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Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.
Mocanu, V, Zhang, Z, Deehan, EC, Kao, DH, Hotte, N, Karmali, S, Birch, DW, Samarasinghe, KK, Walter, J, Madsen, KL
Nature medicine. 2021;(7):1272-1279
Abstract
Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n = 17), FMT-LF (n = 17), HF (n = 17) and LF (n = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome.
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The Impact of Proximal Roux-en-Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism.
Chen, KF, Chan, LN, Senn, TD, Oelschlager, BK, Flum, DR, Shen, DD, Horn, JR, Lin, YS
Pharmacotherapy. 2020;(3):191-203
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGBS), a surgery that creates a smaller stomach pouch and reduces the length of small intestine, is one of the most common medical interventions for the treatment of obesity. AIM: The aim of this study was to determine how RYGBS affects the absorption and metabolism of acetaminophen. MATERIALS AND METHODS Ten morbidly obese patients received 1.5 g of liquid acetaminophen (APAP) orally on three separate pharmacokinetic study days (i.e., pre-RYGBS baseline and 3 and 12 months post-RYGBS). Plasma was collected at pre-specified timepoints over 24 hours, and the samples were analyzed using liquid chromatography-mass spectrometry for APAP, APAPglucuronide (APAP-gluc), APAP-sulfate (APAP-sulf), APAP-cysteine (APAP-cys), and APAP-Nacetylcysteine (APAP-nac). RESULT Following RYGBS, peak APAP concentrations at the 3-month and 12-month visits increased by 2.0-fold compared to baseline (p=0.0039 and p=0.0078, respectively) and the median time to peak concentration decreased from 35 to 10 minutes. In contrast, peak concentrations of APAP-gluc, APAP-sulf, APAP-cys, and APAP-nac were unchanged following RYGBS. The apparent oral clearance of APAP and the ratios of metabolite area under the curve (AUC)-to-APAP AUC for all four metabolites decreased at 3 and 12 months post-RYGBS compared to the presurgical baseline. In a simulation of expected steady-state plasma concentrations following multiple dosing of 650 mg APAP every 4 hours, post-RYGBS patients had higher steady-state peak APAP concentrations compared to healthy individuals and obese pre-RYGBS patients, though APAP exposure was unchanged compared to healthy individuals. CONCLUSION Following RYGBS, the rate and extent of APAP absorption increased and decreased formation of APAP metabolites was observed, possibly due to downregulation of Phase II and cytochrome P450 2E1 enzymes.
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Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for obesity (YOMEGA): a multicentre, randomised, open-label, non-inferiority trial.
Robert, M, Espalieu, P, Pelascini, E, Caiazzo, R, Sterkers, A, Khamphommala, L, Poghosyan, T, Chevallier, JM, Malherbe, V, Chouillard, E, et al
Lancet (London, England). 2019;(10178):1299-1309
Abstract
BACKGROUND One anastomosis gastric bypass (OAGB) is increasingly used in the treatment of morbid obesity. However, the efficacy and safety outcomes of this procedure remain debated. We report the results of a randomised trial (YOMEGA) comparing the outcomes of OAGB versus standard Roux-en-Y gastric bypass (RYGB). METHODS This prospective, multicentre, randomised non-inferiority trial, was held in nine obesity centres in France. Patients were eligible for inclusion if their body-mass index (BMI) was 40 kg/m2 or higher, or 35 kg/m2 or higher with the presence of at least one comorbidity (type 2 diabetes, high blood pressure, obstructive sleep apnoea, dyslipidaemia, or arthritis), and were aged 18-65 years. Key exclusion criteria were a history of oesophagitis, Barrett's oesophagus, severe gastro-oesophageal reflux disease resistant to proton-pump inhibitors, and previous bariatric surgery. Participants were randomly assigned (1:1) to OAGB or RYGB, stratified by centre with blocks of variable size; the study was open-label, with no masking required. RYGB consisted of a 150 cm alimentary limb and a 50 cm biliary limb and OAGB of a single gastrojejunal anastomosis with a 200 cm biliopancreatic limb. The primary endpoint was percentage excess BMI loss at 2 years. The primary endpoint was assessed in the per-protocol population and safety was assessed in all randomised participants. This study is registered with ClinicalTrials.gov, number NCT02139813, and is now completed. FINDINGS From May 13, 2014, to March 2, 2016, of 261 patients screened for eligibility, 253 (97%) were randomly assigned to OAGB (n=129) or RYGB (n=124). Five patients did not undergo their assigned surgery, and after undergoing their surgery 14 were excluded from the per-protocol analysis (seven due to pregnancy, two deaths, one withdrawal, and four revisions from OAGB to RYGB) In the per-protocol population (n=117 OAGB, n=117 RYGB), mean age was 43·5 years (SD 10·8), mean BMI was 43·9 kg/m2 (SD 5·6), 176 (75%) of 234 participants were female, and 58 (27%) of 211 with available data had type 2 diabetes. After 2 years, mean percentage excess BMI loss was -87·9% (SD 23·6) in the OAGB group and -85·8% (SD 23·1) in the RYGB group, confirming non-inferiority of OAGB (mean difference -3·3%, 95% CI -9·1 to 2·6). 66 serious adverse events associated with surgery were reported (24 in the RYGB group vs 42 in the OAGB group; p=0·042), of which nine (21·4%) in the OAGB group were nutritional complications versus none in the RYGB group (p=0·0034). INTERPRETATION OAGB is not inferior to RYGB regarding weight loss and metabolic improvement at 2 years. Higher incidences of diarrhoea, steatorrhoea, and nutritional adverse events were observed with a 200 cm biliopancreatic limb OAGB, suggesting a malabsorptive effect. FUNDING French Ministry of Health.
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Preoperative weight loss program involving a 20-day very low-calorie diet for obesity before laparoscopic gastrectomy for gastric cancer.
Inoue, K, Yoshiuchi, S, Yoshida, M, Nakamura, N, Nakajima, S, Kitamura, A, Mouri, K, Michiura, T, Mukaide, H, Ozaki, T, et al
Asian journal of endoscopic surgery. 2019;(1):43-50
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Abstract
INTRODUCTION The increased visceral fat in patients with obesity can increase the technical difficulty of surgery. This study was performed to evaluate a preoperative 20-day very low-calorie diet for obesity before laparoscopic gastrectomy for gastric cancer. METHODS This prospective single-center study involved patients with obesity who were planning to undergo laparoscopic gastrectomy for gastric cancer. Obesity was defined according to the Japanese criteria: BMI ≥25 kg/m2 or waist circumference ≥85 cm in men and ≥90 cm in women. The patients underwent a preoperative 20-day very low-calorie diet and received nutritional counseling. Weight loss, body composition, visceral fat mass, and operative outcomes were evaluated. RESULTS Thirty-three patients were enrolled from September 2013 to August 2015. Their median age was 71 years, and 78.8% were men. Their median bodyweight and BMI were 72.3 kg (range, 53.8-82.5 kg) and 26.0 kg/m2 (range, 23.5-31.0 kg/m2 ), respectively. The patients achieved a mean weight loss of 4.5% (95% confidence interval [CI]: 3.8-5.1), corresponding to 3.2 kg (95%CI: 2.7-3.7 kg). Body fat mass was significantly decreased by a mean of 2.5 kg (95%CI: 1.9-3.1), whereas skeletal muscle mass was unaffected (mean: -0.20 kg [95%CI: -0.55-0.15]). The visceral fat mass reduction rate was high as 16.8% (range, 11.6%-22.0%). All patients underwent laparoscopic gastrectomy as planned. Severe postoperative morbidity (Clavien-Dindo grade ≥III) was seen in only one patient (3.0%). CONCLUSION The preoperative 20-day very low-calorie diet weight loss program is promising for the treatment of obesity before laparoscopic gastrectomy for gastric cancer.
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Laparoscopic Roux-en-Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates.
Puris, E, Pasanen, M, Ranta, VP, Gynther, M, Petsalo, A, Käkelä, P, Männistö, V, Pihlajamäki, J
Basic & clinical pharmacology & toxicology. 2019;(2):123-132
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Abstract
There is a lack of information about the changes in drug pharmacokinetics and cytochrome P450 (CYP) metabolism after bariatric surgery. Here, we investigated the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery on pharmacokinetics of nine drugs given simultaneously which may reveal changes in the activities of the main CYPs. Eight obese subjects undergoing LRYGB received an oral cocktail containing nine drugs, substrates of various CYPs: melatonin (CYP1A2), nicotine (CYP2A6), bupropion (CYP2B6), repaglinide (CYP2C8), losartan (CYP2C9), omeprazole (CYP2C19/CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A). The 6-hours pharmacokinetic profiles in serum and urine of each drug or corresponding metabolite as well as their metabolic ratios were compared before surgery with those at a median 1 year later. LRYGB exerted variable effects on the pharmacokinetics of these drugs. The geometric mean AUC0-6 (90% confidence interval) of melatonin, bupropion, repaglinide, chlorzoxazone and midazolam after LRYGB was 27 (19%-41%), 54 (43%-67%), 44 (29%-66%), 160 (129%-197%) and 74 (62%-90%) of the pre-surgery values, respectively. The pharmacokinetics of losartan, omeprazole and dextromethorphan did not change in response to surgery. Nicotine was not detected in serum, while geometric mean of AUC0-6 of its metabolite, cotinine, increased by 1.7 times after surgery. There were 3.6- and 1.3-fold increases in the AUC ratios of 6-hydroxymelatonin/melatonin and hydroxybupropion/bupropion, respectively. The cocktail revealed multiple pharmacokinetic changes occurring after LRYGB with the greatest effects observed for CYP1A2, CYP2C8 and CYP2E1 substrates. Future studies should be focused on CYP1A2, CYP2A6, CYP2C8 and CYP2B6 to clarify the changes in activities of these enzymes after LRYGB.
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Using a Revised Protein-Sparing Modified Fast (rPSMF) for Children and Adolescents with Severe Obesity: A Pilot Study.
Eneli, I, Xu, J, Tindall, A, Watowicz, R, Worthington, J, Tanner, K, Pratt, K, Walston, M
International journal of environmental research and public health. 2019;(17)
Abstract
Treatment options are limited for children and adolescents with severe obesity. One alternative treatment is the protein-sparing modified fast (PSMF), a low-carbohydrate, high-protein diet that can result in substantial weight loss. The aim of the study is to evaluate the adherence and efficacy of a revised PSMF (rPSMF) for severe obesity in a pediatric tertiary care weight-management program. The rPSMF with 1200-1800 calories, 40-60 g of carbohydrate/day and 1.2-1.5 g protein/kg of ideal bodyweight was implemented over 12 months. Twenty-one participants enrolled in the study. Mean age 16.2 ± 1.4 years, females (76.2%) and mean weight at baseline was 119 ± 19.9 kg. Regardless of adherence to the rPSMF, the mean weight change at 1 month was -3.7 ± 3.5 kg, (range -13.5 kg to 0.9 kg); at 3 months was -5.5 ± 5.1 kg, (range -19.3 kg to 1.8 kg) and at 6 months was -4.7 ± 6.6 kg, (range -18.3 kg to 8.6 kg). At 12 months, the mean weight change was -1.3 ± 10.6 kg (range -17.7 kg to 14.8 kg). Parent and child-reported physical and psychosocial quality of life (HRQOL) improved. Despite limited adherence, the rPSMF diet resulted in clinically significant weight loss and improved HRQOL for children and adolescents with severe obesity.
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Totally endoscopic implant to effect a gastric bypass: 12-month safety and efficacy outcomes.
Sandler, BJ, Biertho, L, Anvari, M, Rumbaut, R, Morales-Garza, LA, Torres-Barrera, G, Marceau, S, Hong, D, Smith, CD, Horgan, S
Surgical endoscopy. 2018;(11):4436-4442
Abstract
BACKGROUND Only a small percentage of candidates for bariatric surgery ever undergo a procedure for weight loss. Devices duplicating key effects of bariatric surgeries with removable, fully trans-oral implants could extend their benefits to patients unwilling to undergo anatomy-altering abdominal surgeries. METHODS Thirty-two obese subjects (mean BMI: 42.3) were enrolled in a prospective, multicenter, single-arm, feasibility trial of the first fully trans-oral endoscopic gastrointestinal bypass device. The device is a cuff attached to the distal esophagus by transmural anchors and connected to a 120-cm sleeve diverting undigested nutrients to the jejunum. Bodyweight, vital signs, adverse events, medications, HbA1c, fasting glucose, and lipids were collected at baseline and follow-up visits. Device status was endoscopically assessed every 6 months. RESULTS The fully trans-oral procedure was successful in all subjects without intraoperative adverse events or postoperative infections. Twenty-eight of 32 subjects (88%) remained implanted with continuing follow-up beyond their 12-month visit. At 12 months, the 32 subjects had lost an average of 44.8% of excess body weight, 17.6% of total body weight, 20.8 kg, and 7.5 BMI points. Weight loss depended on capture of ingesta by the esophageal cuff, with 18 of 32 subjects without visible gaps around their cuffs at the 6 month endoscopy having significantly greater EWL (53.6 vs. 33.4% in the remaining subjects, p < 0.002). Mean HbA1c and fasting glucose declined by 1.1% points and 29 mg/dL in type 2 diabetic subjects, 80% of whom had remission of their diabetes at 12 months. CONCLUSION This study demonstrates the feasibility, safety, and efficacy of a fully trans-oral gastrointestinal bypass implant. This purely endoscopic device may provide a valuable addition to the armamentarium of treatment available for the management of morbid obesity.
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Oral copper absorption in men with morbid obesity.
Boullata, J, Muthukumaran, G, Piarulli, A, Labarre, J, Compher, C
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2017;:146-150
Abstract
Copper deficiency has been reported in patients with severe obesity, both before and after bariatric surgery, the latter at increased rates. However, little is known about the absorption of copper. Because of differences in copper dynamics between men and women in the limited available data, we evaluated copper absorption in men who were candidates for bariatric surgery. All patients gave informed consent, approved by the University of Pennsylvania Institutional Review Board, to participate in a pharmacokinetics study. After a 12-h fast, body composition was measured using air displacement plethysmography and a single oral dose of 4mg copper gluconate was given followed by serial measures of serum copper over 10h. Meals and snacks very low in copper were provided. The seven participants had age 52±8years, BMI 44.87±9.01kg/m2 and fat free mass 77.92±14.45kg. Baseline serum copper was 36.1±19.5μg/dL and ceruloplasmin was 50.86±4.58mg/dL. Peak copper absorption occurred within 1-2h. The AUC for six subjects was 254.6±151.3μg/100mLh. The estimated volume of distribution (1.98±0.36L) was ∼25mL/kg fat free mass. In these severely obese men, copper absorption occurred early in spite of their normal copper status, suggesting no impairment of absorption due to obesity. Further studies of copper absorption after the significant weight loss and possible malabsorption derived from bariatric surgery are needed.
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Comparative results of gastric banding in adolescents and young adults.
Hervieux, E, Baud, G, Dabbas, M, Pigeyre, M, Caiazzo, R, Verhaeghe, R, Goulet, O, Aigrain, Y, Révillon, Y, Pattou, F, et al
Journal of pediatric surgery. 2016;(7):1122-5
Abstract
BACKGROUND/PURPOSE Obesity has become a major public health priority. Because of disappointing results obtained with dietary and medical programs, bariatric surgery has been offered to adolescents, although this practice remains controversial. Our aim was to evaluate laparoscopic adjustable gastric banding (LAGB) in adolescents at 2-year follow-up. MATERIAL AND METHODS This prospective study, from 2008 to 2013, compared results between adolescent patients and young adult controls. The LAGB technique and the follow-up program were similar. Weight loss and comorbid disease were analyzed. RESULTS Thirty-six adolescents (mean age at surgery=16.7±1.3years) were operated on and compared to 53 young adults (mean age at surgery=21.7±1.9years). The mean weight and BMI at surgery were 124.4±20.7 and 43.9±5.5kg/m(2), respectively. Among the adolescents, none were diabetic or hypertensive. The mean glycated hemoglobin was 5.6±1.2%. In four cases (11%) dyslipidemia was observed. There was no significant difference between the two groups in terms of initial preoperative weight or BMI. The absolute BMI values at 6, 12 and 24months after surgery were comparable between adolescents and young adults: 38.7 vs 39.8, 36.0 vs 37.6 and 33.5 vs 36.1kg/m(2), respectively. The excess weight loss was higher in adolescents at 12 and 24months: 48.6 vs 37.6% (p=0.03); and 62.3 vs 45.5% (p=0.02). During this period, insulin resistance and dyslipidemia decreased similarly in both groups. CONCLUSION Provided there is careful selection of patients and a supportive multidisciplinary team, satisfying results can be obtained after LAGB in adolescents, comparable to those obtained in young adults at 2-year follow-up.
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Endoluminal Revision (OverStitch (TM) , Apollo Endosurgery) of the Dilated Gastroenterostomy in Patients with Late Dumping Syndrome After Proximal Roux-en-Y Gastric Bypass.
Stier, C, Chiappetta, S
Obesity surgery. 2016;(8):1978-84
Abstract
Dumping syndrome is a long-term postoperative complication of Roux-en-Y gastric bypass procedures. Morphologically, dumping syndrome usually correlates with a dilatation of the gastroenterostomy with accelerated pouch emptying. Conservative therapy includes diet changes, complementary pharmacotherapy and, if symptoms persist, surgical revision. Surgical options include endoscopic, endoluminal surgery to constrict the gastrojejunostomy using a novel endoscopic suturing device (OverStitch(TM), Apollo). In our study, we aimed to assess the viability, safety and efficacy of this procedure in patients with late dumping; 14 patients who had developed late dumping syndrome underwent surgery using an endoscopic suturing technique (OverStitch(TM), Apollo). Late dumping was confirmed by Sigstad score and an oral glucose tolerance test (OGTT). Prior to surgery, objective analysis of pouch emptying speed was assessed by gastric scintigraphy. Surgery was performed under general anaesthesia. None of the 14 patients suffered intra- or postoperative complications. No postsurgical increase in inflammation parameters was observed. The postinterventional pain scale (visual analogue scale) showed a mean score of 0.5 (range 0-10). In 13 of the 14 patients, no dumping was observed 1-month postsurgery. The postoperative Sigstad score (3.07 ± 2.06; range 1-9) showed an impressive reduction compared with the preoperative score (12.71 ± 4.18; range 7-24) (p < 0.001). Postoperative upper gastrointestinal gastrografin swallow revealed regular emptying in all the patients. The endoluminal endoscopic suturing technique-applied here for surgical revision of gastroenterostomy following Roux-en-Y gastric bypass-represents a promising, novel therapeutic option in late dumping syndrome involving minimal trauma and offering rapid reconvalescence.