Distal Small Intestine Research Articles

157 Starch and Dry Matter Digestibility Values Are Not Associated with Improved Growth and Feed Efficiency in Weanling Pigs Fed a Therapeutic Multi-antimicrobial-supplemented Diet

Abstract The porcine terminal small intestinal starch digestive activity and capacity undergo further developmental changes during the acute and adaptive weaning transition. Objective of this study was to address the hypothesis that weanling porcine growth promotion associated with therapeutic antimicrobials was mediated via improving intestinal starch digestion. A total of 170 crossbred barrows (n = 34 pens; 5 barrows/pen), weaned on d 19–21 with an average initial BW of 6.9±0.1 kg, were randomly assigned to two dried whey, corn and SBM-based diets, i.e., control vs. antimicrobials, for 21 d according to a randomized complete block design. The therapeutic multi-antimicrobial diet was supplemented with aureomycin 220, tiamulin 31.2 and ZnO 2,358 at mg/kg diet. The apparent ileal, cecal and total tract digestibility values of total starch and DM were determined by using the titanium dioxide as the digestibility marker (0.30% in the diets). There were no differences (P > 0.05) in the starch digestibility at the ileal (control, 98.3±0.9% vs. antimicrobials, 98.3±0.5%), cecal (control, 96.3±0.6% vs. antimicrobials, 97.1±0.6%) and total tract (control, 98.5±0.3% vs. antimicrobials, 98.7±0.3%) levels between the two diets. Furthermore, there were no differences (P > 0.05) in the DM digestibility at the ileal (control, 75.7±2.2% vs. antimicrobials, 72.7±2.0%), cecal (control, 80.6±1.2% vs. antimicrobials, 81.3±1.2%) and total tract (control, 85.8±0.8% vs. antimicrobials, 84.7±0.9%) levels between the two diets. The Spearman’s correlation analyses revealed no significant associations (P > 0.05) between the growth performance endpoints of ADG, ADFI and F: G and the digestibility values of total starch and DM at the levels of ileal, cecal and total tract. Our results suggest that starch is near complete digestion at the distal small intestine, thus not limiting growth and feed conversion efficiency of weanling pigs fed corn and SBM-based diets. Hence, therapeutic multi-antimicrobial effects are unlikely channeled through modulating digestive utilization efficiency of starch and DM in weanling pigs.

S2972 Primary Squamous Cell Carcinoma of the Ileum - A Rare Entity

Introduction: The small intestine is the most common site for metastatic spread in the gastrointestinal tract. Squamous cell carcinoma (SCC) from a wide variety of sites can metastasize to the small intestine. Primary SCC of the small intestine are rare. We present a rare case of primary SCC of the ileum. Case Description/Methods: A 70-year-old male presented with complaints of abdominal pain for 5 days. Physical exam revealed tenderness on palpation on the right lower quadrant. Labs significant for WBC count of 13k/ul and lactic acid of 10.9 mmol/l. CT Abdomen revealed small bowel obstruction and suspected perforated mass within the ileum. (figure A). Mesenteric lymphadenopathy concerning for metastasis. Laparoscopy revealed an ileal perforation with a matted mass of the distal small intestine which was resected and ileocolonic anastomosis was performed. Gross exam revealed a 6.8*4.7cm ill-defined mass, irregular in appearance with tan pink and nodular texture with areas of necrosis. The mass was submucosal in location, extending to the adjacent mesenteric soft tissue. Histology revealed an invasive poorly differentiated SCC with perforation and invasion of the mesenteric lympho-vascular spaces (figure B). Neoplastic cells were positive for p40(figure C), p63(figure D), ck5/6 and pancytokeratin while negative for ck7, ck20, cdx2, ttf1, synaptophysin, chromogranin, cd45 and S100. The patient had a prolonged postoperative course with multi organ failure, was made palliative on postoperative day 14 and he expired on the same day. Discussion: Several mechanisms have been proposed for primary SCC of the small bowel. Some of which include submucosal squamous epithelium undergoing malignant transformation, aberrant transformation of stem cells into squamous cells with subsequent malignant change. It is difficult to differentiate between primary versus metastatic squamous cell carcinoma of the small bowel. In our patient, imaging studies, immune-histochemical staining and histology results points towards a primary SCC of the ileum. We believe that our patient had primary SCC of the terminal ileum without underlying adenoma, inflammatory disease, or duplication. Optimal treatment and the prognosis are unknown because of the rarity of this condition. Surgery is the mainstay in the management of the disease. Due to the small number of cases available in the literature, the effects of chemotherapy and radiotherapy on the survival and recurrence are unknown.Figure 1.: A CT abdomen axial view showing irregular configuration of a loop of small bowel with adjacent air bubbles suspicious for a perforated mass located within the ileum. B Histology demonstrating tumor nests, composed of large cells with hyperchromatic, pleomorphic nuclei and eosinophilic cytoplasm infiltrating the muscularis propria. Neoplasm is diffusely positive for P40 (C) and p63 (D)-indicating squamous cells

Dietary starch is weight reducing when distally digested in the small intestine

Nowadays, carbohydrate-based foods have a negative consumer connotation and low carb diets have become a popular way to lose weight. Here, we show how digestible starch and flavonoids can be used as a dietary approach to manage food intake and weight gain through elevation of glucagon-like peptide-1 (GLP-1) secretion for gut-brain axis communication. This was achieved by extending the digestion of cooked starch to the distal small intestine using luteolin or quercetin as α-amylase-specific inhibitors with competitive inhibition mechanism. In a mouse model, extended and complete digestion produced a signature blunted glycemic profile that induced elevation of GLP-1 and positive regulation of hypothalamic neuropeptides with significantly reduced food intake and weight gain (p < 0.05). These findings represent a shift in paradigm of dietary carbohydrates from weight increasing to reducing, and have implications for industry and public health related to the design of carbohydrate-based foods/ingredients for managing obesity and diabetes.

Cinnamaldehyde Induces Release of Cholecystokinin and Glucagon-Like Peptide 1 by Interacting with Transient Receptor Potential Ankyrin 1 in a Porcine Ex-Vivo Intestinal Segment Model.

Simple SummaryThe gut is able to “sense” nutrients and release gut hormones to regulate digestive processes. Accordingly, various gastrointestinal cell types possess transient receptor potential channels, cation channels involved in somatosensation, thermoregulation and the sensing of pungent and spicy substances. Recent research shows that both channels are expressed in enteroendocrine cell types responsible for the release of gut peptide hormones such as Cholecystokinin (CCK) and Glucagon-like Peptide-1 (GLP-1). A large array of herbal compounds, used in pig nutrition mostly for their antibacterial and antioxidant properties, are able to activate these channels. Cinnamaldehyde, occurring in the bark of cinnamon trees, acts as an agonist of Transient Receptor Potential Ankyrin 1 (TRPA1)-channel. Capsaicin, the active component of chili peppers, acts as an agonist of Transient Receptor Potential Vanilloid 1 (TRPV1)-channel. This study explored the ability of both compounds to stimulate the release of CCK and GLP-1, and whether this response was mediated by TRP channels, using an ex-vivo intestinal segment model. Results showed mainly the potential of cinnamaldehyde to interact with TRPA1 and trigger CCK and GLP-1 release, while yet being dependent on the location in the small intestine.Cinnamaldehyde and capsaicin have been reported to exert effects on the gastric function, mediated by the interaction with transient receptor potential ankyrin channel 1 (TRPA1) and transient receptor potential vanilloid channel 1 (TRPV1), respectively. This study examined whether these compounds could trigger the release of cholecystokinin (CCK) and/or glucagon-like peptide 1 (GLP-1) in the pig’s gut in a porcine ex-vivo intestinal segment model. Furthermore, it was verified whether this response was mediated by TRPA1 or TRPV1 by using the channel’s antagonist. These gut peptides play a key role in the “intestinal brake”, a feedback mechanism that influences the function of proximal parts of the gut. Structural analogues of cinnamaldehyde were screened as well, to explore structure-dependent activation. Results showed a significant effect of capsaicin on GLP-1 release in the proximal small intestine, TRPV1 independent. TRPA1 showed to be strongly activated by cinnamaldehyde, both in proximal and distal small intestine, evidenced by the release of CCK and GLP-1, respectively. Out of all structural derivates, cinnamaldehyde showed the highest affinity for TRPA1, which elucidates the importance of the α,β-unsaturated aldehyde moiety. In conclusion, cinnamaldehyde as a TRPA1 agonist, is a promising candidate to modulate gastric function, by activating intestinal brake mechanisms.

Psyllium

Psyllium is a natural, predominantly soluble isolated fiber that forms a gel when hydrated. The psyllium gel is not fermented and transits the entire gastrointestinal tract intact. In the small intestine, the psyllium gel increases chyme viscosity, which slows the degradation and absorption of nutrients, which significantly improves fasting blood glucose and hemoglobin A1c levels in individuals with metabolic syndrome and type 2 diabetes mellitus (eg, −37 mg/dL). This delay in nutrient absorption prolongs satiety/delays hunger, leading to decreased energy intake and weight loss in overweight and obese patients. In the distal small intestine (terminal ileum), psyllium becomes more concentrated as water is absorbed, and the highly viscous gel interferes with the active reuptake of bile acids, which are captured in the gel and eliminated via stool. This decrease in the bile acid pool stimulates the liver to produce more bile. As cholesterol is a component of bile, the liver expresses low-density lipoprotein (LDL) cholesterol receptors to harvest LDL-cholesterol from the blood, thereby lowering both LDL-cholesterol (up to 24%) and total cholesterol (up to 20%) levels without affecting high-density lipoprotein cholesterol level. The cholesterol-lowering benefit of psyllium is also additive to the effects of statin drugs, with an effect equivalent to doubling the statin dose. In the large intestine, the nonfermented psyllium gel has a paradoxical “stool normalizing” effect: psyllium softens hard stool in constipation, firms loose/liquid stool in diarrhea, and normalizes stool form/reduces symptoms in irritable bowel syndrome. Psyllium is the only fiber recommended for treatment of constipation and irritable bowel syndrome by the American College of Gastroenterology. Taken together, psyllium is the only fiber supplement that provides 5 of the major health benefits identified by the Food and Drug Administration (cholesterol lowering, improved glycemic control, decreased energy intake/weight loss, decreased blood pressure secondary to weight loss, and laxation/regularity). Psyllium has also been shown clinically to be effective in disease states (eg, hypercholesterolemia, type 2 diabetes, obesity, chronic constipation, chronic diarrhea, hemorrhoids, ulcerative colitis, enteral nutrition–induced diarrhea, fecal incontinence, and irritable bowel syndrome). Taken together, the clinical data support the conclusion that “Fiber needs to gel to keep your patients well.”

Oxygen concentration of gut luminal contents varies post-prandially in growing pigs.

The oxygen (O2 ) concentration of gastrointestinal tract (GIT) contents decreases distally, but little is known about how O2 concentrations are influenced by ingestion of a meal. The O2 concentration in luminal contents at different GIT locations (stomach [cardia and pylorus], proximal, mid- and distal small intestine and caecum) and how these concentrations changed post-prandially were determined. Fifty entire male pigs (22kg bodyweight at the start of study) were fed semi-synthetic diets containing casein, α-lactalbumin, whey protein isolate or zein as the sole source of protein for 8days. A further group of pigs received the casein diet for six days and a semi-synthetic protein-free diet for a further 2days. On day 8, pigs (n=2 per diet and time point) were euthanized post-prandially (0, 1, 2, 4 and 6h), and the stomach, small intestine and caecum were isolated and O2 determined in the GIT contents. Observations at each time point were averaged across the diets (n=10). The mean O2 concentration was markedly higher (p≤0.05) in the stomach compared with the rest of the GIT. The O2 concentration was similar in the small intestinal regions (p>0.05; 1.0%-1.1%) and the caecum (0.9%), apart for the proximal small intestine which had a 24% higher (p≤0.05) O2 concentration than the caecum. The mean O2 concentration in the GIT varied post-prandially (p≤0.05). The O2 concentration in the cardia decreased 1.8%/h over the first two hours post-feeding and thereafter increased 0.3%/h (p≤0.05). In the caecum, the O2 concentration was constant during the first 4h and thereafter increased slightly (p≤0.05). The flow of food through the GIT influenced both the concentration and amount of O2 in GIT luminal contents.

Holdemanella biformis improves glucose tolerance and regulates GLP-1 signaling in obese mice.

Impaired glucose homeostasis in obesity is mitigated by enhancing the glucoregulatory actions of glucagon-like peptide 1 (GLP-1), and thus, strategies that improve GLP-1 sensitivity and secretion have therapeutic potential for the treatment of type 2 diabetes. This study shows that Holdemanella biformis, isolated from the feces of a metabolically healthy volunteer, ameliorates hyperglycemia, improves oral glucose tolerance and restores gluconeogenesis and insulin signaling in the liver of obese mice. These effects were associated with the ability of H. biformis to restore GLP-1 levels, enhancing GLP-1 neural signaling in the proximal and distal small intestine and GLP-1 sensitivity of vagal sensory neurons, and to modify the cecal abundance of unsaturated fatty acids and the bacterial species associated with metabolic health. Our findings overall suggest the potential use of H biformis in the management of type 2 diabetes in obesity to optimize the sensitivity and function of the GLP-1 system, through direct and indirect mechanisms.

261-OR: Transcriptional Profiling of the Intestinal Serotonin System in Individuals with Type 2 Diabetes and Healthy Individuals

Obesity is characterized by increased gut serotonin signaling, which has been shown to enhance hepatic gluconeogenesis favoring hyperglycemia and adipose tissue lipolysis promoting raised levels of free fatty acids and, thus, peripheral insulin resistance. Little is known about the potential involvement of the human gut serotonin system in the pathophysiology of type 2 diabetes. We investigated the transcriptional profile of key enzymes, receptors and transporters in the serotonin system in intestinal biopsies sampled using double-balloon enteroscopy from the duodenum, the jejunum, throughout the remaining small intestine with 30 cm intervals, the ileocecal region, the cecum, the four segments of the colon and the rectum in 12 individuals with type 2 diabetes and 12 gender, age and body mass index-matched healthy controls. Global gene expression analysis was performed on all biopsies, and intestinal expression profiles of genes involved in the serotonin system were mapped and compared between the two groups. We used false discovery rate adjustment to correct for multiple testing. Patients with type 2 diabetes exhibited 2-fold increased mRNA encoding the serotonin-synthesizing enzyme TPH1 in the sigmoid colon (P = 0.027) and the rectum (P &amp;lt; 0.001), and lower levels of mRNA encoding the transporter responsible for reuptake of serotonin in enterocytes, SERT (P = 0.038), and the serotonin-metabolizing enzymes MAOA (P = 0.001) in the distal small intestine and MAOB in the cecum (P = 0.013), the ascending colon (P = 0.020) and the transverse colon (P = 0.011). Our findings provide the first detailed transcriptional profile of key factors in the serotonin system along the entire intestinal tract in humans and lend support to previous animal and human studies suggesting that increased gut serotonin signaling may be involved in the development of dysmetabolic conditions including type 2 diabetes. Disclosure C. Legart: None. C. A. Hagemann: None. A. Ellegaard: None. D. Keating: None. T. Jorsal: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S.

DIARRHEA SYNDROME CAUSED BY CAMPYLOBACTER JEJUNI IN CALVES

ABSTRACT Campylobacter jejuni(C.jejuni) is the leading bacterial cause of food born diarrheal illness and enterocolitis worldwide in human and young animals. A total of 140 samples (100 fecal samples of calves and 40 raw milk samples of cow) were collected from Dakahlia governorate dairy farms for isolation and identification of C.jejuni by using cultural, biochemical, molecular methods and detection of the virulent cadF gene using PCR. Moreover, the isolated C.jejuni subjected for antimicrobial susceptibility test. Then, we develop an experimental infection of rabbits by inoculation with 1 × 109 colony-forming units (cfu) of completely identified C.jejuni. Rabbits divided into 3 groups: infected untreated (G1), infected treated with enrofloxacine (G2), control (G3) to study pathogenesis, fecal inflammatory response, histopthology, immunohistochemistry and ultrastructural changes post inoculation in the three groups. Results revealed that, from 140 fecal and raw milk samples only 41 isolates were bacteriologically and biochemically identified as Campylobacter spp . Seven isolated strains were positively amplified for map A gene specific to C.jejuni and carried the cadF virulence gene. C.jejuniisolateswere resistant to amoxicillin and ampicillin and highly susceptible to norfloxacine and erythromycin.After oral infection with C. jejuni90% of rabbits developed diarrheawith highly fecal inflammatory responses in G1, but mild in G2(treated) and negative in G3(control). Pronounced histopathologic changes were investigated in G1 during the acute phase (days 1 to 3) restricted on distal small intestine and colon including massive destruction of villi and loss of intestinal glands.The submucosa and muscularis mucosa showed the presence of edema with congested blood vessels, while hemorrhage was seen in the muscularispropria layer. The changes were mild and involved only the villi in treated group (G2), while abscent in control (G3). These results were confirmed by immunostaining, suggesting that C.jejuni is capable of invading deep intestinal tissues down to the submucosal layer in G1 while in G2 infection, the reaction was confined mainly to the villi, and was greatly reduced in the submucosa. Electronmicroscope showed all stages of invasion and associating damages from postinfection, colonizationa and villus damage. Thereby, the implementation of hyagenic practices during milking and proper handling of milk during calves feeding with regular monitoring of antibiogram profile are very crucial in preventing C.jejuni infection, colonization and intestinal damage and subsequently economic loss in dairy farm.

Luminal Bioavailability of Orally Administered ω-3 PUFAs in the Distal Small Intestine, and Associated Changes to the Ileal Microbiome, in Humans with a Temporary Ileostomy.

ABSTRACTBackgroundOral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut.ObjectivesWe investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum.MethodsIleostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC–tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing.ResultsThere was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05).ConclusionsOral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy. This study is registered on the ISRCTN registry as ISRCTN14530452.

Diabetes-related intestinal region-specific thickening of ganglionic basement membrane and regionally decreased matrix metalloproteinase 9 expression in myenteric ganglia.

BACKGROUNDThe importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy. Regionally distinct thickening of endothelial basement membrane (BM) of intestinal capillaries supplying the myenteric ganglia coincide with neuronal damage in different intestinal segments. Accelerated synthesis of matrix molecules and reduced degradation of matrix components may also contribute to the imbalance of extracellular matrix dynamics resulting in BM thickening. Among the matrix degrading proteinases, matrix metalloproteinase 9 (MMP9) and its tissue inhibitor (TIMP1) are essential in regulating extracellular matrix remodelling.AIMTo evaluate the intestinal segment-specific effects of diabetes and insulin replacement on ganglionic BM thickness, MMP9 and TIMP1 expression.METHODSTen weeks after the onset of hyperglycaemia gut segments were taken from the duodenum and ileum of streptozotocin-induced diabetic, insulin-treated diabetic and sex- and age-matched control rats. The thickness of BM surrounding myenteric ganglia was measured by electron microscopic morphometry. Whole-mount preparations of myenteric plexus were prepared from the different gut regions for MMP9/TIMP1 double-labelling fluorescent immunohistochemistry. Post-embedding immunogold electron microscopy was applied on ultrathin sections to evaluate the MMP9 and TIMP1 expression in myenteric ganglia and their microenvironment from different gut segments and conditions. The MMP9 and TIMP1 messenger ribonucleic acid (mRNA) level was measured by quantitative polymerase chain reaction.RESULTSTen weeks after the onset of hyperglycaemia, the ganglionic BM was significantly thickened in the diabetic ileum, while it remained intact in the duodenum. The immediate insulin treatment prevented the diabetes-related thickening of the BM surrounding the ileal myenteric ganglia. Quantification of particle density showed an increasing tendency for MMP9 and a decreasing tendency for TIMP1 from the proximal to the distal small intestine under control conditions. In the diabetic ileum, the number of MMP9-indicating gold particles decreased in myenteric ganglia, endothelial cells of capillaries and intestinal smooth muscle cells, however, it remained unchanged in all duodenal compartments. The MMP9/TIMP1 ratio was also decreased in ileal ganglia only. However, a marked segment-specific induction was revealed in MMP9 and TIMP1 at the mRNA levels.CONCLUSIONThese findings support that the regional decrease in MMP9 expression in myenteric ganglia and their microenvironment may contribute to extracellular matrix accumulation, resulting in a region-specific thickening of ganglionic BM.

Effect of Biologically-Relevant Molecules on the Physico-Chemical Properties of Amorphous Magnesium–Calcium Phosphate Nanoparticles

The recently-discovered endogenous formation of amorphous magnesium-calcium phosphate nanoparticles (AMCPs) in human distal small intestine occurs in a complex environment, which is rich in biologically-relevant molecules and macromolecules that can shape the properties and the stability of these inorganic particles. In this work, we selected as case studies four diverse molecules, which have different properties and are representative of intestinal luminal components, namely butyric acid, lactose, gluten and peptidoglycan. We prepared AMCPs in the presence of these four additives and we investigated their effect on the features of the particles in terms of morphology, porosity, chemical nature and incorporation/adsorption. The combined use of electron microscopy, infrared spectroscopy and thermal analysis showed that while the morphology and microstructure of the particles do not depend on the type of additive present during the synthesis, AMCPs are able to incorporate a significant amount of peptidoglycan, similarly to the process in which they are involved in vivo.

The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study.

OBJECTIVERoux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.RESEARCH DESIGN AND METHODSA total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery.RESULTSBoth groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.CONCLUSIONSThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Value of the diving method for capsule endoscopy in the examination of small-intestinal disease: a prospective randomized controlled trial

Video capsule endoscopy (VCE) is limited by poor image quality and incomplete small-bowel transit. This study was designed to evaluate the diving method for VCE in the examination of small-intestinal disease. From July 2017 to September 2017, eligible patients were randomly assigned to 2 groups, the diving group and the control group. For the diving group, 500 mL of water was administered every hour when the capsule reached the small bowel. The primary outcomes were image quality and positive findings. Secondary outcomes were the completion rate of examination, gastric transit time (GTT), small-bowel transit time (SBTT), lesion detection rate, adverse events, and patient satisfaction. One hundred forty patients were included. The scores of endoscopic images in the proximal third andmiddle third of the small bowel in the diving group were significantly higher than that in the control group (3.47 ± .60 vs 3.11 ± .63 [P= .007] and 3.24 ± .59 vs 2.78 ± .74 [P= .002], respectively). The positive findings in the distal third of the small bowel were significantly different between the 2 groups (P= .005). The completion rate in the diving group was significantly higher (92.19% vs 76.32%, respectively; P= .012). The GTT, SBTT, and lesion detection rate were similar in 2 groups (P= .282, .067, and .577, respectively). No discomfort or adverse events were reported except for a few cases of frequent urination. The diving method for VCE examination effectively improves the endoscopic view in the proximal and middle thirds of the small bowel and the positive findings in the distal small intestine and increases the completion rate. (Clinical trial registration number: ChiCTR-RDR-17011823.).

P30: PYY HORMONE UPREGULATES PROXIMAL GLP-1 RELEASE AFTER ROUX EN-Y GASTRIC BYPASS

Abstract Introduction Nowadays Roux-en-Y gastric bypass (RYGB) has provided a powerful treatment for type 2 diabetes mellitus. Nevertheless how anatomical arrangements after RYGB influeces entero-hormonal response and the role of Peptide Tyrosine Tyrosine (PYY) in the restoration of normoglycaemia are still not clear. MATERIAL AND Method We demonstrate that PYY plasma levels showed a remarkable peak, around thirty minutes earlier than GLP-1 or GIP, after mixed-meal administration in non obese Goto – Kakizaki RYGB-operated rats . Also, we found that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Result Histologically the number of GLP-1 positive cells number appeared to increase in the three segments of the small intestine:duodenum jejunum and ileum in GK RYGB-operated rats beyond early presence of nutrient stimulation in the ileum. But nevertheless, PYY positive cell numbers appeared to increased only in the ileum. Conclusion Taking together this findings suggest an earlier central role for PYY in gut hormone regulation after RYGB in our model, contributing to GLP-1 and GIP release and support the existence of enteroendocrine communication routes between the distal and proximal small intestine. Take-home message Enterohormones release changes after bariatric surgery due to the consequences in nutrients flow. The GLP-1 release is increased and we report its related to the PYY regulation.

Neonatal intestinal obstruction: Type I - Septal atresia of distal small intestine

Congenital Intestinal atresia is common cause of neonatal intestinal obstructions. Small intestinal atresia accounts for majority of cases than colonic atresia. In small intestinal atresia Type I is rare form. The plausible etiology is mainly from intra-uterine mesenteric vascular accident and the extent depends on the time and the site of development of obstruction. A 2-day-old baby with history of maternal antenatal scan suspecting of Hirschsprung’s disease presented with clinical signs of lower intestinal obstruction. Barium enema showed features of distal small intestine obstruction for which baby underwent surgery with resection of obstructed segment with end to end anatomises was done. Type I small intestinal atresia was confirmed on histological examination. Thus intestinal obstruction is an emergency encountered in newborn infants requiring early accurate diagnosis by radio imaging modalities and histopathological evaluation. Keywords: Intestinal obstruction, Small intestine atresia, Histopathology.

Effect of a carotenoid-producing Bacillus strain on intestinal barrier integrity and systemic delivery of carotenoids: A randomised trial in animals and humans

The aim of the present study was to investigate effects of the carotenoid-producing Bacillus indicus strain PD01 on intestinal barrier function and its ability to survive passage through the gastrointestinal tract and to assess systemic bioavailability of these carotenoids in vivo. As model for impaired barrier function, 16 early weaned piglets were randomly assigned to a control diet or control diet with PD01 for 23 days. In addition, 67 overweight/obese, otherwise healthy individuals were randomly assigned to groups receiving PD01 or placebo for 6 weeks. PD01 survived passage through the gastrointestinal tract in piglets and human subjects and resulted in significant accumulation of PD01 derived carotenoids (methyl-glycosyl-apo-8′-lycopenoate and glycosyl-apo-8′-lycopene) in human plasma after 3- and 6-weeks supplementation versus baseline (0.044 and 0.076 vs 0 µM, respectively; p < 0.001). PD01 supplementation resulted in higher expression levels of occludin in the distal small intestine (1.38 ± 0.31 vs 0.59 ± 0.14; p = 0.044) and transepithelial electrical resistance in the mid colon (34.1 ± 3.01 vs 24.3 ± 1.13 Ω.cm2; p = 0.019) of early weaned piglets compared to control. In overweight/obese individuals with preserved barrier integrity, PD01 did not affect sugar excretion (p ≥ 0.104). In summary, PD01 survived transit through the gastrointestinal tract, resulted in systemic carotenoid accumulation and improved compromised barrier function outcomes.

The Potentially Modifiable Risk Factor in Idiopathic Intracranial Hypertension: Body Weight.

Idiopathic intracranial hypertension (IIH) prevalence increased in conjunction with rising obesity rates. Here, we highlight the importance of weight management in IIH and introduce glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) as potential treatment strategy for IIH. Weight gain is a risk factor for IIH, and weight loss (via any treatment strategy) plays a key role in IIH management. GLP-1 is an incretin secreted by the distal small intestine in response to a meal. GLP-1 RAs have been shown to improve glycaemic control (no hypoglycaemia) and lower body weight in patients with and without type 2 diabetes. The choroid plexus has been found to express GLP-1 receptors, and treatment with a GLP-1 RA significantly reduces CSF secretion in vitro and intracranial pressure (ICP) in rodents. New research evaluating the pathophysiology of IIH supports GLP-1 RA as a potential treatment for IIH via weight loss dependent and independent mechanism to directly reduce ICP.

An easy and low-cost biomagnetic methodology to study regional gastrointestinal transit in rats.

The identification of gastrointestinal (GI) motility disorders requires the evaluation of regional GI transit, and the development of alternative methodologies in animals has a significant impact on translational approaches. Therefore, the purpose of this study was to validate an easy and low-cost methodology (alternate current biosusceptometry- ACB) for the assessment of regional GI transit in rats through images. Rats were fed a test meal containing magnetic tracer and phenol red, and GI segments (stomach, proximal, medial and distal small intestine, and cecum) were collected to assess tracer's retention at distinct times after ingestion (0, 60, 120, 240, and 360min). Images were obtained by scanning the segments, and phenol red concentration was determined by the sample's absorbance. The temporal retention profile, geometric center, gastric emptying, and cecum arrival were evaluated. The correlation coefficient between methods was 0.802, and the temporal retention of each segment was successfully assessed. GI parameters yielded comparable results between methods, and ACB images presented advantages as the possibility to visualize intrasegmental tracer distribution and the automated scan of the segments. The imaging approach provided a reliable assessment of several parameters simultaneously and may serve as an accurate and sensitive approach for regional GI research in rats.

Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells

Even though metformin is widely used to treat type2 diabetes, reducing glycaemia and body weight, the mechanisms of action are still elusive. Recent studies have identified the gastrointestinal tract as an important site of action. Here we used intestinal organoids to explore the effects of metformin on intestinal cell physiology. Bulk RNA-sequencing analysis identified changes in hexose metabolism pathways, particularly glycolytic genes. Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates. Metformin caused mitochondrial dysfunction and metformin’s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss. Gene expression changes elicited by metformin were replicated in 3D apical-out organoids and distal small intestines of metformin treated mice. We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction. This may explain the effects of metformin on intestinal glucose utilisation and food balance.