. METHODS: Records of all 3389 consecutive primary LRYGB patients, operated between December 2007 and January 2016 in a bariatric center-of-excellence in Amsterdam, were reviewed. Differences in DOS were assessed by means of a linear regression model. Differences in complications (classified as Clavien-Dindo ≥ 2) were evaluated with the χ 2 or the Fisher exact test. Cases were clustered in groups of 70 for comparison and reported for residents with ≥70 cases as primary surgeon. RESULTS: Four surgeons (S1-4) and three residents (R1-3) performed 2690 (88.2%) and 361 (11.8%) of 3051 LRYGBs, respectively. Median (IQR) DOS was 52.0 (42.0-65.0) min for S1-4 versus 53.0 (46.0-63.0) min for R1-3 (p = 0.52). The LC of R1-3 in their first 70 cases (n = 210) differs significantly from the individual (n = 70) LCs of surgeon 1, 2, and 3, with remarkably shorter DOS for the residents (adjusted p < 0.0001; p < 0.001 and p = 0.0002, respectively) and the same amount of surgical complications 5.1% (137/2690) for S1-4 versus 3.0% (11/361) for R1-3 (p = 0.089). CONCLUSION: Laparoscopic Roux-en-Y gastric bypass can be safely performed by surgical residents under supervision of experienced bariatric surgeons. Surgical residents benefit from the experience of their proctors and they fit faultlessly in the LC of the surgical team, as set out by their proctors in a large bariatric center-of-excellence.