Gut Diameter Research Articles

GutMap: A New Interface for Analysing Regional Motility Patterns in ex vivo Mouse Gastrointestinal Preparations.

Different regions of the gastrointestinal tract have specific functions and thus distinct motility patterns. Motility is primarily regulated by the enteric nervous system (ENS), an intrinsic network of neurons located within the gut wall. Under physiological conditions, the ENS is influenced by the central nervous system (CNS). However, by using ex vivo organ bath experiments, ENS regulation of gut motility can also be studied in the absence of CNS influences. The current technique enables the characterisation of small intestinal, caecal, and colonic motility patterns using an ex vivo organ bath and video imaging protocol. This approach is combined with the novel edge detection script GutMap, available in MATLAB, that functions across Windows and Mac platforms. Dissected intestinal segments are cannulated in an organ bath containing physiological saline with a camera mounted overhead. Video recordings of gut contractions are then converted to spatiotemporal heatmaps and analysed using the GutMap software interface. Using data analysed from the heatmaps, parameters of contractile patterns (including contraction propagation frequency and velocity as well as gut diameter) at baseline and in the presence of drugs/treatments/genetic mutations can be compared. Here, we studied motility patterns of female mice at baseline and in the presence of a nitric oxide synthase inhibitor (Nω-Nitro-L-arginine; NOLA) (nitric oxide being the main inhibitory neurotransmitter of gut motility) to showcase the application of GutMap. This technique is suitable for application to a broad range of animal models of clinical disorders to understand underlying biological pathways contributing to gastrointestinal dysfunction. Key features • Enhanced video imaging analysis of gut contractility in rodents using a novel software interface. • New edge detection algorithm to accurately contour curvatures of the gastrointestinal tract. • Allows for output of high-resolution spatiotemporal heatmaps across Windows and Mac platforms. • Edge detection and analysis method makes motility measurements accessible in different gut regions including the caecum and stomach.

The development of zebrafish pancreas affected by deficiency of Hedgehog signaling

The pancreas development depends on complex regulation of several signaling pathways, including the Hedgehog (Hh) signaling via a receptor complex component, Smoothened, which deficiency blocks the Hh signaling. Such a defect in birds and mammals results in an annular pancreas. We showed that in developing zebrafish, the mutation of Smoothened or inhibition of Hh signaling by its antagonist cyclopamine caused developmental defects of internal organs, liver, pancreas, and gut. In particular, the pancreatic primordium was duplicated. The two exocrine pancreatic primordia surround the gut. This phenomenon correlates with a significant reduction of the gut's diameter, causing the annular pancreas phenotype.

Catch-up growth in intrauterine growth-restricted piglets associated with the restore of pancreatic and intestinal functions via porcine glucagon-like peptide-2 microspheres

ABSTRACT Intrauterine growth restriction (IUGR) results in abnormal morphology and gastrointestinal function, such as reduced villi height and crypt depth, thinner mucosa and muscle layers, and reduced brush border enzyme activities, delayed gastric emptying, increased stress response. As a gastrointestinal growth factor, the manner by which the porcine glucagon-like peptide-2 (pGLP-2) microsphere administration restored the gastrointestinal function and growth performance of IUGR piglets was investigated. Fourteen newborn Duroc × (Yorkshire × Landrace) IUGR piglets (0.92 ± 0.113 kg) were assigned into the IUGR (negative control group) and pGLP-2 microsphere groups. The piglets in group pGLP-2 were intraperitoneally administered with 100 mg pGLP-2 microspheres on day 1 after birth. From days 15 to 26 of trial, the body weight of the pGLP-2 group was significantly higher than that of the control. IUGR piglets of group pGLP-2 showed a significantly increased pancreas weight, serum insulin content and activity of lipase and amylase. Injection of pGLP-2 microspheres restored the intestinal absorptive capacity by significantly increasing the mRNA expression of the sodium-glucose cotransporter 1 in the jejunum and the peptide transporter 1 in the jejunum. It also restored the redox balance by increasing the catalase mRNA expression and decreasing the heat shock protein 70 mRNA expression. In addition, this improvement was associated with the significant increase in gut diameter, length and weight. Therefore, it was concluded that the injection of pGLP-2 microspheres was a suitable therapeutic strategy for compensatory growth in low birth weight IUGR piglets.

Gross intestinal morphometry and allometry in ruminants.

While some descriptions of ruminants' dietary adaptations suggest that the length of the intestinal tract reflects the proportion of grass or browse in the diet, this assumption has been questioned. We collated data on body mass (BM), as well as small intestine, caecum, colon/rectum, large and total intestine length in 68 ruminant species, and, while accounting for the phylogenetic structure of the dataset, evaluated both allometric scaling and the potential influence of diet, digestive physiology or climate proxies on measures of intestine length. Intestinal length generally scaled to BM at an exponent higher than the 0.33 expected due to geometry. Diet or digestive physiology proxies did not have an influence on any intestinal length measures, though some proxies indicating more arid natural habitats were positively correlated with measures of the large intestine. The relative size of a forestomach compartment, the omasum, was negatively correlated with intestine length. The results indicate that intestine length measures provide little indication of feeding type or digestive physiology, but rather indicate adaptations to aridity. Higher-than-geometry scaling of intestinal length may be related to the necessity of maintaining geometric (or metabolic) scaling of intestinal surface area while keeping gut diameter, and hence the diffusion distances, small. The way in which space trade-offs determine the macroanatomy of different organs in the abdominal cavity, such as the omasum and the intestine, deserves further investigation.

Discriminating movements of liquid and gas in the rabbit colon with impedance manometry.

High-resolution impedance manometry is a technique that is well established in esophageal motility studies for relating motor patterns to bolus flow. The use of this technique in the colon has not been established. In isolated segments of rabbit proximal colon, we recorded motor patterns and the movement of liquid or gas boluses with a high-resolution impedance manometry catheter. These detected movements were compared to video recorded changes in gut diameter. Using the characteristic shapes of the admittance (inverse of impedance) and pressure signals associated with gas or liquid flow we developed a computational algorithm for the automated detection of these events. Propagating contractions detected by video were also recorded by manometry and impedance. Neither pressure nor admittance signals alone could distinguish between liquid and gas transit, however the precise relationship between admittance and pressure signals during bolus flow could. Training our computational algorithm upon these characteristic shapes yielded a detection accuracy of 87.7% when compared to gas or liquid bolus events detected by manual analysis. Characterizing the relationship between both admittance and pressure recorded with high-resolution impedance manometry can not only help in detecting luminal transit in real time, but also distinguishes between liquid and gaseous content. This technique holds promise for determining the propulsive nature of human colonic motor patterns.

Modelling side to side intestinal anastomosis.

Side-to-side intestinal anastomosis is a surgical procedure where an incision is performed between two parallel segments of gut and then they are sutured together. The purpose of this paper is to investigate if the standard surgical practice diameter used in anastomosis leads to undesirable closed circulatory flows which may be harmful to the gut tissue. A finite element model for the chyme flow in a side by side anastomosis with realistic user configurable parameters is developed and solved in a wide range of situations. We analyze the flow crossing the anastomosis, the normalized pressure difference in the gut section and the streamlines that show the presence or absence of closed flow regions for a set of surgically feasible anastomosis diameter values. In contrast with the findings of simpler analytical models, closed flows do not appear in any of these cases. The study shows that the current standard surgical practice where the anastomosis diameter is similar to the gut diameter does not lead to undesirable effects predicted by some simple analytical models.

Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice

The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central nervous system. Changes in ENS function are a major cause of GI symptoms and disease and may contribute to GI symptoms reported in neuropsychiatric disorders including autism. It is well established that isolated colon segments generate spontaneous, rhythmic contractions known as Colonic Migrating Motor Complexes (CMMCs). A procedure to analyze the enteric neural regulation of CMMCs in ex vivo preparations of mouse colon is described. The colon is dissected from the animal and flushed to remove fecal content prior to being cannulated in an organ bath. Data is acquired via a video camera positioned above the organ bath and converted to high-resolution spatiotemporal maps via an in-house software package. Using this technique, baseline contractile patterns and pharmacological effects on ENS function in colon segments can be compared over 3-4 hr. In addition, propagation length and speed of CMMCs can be recorded as well as changes in gut diameter and contraction frequency. This technique is useful for characterizing gastrointestinal motility patterns in transgenic mouse models (and in other species including rat and guinea pig). In this way, pharmacologically induced changes in CMMCs are recorded in wild type mice and in the Neuroligin-3R451C mouse model of autism. Furthermore, this technique can be applied to other regions of the GI tract including the duodenum, jejunum and ileum and at different developmental ages in mice.

Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice.

The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central nervous system. Changes in ENS function are a major cause of GI symptoms and disease and may contribute to GI symptoms reported in neuropsychiatric disorders including autism. It is well established that isolated colon segments generate spontaneous, rhythmic contractions known as Colonic Migrating Motor Complexes (CMMCs). A procedure to analyze the enteric neural regulation of CMMCs in ex vivo preparations of mouse colon is described. The colon is dissected from the animal and flushed to remove fecal content prior to being cannulated in an organ bath. Data is acquired via a video camera positioned above the organ bath and converted to high-resolution spatiotemporal maps via an in-house software package. Using this technique, baseline contractile patterns and pharmacological effects on ENS function in colon segments can be compared over 3-4 hr. In addition, propagation length and speed of CMMCs can be recorded as well as changes in gut diameter and contraction frequency. This technique is useful for characterizing gastrointestinal motility patterns in transgenic mouse models (and in other species including rat and guinea pig). In this way, pharmacologically induced changes in CMMCs are recorded in wild type mice and in the Neuroligin-3(R451C) mouse model of autism. Furthermore, this technique can be applied to other regions of the GI tract including the duodenum, jejunum and ileum and at different developmental ages in mice.

Effects ofSaccharomyces cerevisiaeorboulardiiyeasts on acute stress induced intestinal dysmotility

AIMTo investigate the capacity of Saccharomyces cerevisiae (S. cerevisiae) and Saccharomyces boulardii (S. boulardii) yeasts to reverse or to treat acute stress-related intestinal dysmotility.METHODSAdult Swiss Webster mice were stressed for 1 h in a wire-mesh restraint to induce symptoms of intestinal dysmotility and were subsequently killed by cervical dislocation. Jejunal and colon tissue were excised and placed within a tissue perfusion bath in which S. cerevisiae, S. boulardii, or their supernatants were administered into the lumen. Video recordings of contractility and gut diameter changes were converted to spatiotemporal maps and the velocity, frequency, and amplitude of propagating contractile clusters (PCC) were measured. Motility pre- and post-treatment was compared between stressed animals and unstressed controls.RESULTSS. boulardii and S. cerevisiae helped to mediate the effects of stress on the small and large intestine. Restraint stress reduced jejunal transit velocity (mm/s) from 2.635 ± 0.316 to 1.644 ± 0.238, P < 0.001 and jejunal transit frequency (Hz) from 0.032 ± 0.008 to 0.016 ± 0.005, P < 0.001. Restraint stress increased colonic transit velocity (mm/s) from 0.864 ± 0.183 to 1.432 ± 0.329, P < 0.001 and frequency to a lesser degree. Luminal application of S. boulardii helped to restore jejunal and colonic velocity towards the unstressed controls; 1.833 ± 0.688 to 2.627 ± 0.664, P < 0.001 and 1.516 ± 0.263 to 1.036 ± 0.21, P < 0.001, respectively. S. cerevisiae also had therapeutic effects on the stressed gut, but was most apparent in the jejunum. S. cerevisiae increased PCC velocity in the stressed jejunum from 1.763 ± 0.397 to 2.017 ± 0.48, P = 0.0031 and PCC frequency from 0.016 ± 0.009 to 0.027 ± 0.007, P < 0.001. S. cerevisiae decreased colon PCC velocity from 1.647 ± 0.187 to 1.038 ± 0.222, P < 0.001. Addition of S. boulardii or S. cerevisiae supernatants also helped to restore motility to unstressed values in similar capacity.CONCLUSIONThere is a potential therapeutic role for S. cerevisiae and S. boulardii yeasts and their supernatants in the treatment of acute stress-related gut dysmotility.

Neural mechanisms of peristalsis in the isolated rabbit distal colon: a neuromechanical loop hypothesis.

Propulsive contractions of circular muscle are largely responsible for the movements of content along the digestive tract. Mechanical and electrophysiological recordings of isolated colonic circular muscle have demonstrated that localized distension activates ascending and descending interneuronal pathways, evoking contraction orally and relaxation anally. These polarized enteric reflex pathways can theoretically be sequentially activated by the mechanical stimulation of the advancing contents. Here, we test the hypothesis that initiation and propagation of peristaltic contractions involves a neuromechanical loop; that is an initial gut distension activates local and oral reflex contraction and anal reflex relaxation, the subsequent movement of content then acts as new mechanical stimulus triggering sequentially reflex contractions/relaxations at each point of the gut resulting in a propulsive peristaltic contraction. In fluid filled isolated rabbit distal colon, we combined spatiotemporal mapping of gut diameter and intraluminal pressure with a new analytical method, allowing us to identify when and where active (neurally-driven) contraction or relaxation occurs. Our data indicate that gut dilation is associated with propagating peristaltic contractions, and that the associated level of dilation is greater than that preceding non-propagating contractions (2.7 ± 1.4 mm vs. 1.6 ± 1.2 mm; P < 0.0001). These propagating contractions lead to the formation of boluses that are propelled by oral active neurally driven contractions. The propelled boluses also activate neurally driven anal relaxations, in a diameter dependent manner. These data support the hypothesis that neural peristalsis is the consequence of the activation of a functional loop involving mechanical dilation which activates polarized enteric circuits. These produce propulsion of the bolus which activates further anally, polarized enteric circuits by distension, thus closing the neuromechanical loop.

Inference of mechanical states of intestinal motor activity using hidden Markov models

BackgroundContractions and relaxations of the muscle layers within the digestive tract alter the external diameter and the internal pressures. These changes in diameter and pressure move digesting food and waste products. Defining these complex relationships is a fundamental step for neurogastroenterologists to be able define normal and abnormal gut motility.ResultsUtilising an in vitro technique that allows for the simultaneous recording of intraluminal pressure (manometry) and gut diameter (video) in an isolated section of rabbit colon, we developed a technique to help define the mechanical states of the muscle at any point in space and time during actual peristaltic movements. This was achieved by directly relating the changes in pressure to the changes in diameter along the length of the gut studied. For each individual measure of pressure or diameter, 3 dynamic state components were identified; increasing or decreasing changes or a stable period. Two additional static state components, fully contracted and fully distended, were defined for the diameter. Then qualitative mechanical states of the muscle activity were defined as combinations of these state components. A hidden Markov model was used to correlate adjacent-in-time samples, and the Viterbi algorithm was used to infer the most likely sequence of mechanical states based on the observed data. From this a spatiotemporal map of the mechanical states was produced, showing the regions of active contractions, active relaxations, or passive states along the length of the gut throughout the entire recording period.ConclusionsThe identification of mechanical muscles states based on gut diameter and intraluminal pressure was possible by modelling muscle activation with a hidden Markov model.

Hypertrophy of intestinal smooth muscle in cats

Pathological findings of four cats with severe and diffuse smooth muscle hypertrophy of the small intestine (MHSI) are reported and compared to those of five cats with segmental MHSI secondary to neoplastic obstruction and four controls. Histology demonstrated a constant association between idiopathic MHSI and submucosal fibrosis and chronic lymphoplasmacytic enteritis. Morphometry (gut diameter, thickness and area of muscular layers, number and density of smooth muscle nuclei) and MIB-1-immunolabelling showed that the thickness increase was mostly due to hypertrophy, but hyperplasia was also evident. Microbiology from ileal content samples was performed in two cats with primary MHSI, and Campylobacter spp. were isolated, which were also demonstrated by immunohistochemistry and ultrastructure. The association of chronic enteritis with idiopathic MHSI suggests that factors released in intestinal inflammation may also act as hypertrophy stimuli for smooth muscle cells.

Morphological adaptations of the digestive tract of tropical cyprinids and cichlids to diet

Eight cyprinids with four different feeding habits fall into two distinct groups according to morphological adaptations of the intestine: (i) carnivorous and omnivorous cyprinids with large gut diameter and large mucosal surface which decreases from the foregut to the hindgut; (ii) benthivorous and phytoplanktivorous cyprinids with small gut diameter and small mucosal surface which is more or less uniformly built along the intestine, although relative gut length may vary considerably (1.45–6.10). Although the intestine of phytoplanktivorous cyprinids is extremely elongated, it appears less adapted for processing a refractory diet than that of cichlids with similar feeding habits.

The ability of an elemental diet to support nutrition and adaptation in the short gut syndrome.

85% enterectomy or jejunal biopsy was randomly carried out on 80 male Sprague-Dawley rats, 300-350 gm. After recovery, rats in each group were randomly fed either elemental diet (ED) or rat chow. All rats were sacrificed 8 weeks postoperatively. Biopsied rats gained more weight with ED than chow (22% vs. 18%; p less than .01). Resection produced greater weight loss than biopsy (p less than .01) and slower gain (p less than .01). The failure to gain was most marked in ED rats, significantly less than in the chow group (p less than .05) by week two. A fall in hemoglobin, protein and albumin was seen: neither the fall nor difference between the groups was significant (p greater than .05). Enterectomized chow rats ate 22% more than their controls (p greater than .05). Increase in bowel length after resection, equally divided between jejunum and ileum, was 21% with ED and 26% with chow. Gut diameter after resection increased 104% and 98% with chow and ED, respectively. Villus height increased 65% in the jejunum of both enterectomized groups and 85% and 78% with chow and ED, respectively, in the ileum. Changes in gut length, diameter and villus height are significant in each group (p less than .01) but not between groups (p greater than .05).

Effects of oxytetracycline and oleandomycin. Separately and together in pig diets

1. Normal rations containing oleandomycin (2·5 g./ton), oxytetracycline (10 g./ton) and oleandomycin (2·5 g./ton)plus oxytetracycline (10 g./ton) were given to females and castrates which had previously received creep feed with or without oxytetracycline.2. Forty-eight pigs were individually fed on the rations from 50 to 200 lb. live-weight, a restricted scale of intake based on live-weight being adopted.3. Pigs receiving the mixed supplement and those given oxytetracycline alone grew significantly faster and utilised their feed more efficiently than those given oleandomycin alone. Differences between the mixed supplement group and those receiving oxytetracycline were not significant.4. Treatment with antibiotic, either in the creep feed or after weaning, had no effect on carcass measurements. Females had less depth of fat at the shoulder, mid-back and loin compared with castrates and the carcasses were significantly longer.5. Visceral weights were not influenced by antibiotic treatment but pigs supplemented with oleandomycin had a shorter gut than those receiving a combination of antibiotics. There was a significant reduction in gut weight n i pigs which had received unsupplemented creep feed but no consistent effect on the thickness of the intestine wall or gut diameter. Females had significantly heavier kidneys and spleens than castrates.