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Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum-which is usually described as free of bacteria-became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ-deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.

Exposure of the small intestine to nutrients frequently leads to marked reductions in blood pressure (BP) in type 2 diabetes (T2DM). It remains unclear whether the region of the gut exposed to nutrients influences postprandial cardiovascular responses. To evaluate the cardiovascular responses to proximal and distal small intestinal glucose infusion in health and T2DM. Double-blind, randomized, crossover design. Single center in Australia. 10 healthy subjects and 10 T2DM patients. Volunteers were studied on 2 occasions, when a transnasal catheter was positioned with infusion ports opening 13 cm and 190 cm beyond the pylorus. A 30-g bolus of glucose was infused into either site and 0.9% saline into the alternate site over 60 minutes. BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow were measured over 180 minutes. Systolic BP was unchanged in response to both infusions in health, but decreased in T2DM, with a greater reduction after proximal versus distal infusion (all P ≤ .01). The increment in HR did not differ between treatments in health, but was greater after distal versus proximal infusion in T2DM (P = .02). The increases in SMA blood flow were initially greater, but less sustained, with proximal versus distal infusion in health (P < .001), a pattern less evident in T2DM. In T2DM, postprandial hypotension may be mitigated by diversion of nutrients from the proximal to the distal small intestine.

BACKGROUND: Protein infusion in the small intestine results in intestinal brake activation: a negative feedback mechanism that may be mediated by the release of gastrointestinal peptides resulting in a reduction in food intake. It has been proposed that duodenum, jejunum and ileum may respond differently to infused proteins. OBJECTIVE: To investigate differences in ad libitum food intake, feelings of hunger and satiety and the systemic levels of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucose and insulin after intraduodenal, intrajejunal and intraileal protein infusion. METHODS: Fourteen subjects (four male, mean age: 23±2.1 years, mean body mass index: 21.6±1.8 kg m −2 ) were intubated with a naso-ileal catheter in this double-blind, randomized, placebo-controlled crossover study. Test days (four in total, executed on consecutive days) started with the ingestion of a standardized breakfast, followed by the infusion of 15 g of protein in the duodenum, jejunum or ileum over a period of 60 min. Food intake was measured by offering an ad libitum meal and Visual Analogue Scale (VAS) scores were used to assess feelings of hunger and satiety. Blood samples were drawn at regular intervals for CCK, GLP-1, PYY, glucose and insulin analyses. RESULTS: Intraileal protein infusion decreased ad libitum food intake compared with both intraduodenal and placebo infusion (ileum: 628.5±63 kcal vs duodenum: 733.6±50 kcal, P <0.01 and placebo: 712.2±53 kcal, P <0.05). GLP-1 concentrations were increased after ileal infusion compared with jejunal and placebo infusion, whereas CCK concentrations were only increased after intraileal protein infusion compared with placebo. None of the treatments affected VAS scores for hunger and satiety nor plasma concentrations of PYY and glucose. CONCLUSIONS: Protein infusion into the ileum decreases food intake during the next meal compared with intraduodenal infusion, whereas it increases systemic levels of GLP-1 compared with protein infusion into the jejunum and placebo respectively.

The site of intestinal fat delivery affects satiety and may affect food intake in humans. Animal data suggest that the length of the small intestine exposed to fat is also relevant. The aim of the present study was to investigate whether increasing the areas of intestinal fat exposure and the way it is exposed would affect satiety parameters and food intake. In the present single-blind, randomised, cross-over study, fifteen volunteers, each intubated with a naso-ileal tube, received four treatments on consecutive days. The oral control (control treatment) was a liquid meal (LM) containing 6 g fat ingested at t = 0 min, with saline infusion at t = 30–120 min. Experimental treatments were a fat-free LM at t = 0 min, with either 6 g oil delivered sequentially (2 g duodenal, t = 30–60 min; 2 g jejunal, t = 60–90 min; 2 g ileal, t = 90–120 min), simultaneously (2 g each to all sites, t = 30–120 min) or ileal only (6 g ileal, t = 30–120 min). Satiety parameters (hunger and fullness) and cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) secretion were measured until t = 180 min, when ad libitum food intake was assessed. Only the ileum treatment reduced food intake significantly over the control treatment. The ileum and simultaneous treatments significantly reduced hunger compared with the control treatment. Compared with control, no differences were observed for PYY, CCK and GLP-1 with regard to 180 min integrated secretion. Ileal fat infusion had the most pronounced effect on food intake and satiety. Increasing the areas of intestinal fat exposure only affected hunger when fat was delivered simultaneously, not sequentially, to the exposed areas. These results demonstrate that ileal brake activation offers an interesting target for the regulation of ingestive behaviour.

The aim of this prospective study was to compare the intraindividual aperistaltic effect of 40 mg hyoscine N -butylbromide (HBB/Buscopan) with that of 1 mg glucagon on small bowel motility by using magnetic resonance imaging (MRI). Ten healthy volunteers underwent two separate 1.5-T MRI studies (HBB/glucagon) after a standardized oral preparation with an aqueous solution of Gd-DOTA and ispaghula (Metamucil). A 2D T1-w GRE sequence was acquired (TR 2.7 ms/TE 1.3 ms, temporal resolution 0.25 s) before and after intravenous (i.v.) drug administration and motility was followed over 1 h. On the resulting images the cross-sectional luminal diameters were assessed and plotted over time. Baseline motility frequency, onset of aperistalsis, duration of arrest, reappearance of motility and return to normal motility were analysed. Significant differences regarding reliability and duration of aperistalsis were observed. In the HBB group aperistalsis lasted a mean of 6.8 ± 5.3 min compared with 18.3 ± 7 min after glucagon ( p  < 0.0001). In 50% of cases HBB did not accomplish aperistalsis, whereas glucagon always succeeded ( p  = 0.05). There were no significant differences in terms of baseline and end frequencies for the onset of aperistalsis (22.2 ± 37.5 s HBB/13.4 ± 9.2 s glucagon, p  = 0.1), nor for the return to normal motility. Arrest of small bowel motion is achieved more reliably and lasts significantly longer after i.v. administration of 1 mg glucagon compared with 40 mg HBB.

Purpose The transit of dosage forms through the small intestine is considered to be constant at around 3 h, and unaffected by the presence of food. Here we address this assumption and examine how the timing of tablet and food administration can influence small intestine transit time. Methods A non-disintegrating, radiolabelled tablet was given to ten healthy volunteers in a three-way crossover study using three different feeding regimens (1) fasted (tablet administered on an empty stomach and food withheld for four hours) (2) fed (tablet administered after food) and (3) pre-feed (tablet administered 45 min before food). Tablet transit through the gastrointestinal tract was followed using gamma scintigraphy. Results The small intestinal transit times of tablets after fasted and fed dosing regimens were similar, median 204 and 210 min respectively. With the pre-feed dose, small intestinal transit time was significantly shorter than in the fasted or fed state at 141 min. With this dosing regimen, in six of the volunteers tablets were in the upper small intestine when food arrived and these had a median small intestinal transit time of 100 min. Conclusions The timing of food ingestion has a clear effect on small intestinal transit of single-unit formulations and this has implications for drug bioavailability.

During summer days the extreme heat may cause damage to the integrity of animal intestinal barrier. Little information is available concerning morphological changes in the duck intestines in response to high temperature. And the molecular mechanisms underlying the pathogenesis of high temperature-induced intestinal injury remain undefined. MicroRNAs (miRNAs) are known to play key roles in post-transcriptional regulation of gene expression that influences various biological processes. The purpose of this study was to explore the changes in morphology and miRNA expression profiles of the three intestinal segments (duodenum, jejunum and ileum) of ducks in response to high temperature. Sixty female Shaoxing ducks (Anas platyrhynchos), 60 days old, were allocated in two groups, including control ducks kept at 25 °C, and ducks subjected to high ambient temperatures of 30–40 °C for 15 successive days, which mimicked the diurnal temperature variations experienced in hot seasons. Three ducks from each group were executed at the end of feeding experiment, and the samples of three intestinal segments were collected for morphological examination and Illumina deep sequencing analyses. Histopathological examination of the intestinal mucous membrane was performed with HE staining method. The results demonstrated that varying degrees of damage to each intestinal segment were found in heat-treated ducks, and there were more severe injuries in duodenum and jejunum than those in ileum. Illumina high-throughput sequencing and bioinformatic methods were employed in this study to identify the miRNA expression profile of three different intestinal tissues in control and heat-treated ducks. A total of 75,981,636, 88,345,563 and 100,179,422 raw reads were obtained from duodenum, jejunum and ileum, respectively, from which 74,797,633 clean reads in duodenal libraries, 86,406,445 clean reads in jejunal libraries, and 98,518,858 lean reads in ileal libraries were derived after quality control, respectively. And a total of 276 known and 182 novel miRNAs were identified in the three intestinal segments of ducks under control and heat-treated conditions. By comparing the same tissues in different conditions, 16, 18 and 15 miRNAs were found to be significantly differentially expressed between control and heat-treated ducks in duodenum, jejunum and ileum, respectively, of which 1 miRNA was expressed in both the duodenum and jejunum, 2 miRNAs were expressed in both the duodenum and ileum, and 3 miRNAs were found to be expressed in both the jejunum and ileum. In addition, two differentially expressed miRNAs in each comparison were randomly selected and validated by quantitative qRT-PCR. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the differentially expressed miRNAs may be involved in the high temperature-induced intestinal injury in ducks. Our work provides the comprehensive miRNA expression profiles of small intestines in the normal and heat-treated ducks. These findings suggest the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the high temperature-induced changes in the duck small intestine.

It is generally believed that cells in the gut transduce sensory information through the paracrine action of hormones. Kaelberer et al. found that, in addition to the well-described classical paracrine transduction, enteroendocrine cells also form fast, excitatory synapses with vagal afferents (see the Perspective by Hoffman and Lumpkin). This more direct circuit for gut-brain signaling uses glutamate as a neurotransmitter. Thus, sensory cues that stimulate the gut could potentially be manipulated to influence specific brain functions and behavior, including those linked to food choices. Science , this issue p. eaat5236 ; see also p. 1203 A neuroepithelial circuit that connects the intestinal lumen to the brain stem in one synapse has been identified. The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell—the enteroendocrine cell. However, these electrically excitable cells contain several features of epithelial transducers. Using a mouse model, we found that enteroendocrine cells synapse with vagal neurons to transduce gut luminal signals in milliseconds by using glutamate as a neurotransmitter. These synaptically connected enteroendocrine cells are referred to henceforth as neuropod cells. The neuroepithelial circuit they form connects the intestinal lumen to the brainstem in one synapse, opening a physical conduit for the brain to sense gut stimuli with the temporal precision and topographical resolution of a synapse.

Background This study aimed to investigate the tolerability and impact of milk of magnesia (MoM) on interfraction rectal filling during prostate cancer radiotherapy. Methods Two groups were retrospectively identified, each consisting of 40 patients with prostate cancer treated with radiotherapy to prostate+/-seminal vesicles, with daily image-guidance in 78Gy/39fractions/8 weeks. The first-group followed anti-flatulence diet with MoM started 3-days prior to planning-CT and continued during radiotherapy, while the second-group followed the same anti-flatulence diet only. The rectum between upper and lower limit of the clinical target volume (CTV) was delineated on planning-CT and on weekly cone-beam-CT (CBCT). Rectal filling was assessed by measurement of anterio-posterior diameter of the rectum at the superior and mid levels of CTV, rectal volume (RV), and average cross-sectional rectal area (CSA; RV/length). Results Overall 720 images (80 planning-CT and 640 CBCT images) from 80 patients were analyzed. Using linear mixed models, and after adjusting for baseline values at the time of planning-CT to test the differences in rectal dimensions between both groups over the 8-week treatment period, there were no significant differences in RV ( p  = 0.4), CSA ( p  = 0.5), anterio-posterior diameter of rectum at superior ( p  = 0.4) or mid level of CTV ( p  = 0.4). In the non-MoM group; 22.5% of patients had diarrhea compared to 60% in the MoM group, while 40% discontinued use of MoM by end of radiotherapy. Conclusion The addition of MoM to antiflatulence diet did not reduce the interfraction variation in rectal filling but caused diarrhea in a substantial proportion of patients who then discontinued its use.

Paneth cells were first described in the late 19th century by Gustav Schwalbe and Josef Paneth as columnar epithelial cells possessing prominent eosinophilic granules in their cytoplasm. Decades later there is continued interest in Paneth cells as they play an integral role in maintaining intestinal homeostasis and modulating the physiology of the small intestine and its associated microbial flora. Paneth cells are highly specialized secretory epithelial cells located in the small intestinal crypts of Lieberkühn. The dense granules produced by Paneth cells contain an abundance of antimicrobial peptides and immunomodulating proteins that function to regulate the composition of the intestinal flora. This in turn plays a significant role in secondary regulation of the host microvasculature, the normal injury and repair mechanisms of the intestinal epithelial layer, and the levels of intestinal inflammation. These critical functions may have even more importance in the immature intestine of premature infants. While Paneth cells begin to develop in the middle of human gestation, they do not become immune competent or reach their adult density until closer to term gestation. This leaves preterm infants deficient in normal Paneth cell biology during the greatest window of susceptibility to develop intestinal pathology such as necrotizing enterocolitis (NEC). As 10% of infants worldwide are currently born prematurely, there is a significant population of infants contending with an inadequate cohort of Paneth cells. Infants who have developed NEC have decreased Paneth cell numbers compared to age-matched controls, and ablation of murine Paneth cells results in a NEC-like phenotype suggesting again that Paneth cell function is critical to homeostasis to the immature intestine. This review will provide an up to date and comprehensive look at Paneth cell ontogeny, the impact Paneth cells have on the host-microbial axis in the immature intestine, and the repercussions of Paneth cell dysfunction or loss on injury and repair mechanisms in the immature gut.