Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity.

AIMS: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. MATERIAL AND METHODS: Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. RESULTS: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. CONCLUSIONS: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. METHODS: This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. FINDINGS: Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. INTERPRETATION: Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. FUNDING: The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.

Upper endoscopy after Roux-en-Y gastric bypass: diagnostic yield and factors associated with relevant findings.

BACKGROUND: After laparoscopic Roux-en-Y gastric bypass many patients present with complaints for which an upper endoscopy is performed. However, often no abnormalities are found. OBJECTIVES: To investigate the incidence of relevant findings at upper endoscopy and identify patient characteristics associated with a relevant finding. SETTING: A high-volume bariatric center. METHODS: A retrospective cohort study was performed. All patients presenting with complaints after laparoscopic Roux-en-Y gastric bypass who consequently underwent a diagnostic upper endoscopy were identified from a prospective endoscopic database. Primary outcomes were the number and type of relevant findings at upper endoscopy and its association with patient characteristics. Relevant findings were defined as abnormalities requiring treatment. RESULTS: Ninety-eight (39.2%) of 250 patients had a relevant finding at upper endoscopy, mostly marginal ulcer and stomal stenosis. Male sex (odds ratio [OR] 3.47 [1.12-10.76]), alcohol consumption (OR 7.27 [1.58-33.36]), dysphagia or suspicion of bleeding as referral reason (OR 3.62 [1.54-8.52] and 39.93 [4.96-321.47], respectively, compared with abdominal pain), an abnormal upper gastrointestinal series (OR 6.81 [2.06-22.48]), and no abdominal ultrasound (OR 7.41 [1.48-37.08] compared with a normal ultrasound) were significantly associated with a relevant finding at upper endoscopy. CONCLUSIONS: In this study sex, alcohol consumption, referral reason, and prior imaging studies were associated with a relevant finding at upper endoscopy after laparoscopic Roux-en-Y gastric bypass.

Gastrointestinal symptoms before and after laparoscopic Roux-en-Y gastric bypass: a longitudinal assessment.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective treatment for morbid obesity, but many patients have increased gastrointestinal symptoms. OBJECTIVES: To evaluate gastrointestinal symptoms and food intolerance before and after RYGB over time in a large cohort of morbidly obese patients. SETTING: A high-volume bariatric center of excellence. METHODS: A prospective cohort study was performed in patients who underwent RYGB between September 2014 and July 2015, with 2-year follow-up. Consecutive patients screened for bariatric surgery answered the Gastrointestinal Symptom Rating Scale (GSRS) and a food intolerance questionnaire before RYGB and 2 years after surgery. The prevalence of gastrointestinal symptoms before and after surgery and the association between patient characteristics and postoperative gastrointestinal symptoms were assessed. RESULTS: Follow-up was 86.2% (n = 168) for patients undergoing primary RYGB and 93.3% (n = 28) for revisional RYGB. The total mean GSRS score increased from 1.69 to 2.31 after surgery (P < .001), as did 13 of 16 of the individual scores. Preoperative GSRS score is associated with postoperative symptom severity (B = .343, P < .001). Food intolerance was present in 16.1% of patients before primary RYGB, increasing to 69.6% after surgery (P < .001). Patients who underwent revisional RYGB had a symptom severity and prevalence of food intolerance comparable with that among patients with primary RYGB, even though they had more symptoms before revisional surgery. CONCLUSIONS: Two years after surgery, patients who underwent primary RYGB have increased gastrointestinal symptoms and food intolerance compared with the preoperative state. It is important that clinicians are aware of this and inform patients before surgery.

A novel fully covered double-bump stent for staple line leaks after bariatric surgery: a retrospective analysis.

BACKGROUND: Staple line leakage after bariatric surgery can be treated by endoscopic placement of a self-expandable stent. The success rate of stent placement is generally high, but migration is a frequent adverse event that hampers successful treatment. The Niti-S Beta stent is a fully covered double-bump stent that was specifically designed to prevent migration. This study aimed to evaluate the effectiveness and adverse event rate of the Niti-S Beta stent. METHODS: A retrospective study was performed in three high-volume bariatric centers. All consecutive patients between 2009 and 2016 who underwent placement of a Beta stent for staple line leakage were included. Primary outcome was resolution of the leakage; secondary outcome was the adverse event rate including migration. RESULTS: Thirty-eight patients were included. Twenty-five (66%) had resolution of the leakage. Success rate was higher in patients who were treated with implantation of a Beta stent as initial treatment (100%) than in patients who were treated with a stent after revisional surgery had failed (55%, p = 0.013). Migration occurred in 12 patients (32%). There were two severe adverse events requiring surgical intervention, including a bleeding from an aorto-esophageal fistula. CONCLUSIONS: The success rate and the migration rate of the Beta stent seem comparable to other stents in this retrospective study. Despite the novel double-bump structure of the stent, the migration rate does not seem to be decreased.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial).

BACKGROUND: The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA. METHODS: A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed. DISCUSSION: The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective. TRIAL REGISTRATION: Netherlands Trial Register (trialregister.nl) 6135 . Date registered: 21-Nov-2016.

Fecal Calprotectin, Elastase, and Alpha-1-Antitrypsin Levels After Roux-en-Y Gastric Bypass; Calprotectin Is Significantly Elevated in the Majority of Patients.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) causes several alterations in gastrointestinal function. We hypothesized that levels of three commonly used fecal tests change after RYGB. METHODS: Fecal levels of calprotectin, elastase, and alpha-1-antitrypsin were determined in 122 patients without signs of gastrointestinal disease 1 to 2 years after RYGB. Medians, distribution of values, and the percentage of patients with levels above or below reference values were determined. RESULTS: Median fecal calprotectin level was 163.5 (<30-1587) µg/g; in 87 % of patients, it was above the reference value (<50 µg/g). Median fecal elastase level was 444 (<15-647) µg/g; 13 % was below the reference value (>200 µg/g). Median fecal alpha-1-antitrypsin level was 0.51 (<0.20-2.20) mg/g, comparable to the reference values. CONCLUSIONS: Fecal calprotectin levels are significantly higher than the reference value in most patients after RYGB. Fecal elastase is significantly lower. This might indicate that the validity of fecal calprotectin testing is impaired after RYGB and the specificity for fecal elastase is decreased. Clinical awareness of altered fecal markers after RYGB is essential to prevent unnecessary diagnostic tests, such as colonoscopy. Fecal alpha-1-antitrypsin is not influenced by RYGB.

Proton Pump Inhibitor Prophylaxis After Gastric Bypass Does Not Cause Hypomagnesemia.

Proton pump inhibitor (PPI)-induced hypomagnesemia is currently a major topic. Patients undergoing Roux-en-Y gastric bypass are generally prescribed PPI prophylaxis after surgery. We investigated the prevalence of hypomagnesemia in our bariatric population. We reviewed the files of 1000 postoperative patients for serum magnesium level during PPI use. We found only five cases of hypomagnesemia, none of which was evidently related to PPI use. We conclude that the risk of hypomagnesemia during 1 year of prophylactic PPI use after Roux-en-Y gastric bypass (RYGB) is minimal and laboratory screening is probably not necessary.