Explore the vast range of titles available.

Background This study investigated the role of proximal small intestinal bypass (PSIB) and distal small intestinal bypass (DSIB) as well as their long-term effects on weight loss and glucose metabolism in high-sugar and high-fat diet-induced obese rats. Methods Sprague-Dawley rats were divided into four groups: PSIB, bypassing 60% of the proximal small intestine length; DSIB, bypassing 60% of the distal small intestine length; sham-operated (Sham) animals; and control animals. All rats were fed a high-sugar and high-fat diet after surgery. The primary outcome measures were body weight, food intake, fasting blood glucose (FBG) levels, oral glucose tolerance test (OGTT), and the insulin tolerance test (ITT). Results Global body weight (BW) and food intake in the PSIB and DSIB groups were lower than those in the Sham group at postoperative week 2. BW and food intake in the PSIB group were lower than those in the DSIB group at postoperative week 24. The PSIB and DSIB groups exhibited improvement in glucose tolerance at postoperative weeks 4, 8, and 24. The PSIB and DSIB groups exhibited improvement in FBG at postoperative week 24, and only the DSIB group exhibited improvement in insulin sensitivity. Conclusions This study provides experimental evidence that PSIB surgery induced a better and more persistent weight loss effect than DSIB surgery and that the two types of intestinal bypass surgeries yielded equivalent and stable long-term improvement in glucose tolerance in an obese rat model.

BackgroundIntestinal ischemia-reperfusion during cardiac surgery with cardiopulmonary bypass (CPB) may trigger bacterial translocation and contribute to the development of sepsis. In this study, we aimed to investigate the intricate relationship between gut microbial dysbiosis and sepsis after cardiac surgery with CPB.MethodsThis prospective observational case-control study followed 60 patients who underwent cardiac surgery with CPB, with 54 fecal samples collected one day before surgery and 33 samples within 24–72 hours after surgery. Metagenomic sequencing was performed to analyze the gut microbiome. Patients with postoperative sepsis were identified according to the third international consensus (Sepsis-3).ResultsTwo dysbiotic enterotypes were identified in all gut microbial samples (IDDF2023-ABS-0139 Figure 1. Two enterotypes identified in all samples. (A) JSD-based PCoA plot at the genus level. (B) Shannon diversity. (C) The variation of the four enterotype-driven genera). Enterotype I exhibited higher alpha diversity (p=2.7×10–5) and was driven by Citrobacter and Fusicatenibacter, while enterotype II was driven by Cronobacter and Pluralibacter. In addition, an abundance of Citrobacter and Cronobacter were positively correlated (p<0.05) with the APACHE II score and ICU days. Patients who underwent cardiac surgery with CPB tended to switch their enterotypes to enterotype II (IDDF2023-ABS-0139 Figure 2. Enterotype-dependent microbial response. (A) Enterotype switch after cardiac surgery with CPB. (B) Linear regression), with the proportion of samples in enterotype II rising from 31.5% to 63.6% (p=6.7×10–3). Moreover, 17 patients developed postoperative sepsis, and most of them had their postoperative samples (n=11) presenting enterotype II. Furthermore, enterotype-dependent microbial alterations were found in these 17 patients, with the depletion of Cronobacter (p=3.2×10–4) and Pluralibacter (p=0.014) primarily occurring in patients with postoperative enterotype II.ConclusionsThis study highlights the possibility of two different postoperative enterotypes following cardiac surgery with CPB, each with a distinct microbiome profile and response pattern. We recommend that an enterotype-aware clinical intervention should be conducted during the entire cardiac surgery with CPB to reduce the risk of postoperative sepsis.Abstract IDDF2023-ABS-0139 Figure 1Two enterotypes identified in all samples (A) JSD-based PCoA plot at the genus level (B) Shannon diversity (C) The variation of the four enterotype-driven generaAbstract IDDF2023-ABS-0139 Figure 2Enterotype-dependent microbial response (A) Enterotype switch after cardiac surgery with CPB (B) Linear regression

Background/PurposeMalignant small bowel obstruction (mSBO) is a common consequence of advanced malignancies. Surgical consultation is common, however data on the outcomes following an operation are lacking. We investigated a specific operative approach—intestinal bypass—to determine the outcomes associated with this intervention.MethodsPatients with a preoperative diagnosis of mSBO who underwent intestinal bypass between 2015 and 2021 were included. Isolated colonic obstruction was excluded as was gastric outlet obstruction. Perioperative and postoperative outcomes were measured, including complications, overall survival, return to oral intake, and return to intended oncologic therapy. Patients were additionally grouped as to whether the operation was performed as elective or as inpatient.ResultsOverall, 55 patients were identified, with a mean age of 61.2 ± 14 years. The most common primary malignancy was colorectal cancer (65.5%) and 80% of patients had a preoperative diagnosis of metastatic disease. Small bowel to colon was the most common bypass procedure (51%). Severe complications occurred in 25.5% of patients with three in-hospital mortalities (5.5%). Survival rates at 30, 90, and 180 days were 91%, 80%, and 62%, respectively. The majority of patients were discharged to home (85.5%) and were tolerating an oral diet (74.6%). Twenty-seven patients (49.1%) returned to some form of oncologic treatment. ConclusionsPatients with mSBO face a potentially terminal condition. In this study, approximately 75% of patients who underwent intestinal bypass were able to regain the ability to eat, and 49% returned to oncologic therapy. Although retrospective, these data suggest the approach is efficacious for palliation of this difficult sequela of advanced cancer.

Background/objectivesBile acids (BA) act as detergents in intestinal fat absorption and as modulators of metabolic processes via activation of receptors such as FXR and TGR5. Elevated plasma BA as well as increased intestinal BA signalling to promote GLP-1 release have been implicated in beneficial health effects of Roux-en-Y gastric bypass surgery (RYGB). Whether BA also contribute to the postprandial hypoglycaemia that is frequently observed post-RYGB is unknown.MethodsPlasma BA, fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), GLP-1, insulin and glucose levels were determined during 3.5 h mixed-meal tolerance tests (MMTT) in subjects after RYGB, either with (RYGB, n = 11) or without a functioning gallbladder due to cholecystectomy (RYGB-CC, n = 11). Basal values were compared to those of age, BMI and sex-matched obese controls without RYGB (n = 22).ResultsFasting BA as well as FGF19 levels were elevated in RYGB and RYGB-CC subjects compared to non-bariatric controls, without significant differences between RYGB and RYGB-CC. Postprandial hypoglycaemia was observed in 8/11 RYGB-CC and only in 3/11 RYGB. Subjects who developed hypoglycaemia showed higher postprandial BA levels coinciding with augmented GLP-1 and insulin responses during the MMTT. The nadir of plasma glucose concentrations after meals showed a negative relationship with postprandial BA peaks. Plasma C4 was lower during MMTT in subjects experiencing hypoglycaemia, indicating lower hepatic BA synthesis. Computer simulations revealed that altered intestinal transit underlies the occurrence of exaggerated postprandial BA responses in hypoglycaemic subjects.ConclusionAltered BA kinetics upon ingestion of a meal, as frequently observed in RYGB-CC subjects, appear to contribute to postprandial hypoglycaemia by stimulating intestinal GLP-1 release.

After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1). To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut. Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark. Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes. Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB. The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry. Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon. Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

Nanometric biocompatible Metal-Organic Frameworks (nanoMOFs) are promising candidates for drug delivery. Up to now, most studies have targeted the intravenous route, related to pain and severe complications; whereas nanoMOFs for oral administration, a commonly used non-invasive and simpler route, remains however unexplored. We propose here the biofriendly preparation of a suitable oral nanocarrier based on the benchmarked biocompatible mesoporous iron(III) trimesate nanoparticles coated with the bioadhesive polysaccharide chitosan (CS). This method does not hamper the textural/structural properties and the sorption/release abilities of the nanoMOFs upon surface engineering. The interaction between the CS and the nanoparticles has been characterized through a combination of high resolution soft X-ray absorption and computing simulation, while the positive impact of the coating on the colloidal and chemical stability under oral simulated conditions is here demonstrated. Finally, the intestinal barrier bypass capability and biocompatibility of CS-coated nanoMOF have been assessed in vitro , leading to an increased intestinal permeability with respect to the non-coated material, maintaining an optimal biocompatibility. In conclusion, the preservation of the interesting physicochemical features of the CS-coated nanoMOF and their adapted colloidal stability and progressive biodegradation, together with their improved intestinal barrier bypass, make these nanoparticles a promising oral nanocarrier.

Lymphatic vessels are crucial for fluid absorption and the transport of peripheral immune cells to lymph nodes. However, in the small intestine, the lymphatic fluid is rich in diet-derived lipids incorporated into chylomicrons and gut-specific immune cells. Thus, intestinal lymphatic vessels have evolved to handle these unique cargoes and are critical for systemic dietary lipid delivery and metabolism. This Review covers mechanisms of lipid absorption from epithelial cells to the lymphatics as well as unique features of the gut microenvironment that affect these functions. Moreover, we discuss details of the intestinal lymphatics in gut immune cell trafficking and insights into the role of inter-organ communication. Lastly, we highlight the particularities of fat absorption that can be harnessed for efficient lipid-soluble drug distribution for novel therapies, including the ability of chylomicron-associated drugs to bypass first-pass liver metabolism for systemic delivery. In all, this Review will help to promote an understanding of intestinal lymphatic–systemic interactions to guide future research directions. Lymphatic vessels are important for fluid absorption and immune cell transport. This Review discusses the role of the intestinal lymphatic system in transport and inter-organ communication, exploring lipid absorption mechanisms, gut microenvironment influences, immune cell trafficking and intestinal lymphatics as a drug delivery system. Key points Lipid absorption is critical for life and requires an orchestrated, multicellular response between intestinal villus epithelial cells, extracellular matrix and lymphatic vessels for packaging and transporting fat. Lipid droplets in enterocytes are potentially important for gut lipid absorption and transport. Lymphatic vessels dynamically regulate lipid transport through various signalling mechanisms and control of cell–cell junctions. Gastrointestinal and sex hormones are active regulators of fat absorption and gut lymphatic transport. Mechanistic knowledge of lipid absorption can be leveraged for the discovery of novel drug delivery vehicles and anti-obesity treatments. Understanding gut lymphatic system interactions with the microbiome is essential for health and disease.

ContextLaparoscopic sleeve gastrectomy (LSG), now the most commonly performed bariatric operation, is a highly effective treatment for obesity. While Roux-en-Y gastric bypass is known to impair intestinal fractional calcium absorption (FCA) and negatively affect bone metabolism, LSG's effects on calcium homeostasis and bone health have not been well characterized. ObjectiveWe determined the effect of LSG on FCA, while maintaining robust 25-hydroxyvitamin D (25OHD) levels and recommended calcium intake. Design, setting, participantsProspective pre-post observational cohort study of 35 women and men with severe obesity undergoing LSG. Main outcomesFCA was measured preoperatively and 6 months postoperatively with a gold-standard dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and bone mineral density (BMD) by dual-energy X-ray absorptiometry and quantitative computed tomography. ResultsMean ± SD FCA decreased from 31.4 ± 15.4% preoperatively to 16.1 ± 12.3% postoperatively (P < 0.01), while median (interquartile range) 25OHD levels were 39 (32-46) ng/mL and 36 (30-46) ng/mL, respectively. Concurrently, median 1,25-dihydroxyvitamin D level increased from 60 (50-82) pg/mL to 86 (72-107) pg/mL (P < 0.01), without significant changes in parathyroid hormone or 24-hour urinary calcium levels. Bone turnover marker levels increased substantially, and areal BMD decreased at the proximal femur. Those with lower postoperative FCA had greater areal BMD loss at the total hip (ρ = 0.45, P < 0.01). ConclusionsFCA decreases after LSG, with a concurrent rise in bone turnover marker levels and decline in BMD, despite robust 25OHD levels and with recommended calcium intake. Decline in FCA could contribute to negative skeletal effects following LSG.

Roux-en-Y Gastric Bypass may be associated with an alteration of protein bioavailability in relation to intestinal remodeling. Our study aimed to test this hypothesis by Roux-en-Y Gastric Bypass. Diet-induced obese rats underwent Roux-en-Y Gastric Bypass surgery (RYGB rats) while a Sham-operated control group was used. All rats received a 15 N-labeled protein meal 1 or 3 months after surgery and were euthanized 6h later. Protein digestibility, 15 N recovered in organs and urea pool, fractional protein synthesis rate, and intestinal morphometry were assessed. Protein digestibility was similar in all groups (94.2±0.3%). The small intestine was hypertrophied in RYGB rats 1 month after surgery, weighing 9.1±0.2g vs. 7.0±0.3g in Sham rats (P = 0.003). Villus height and crypt depth were increased in the alimentary limb and ileum of RYGB rats. However, Roux-en-Y Gastric Bypass had no impact on the fractional synthesis rate. In the gastrointestinal tract, 15 N retention only differed in the ileal mucosa and was higher in RYGB rats at 1 month (0.48±0.2% vs. 0.3±0.09%, P = 0.03). 15 N recovery from the liver, muscle, and skin was lower in RYGB rats at 1 month. 15 N recovery from urinary and plasma urea was higher in RYGB rats at both times, resulting in increased total deamination (13.2±0.9% vs. 10.1±0.5%, P<0.01). This study showed that Roux-en-Y Gastric Bypass did not affect protein digestibility. Dietary nitrogen sequestration was transitorily and moderately diminished in several organs. This was associated with a sustained elevation of postprandial deamination after Roux-en-Y Gastric Bypass, whose mechanisms merit further studies.