Mucosal surface area of a reversed intestinal segment in rats.

Only scarce knowledge exists of morphologic changes after antiperistaltic reversal of the small intestine. Previous animal models using a reversed segment of the small intestine after massive intestinal resection have been mostly concerned with assessing absorption. A rat model was therefore developed for the purpose of studying mucosal surface area in the small intestine after reversal of an intestinal segment. A reversal of 10 cm, representing a length of about 10%, was found suitable for the investigation. Marked dilatation of the reversed segment occurred. A pronounced increase in mucosal surface area caused by mucosal hyperplasia was observed. The mucosal surface area in an anastomosed, but not reversed, segment also increased markedly compared with a group undergoing no operation, although less than in the reversed segment. We conclude that a reversed intestinal segment will increase mucosal surface area in an optimal length used for this purpose. This increase is possibly caused by prolonged exposure to intestinal chyme.     

Mucosal Surface Area of a Reversed Intestinal Segment in Rats

Only scarce knowledge exists of morphologic changes after antiperistaltic reversal of the small intestine. Previous animal models using a reversed segment of the small intestine after massive intestinal resection have been mostly concerned with assessing absorption. A rat model was therefore developed for the purpose of studying mucosal surface area in the small intestine after reversal of an intestinal segment. A reversal of 10 cm, representing a length of about 10%, was found suitable for the investigation. Marked dilatation of the reversed segment occurred. A pronounced increase in mucosal surface area caused by mucosal hyperplasia was observed. The mucosal surface area in an anastomosed, but not reversed, segment also increased markedly compared with a group undergoing no operation, although less than in the reversed segment. We conclude that a reversed intestinal segment will increase mucosal surface area in an optimal length used for this purpose. This increase is possibly caused by prolonged exposure to intestinal chyme.     

Morphological and functional adaptation of the small intestine after colectomy and ileal pouch-anal anastomosis in rats

BACKGROUND AND AIMS: This study investigated morphological and functional changes in the small bowel after colectomy and ileal pouch-anal anastomosis (IPAA). METHODS AND MATERIALS: In 15 rats electrolyte, glucose, and water absorption was determined by in vivo single-pass perfusion of the proximal and distal small intestine 15 weeks after IPAA. Afterwards the small intestine was resected for morphometric evaluation. Controls were 15 identically treated rats without operation. RESULTS: IPAA led to a significant increase in the small intestinal diameter and a significant increase in villus length and density, which was more apparent in ileum than in jejunum. Therefore the mucosal surface per unit serosa increased significantly by 59% in the jejunum and by 76% in the ileum. In the pouch there was a significant increase in goblet cell density, crypt depth, and diameter of the muscularis which was not detectable in the segments proximal from the pouch. Due to the increase in mucosal surface there was a significant increase in total glucose and electrolyte and sorption in the ileum while absorption rates per unit mucosa were unchanged, with the exception of an increase in mucosal sodium absorption. Jejunal absorption and ileal absorption of water remained unchanged. CONCLUSION: Adaptation of the small intestine after IPAA leads to colonic metaplasia in the pouch and intestinal hyperplasia proximal from the pouch. The loss of colonic absorption is compensated by the increase in ileal mucosal surface with subsequently elevated electrolyte and glucose absorption. Changes in intestinal permeability may be responsible for additional water depletion, which is compensated by the upregulation of enteric water and sodium absorption.     

Effect of different total parenteral nutrition fuel mixes on small intestinal growth and differentiation in the infant miniature pig

Insulin has been proposed as an important factor in the regulation of growth and differentiation of the small intestine. In the newborn miniature pig, we induced significant physiologic increases in serum insulin and the insulin/glucagon ratio without altering serum glucose, beta-hydroxybutyrate, glucagon, cortisol, T3, and T4 using glucose-based total parenteral nutrition (TPN) in one group (group G) compared with a combination of glucose and fat in another group (group G/F). Control animals were sham-operated and fed a pelleted diet (group OC). Duodenal villus surface area and mucosal height were significantly greater in group G/F compared with group G. No other differences between the TPN groups were found in small intestinal growth, mucosal protein, deoxyribonucleic acid and ribonucleic acid content, and disaccharidase activities. As anticipated, group OC demonstrated increased intestinal length, weight, and villous surface area compared with the TPN groups. Ileal sucrase and jejunal and ileal maltase activities were greater in the TPN groups compared with those in group OC. Physiologic changes in serum insulin and the insulin/glucagon ratio induced by the TPN fuel mix do not appear to have altered small intestinal growth, composition, and differentiation in the healthy small intestine.     

Effect of dietary fat on the distribution of mucosal mass and cell proliferation along the small intestine.

This study investigated how substitution of long chain triglycerides for glucose in a mixed diet affects the overall small intestinal mucosal mass and the distribution of mucosal mass and cell proliferation along the small intestine. Four groups of eight female Wistar rats (180-200 g) were isocalorically fed mixed diets containing the essential fatty acid rich oil Efamol substituted for glucose at concentrations of 1.2%, 10%, 25%, and 50% total calories for 20 to 23 days. The small intestine was divided into three equal length segments and whole gut weights, mucosal weights, protein and DNA determined. Cell proliferation was estimated from the two hour accumulation of vincristine arrested metaphases in microdissected crypts at points 0%, 17%, 33%, 50%, 66%, and 100% small intestinal length. There were no differences between groups in parameters of overall small intestinal or distal segment mucosal mass. With increasing levels of fat, however, there was a significant trend for the mucosal mass of the proximal segment to fall and that of the middle segment to rise. The pattern of two hour metaphase accumulation reflected these changes. These regional changes in mucosal mass and cell proliferation may reflect differences in the sites of absorption of fat and glucose.     

Cholesterol synthesis and high density lipoprotein uptake are regulated independently in rat small intestinal epithelium.

The rates of high density lipoprotein HDL uptake and cholesterol synthesis were compared in the normocholesterolaemic (SW) and genetically hypercholesterolaemic (RICO) rat intestine. The RICO rat has a hyperintestinal cholesterol synthesis. 14C sucrose, a marker which becomes irreversibly entrapped within the cells, was used to measure total rat HDL uptake over 24 hours in the various cells of the small intestinal mucosa. The rates of sterol synthesis were estimated in vivo with 1-14C acetate, as previously validated. The rates of HDL uptake in the upper villus cells were similar along the length of the small intestine in both types of rat, but the rates of sterol synthesis varied up to eightfold. When the mucosal epithelium was divided along the villus/crypt axis, HDL uptake increased two to threefold and cholesterol synthesis two to fivefold in the upper villus compared with the crypt cells in both SW and RICO rats. The high cholesterogenesis in the mucosal cells of the RICO rat is not related to a modified HDL cholesterol uptake. Thus, cholesterol synthesis and HDL uptake seem to be regulated independently in the rat small intestinal mucosa.     

Morphometric and Biomechanical Intestinal Remodeling Induced by Fasting in Rats

The function of the small intestine is mechanical to a large degree. To understand the function it is necessary to know how the mechanical stresses and strains can be computed. Nutrition plays an important role in the maintenance of normal gut structure and function. The small intestine undergoes functional changes when food is withheld. To explore the morphological and biomechanical remodeling during starvation, intestinal segments from the fed and fasted rat duodenum, jejunum, and ileum were investigated. After seven days of fasting the animals lost 22% of the body weight and the intestinal mass per length decreased by nearly 40% in the duodenum. Fasting decreased the plasma levels of glucose, insulin, triglyceride, and cholesterol whereas the level of free fatty acids increased (P < 0.001). Fasting decreased the outer circumferential length, wall thickness, wall area, inner circumferential length, and luminal area at the three locations (P < 0.001). Histological examination showed that the mucosal and the submucosal thickness decreased during fasting (P < 0.001), whereas the muscle layers were unchanged. The residual strain on the mucosal surface was compressive. The serosal residual strain was tensile and increased with the highest values after four days of fasting in the duodenum and jejunum (P < 0.001). Fasting shifted the stress–strain curves to the right in both circumferential and longitudinal directions at the three locations (P < 0.04). In conclusion pronounced biomechanical and structural remodeling occurred in the small intestine during fasting for up to one week. Since the contractile properties depend on the passive properties (according to the well-known Hill's model), it can be predicted that the smooth muscle contractile function will also change.     

Small intestinal morphology in experimental diabetic rats: a stereological study on the effects of an aldose reductase inhibitor (ponalrestat) given with or without conventional insulin therapy

Summary The gross and microscopical dimensions of small intestines from 12-week old streptozotocin-diabetic rats receiving no therapeutic intervention were compared with those from animals receiving insulin alone or in conjunction with the aldose reductase inhibitor, ponalrestat. Four regions along each intestine were analysed stereologically. Insulin had significant beneficial effects on body weight as well as on intestinal length, width, surface area and volume. In contrast, ponalrestat did not improve body weight deficits and was associated with crypt hypertrophy and a reduced villous surface/crypt volume ratio. There were interaction effects between insulin and ponalrestat for intestinal length and primary mucosal surface area. All groups displayed significant regional differences in surface area of primary mucosa and volume of muscularis externa. Only untreated diabetic rats failed to reveal regional variation in the surface area and volume of villi. Ratios of villous surface area/crypt volume varied from region-to-region in insulin-treated diabetic rats but not in other groups. The study fails to reveal any beneficial effect of aldose reductase inhibition on the changes in intestinal morphology seen in experimental diabetes.     

非甾体抗炎药对小肠黏膜的损伤作用

研究显示非甾体抗炎药（NSAIDs）不仅可引起胃十二指肠黏膜损伤，还可引起小肠黏膜损伤。目的：探讨NSAIDs引起小肠黏膜损伤的发病机制及其病理生理变化。方法：50只大鼠随机分为空白对照组和四组模型组，以不同NSAID灌胃14d。另20只大鼠先分别行胆管结扎和假手术。再予吲哚美辛灌胃。观察各组大鼠一般情况和小肠黏膜大体、组织病理学改变，测定小肠组织髓过氧化物酶（MPO）、丙二醛（MDA）、超氧化物歧化酶（SOD）、一氧化氮（NO）含量。结果：四种NSAID均能造成大鼠小肠黏膜损伤，吲哚美辛、布洛芬和塞来昔布组累计损伤深度和面积显著高于空白对照组（P〈0．05），其中以吲哚美辛组损伤最重，阿司匹林组则与空白对照组无明显差异。各模型组小肠组织MPO含量均显著高于空白对照组，SOD活性则显著低于空白对照组（P〈0．05），MDA和NO含量均呈上升趋势，但分别仅吲哚美辛组和布洛芬组与空白对照组相比有显著差异（P〈0．05）。假手术组小肠黏膜损伤显著重于空白对照组（P〈0．05），胆管结扎组与空白对照组相比无明显差异。结论：NSAIDs可通过炎症反应、氧自由基损伤、NO过度产生以及药物的肝肠循环损害小肠上皮屏障，破坏小肠结构的完整性。     

Insulin-like growth factor-I stimulates Na+-dependent glutamine absorption in piglet enterocytes

Agents that enhance intestinal glutamine transport may be useful under conditions in which intestinal mucosal function is compromised. Here we examined whether oral administration of insulin-like growth factor (IGF-I) stimulates absorption of l-glutamine in piglet intestine. Colostrum-deprived piglets received human recombinant IGF-I (3.5 mg/kg/day) or vehicle orogastrically every 8 hr for four days after birth. Piglets were killed on day 5 and the proximal jejunum was removed. Basal electrical parameters and l-glutamine-stimulated changes in short-circuit current were measured in muscle-stripped tissues, and rates of l-glutamine uptake were measured in everted jejunal sleeves. Oral IGF-I had no effect on jejunal mucosal mass. Short-circuit current responses to mucosal addition of 10 mM l-glutamine were increased by oral IGF-I. Total and carrier-mediated uptakes of l-glutamine per milligram were greater in tissues from IGF-I-treated piglets due to a significantly greater maximal rate of uptake (J _max). Thus, oral administration of IGF-I stimulates Na⁺-dependent glutamine absorption in piglet small intestine, an effect that is independent of changes in intestinal mucosal mass.     

Advances in Small Bowel Imaging

The small intestine has been difficult to examine by traditional endoscopic and radiologic techniques. Within the past 10 years, advances have led to an explosion of technologies that facilitate examination of the entire small intestine. Wireless video capsule endoscopy, deep enteroscopy using balloon-assisted or spiral techniques, computer tomography (CT) and magnetic resonance (MR) enterography have facilitated the diagnosis, monitoring, and management of patients with small intestinal diseases. These technologies are complementary, each with its advantages and limitations. Capsule endoscopy provides a detailed view of the mucosal surface and has excellent patient acceptance, but does not allow therapeutics. Deep enteroscopy allows careful inspection of the mucosa and therapeutics, but is time consuming and invasive. Enterography (CT or MR) allows examination of the small bowel wall and surrounding structures. The initial best test for detecting small intestinal disease depends on clinical presentation and an astute differential diagnosis.     

Hypertrophy of the small intestine after its partial resection in the rat

The authors investigated the ultrastructure of small intestinal epithelium in the rat, 3 weeks after resection of the proximal half of the small intestine. They sought to determine: (1) whether the compensatory hypertrophy of the mucosa of the residual small intestine results in changes in the microvilli, in addition to prolongation of the villi; and, (2) whether it is possible to provide evidence of less complete morphologic differentiation in the more rapidly migrating enterocytes. The epithelium on the surface of villi in animals after resection does not differ ultrastructurally from controls and is formed by completely differentiated cellular elements. It is apparent that the compensatory enlargement of the intestinal absorption surface is a result of the hypertrophy of the mucosal villi, and not of changes in the microvilli.     

Quantitation of the histological changes found in small intestinal biopsy specimens from children with suspected coeliac disease

The histological appearances in 85 peroral small intestinal biopsies from children have been analysed quantitatively by the method of Dunnill and Whitehead (1972). As applied to such biopsy specimens, this technique provides indices of both the mucosal volume and of the mucosal surface-to-volume ratio.When compared with controls, ;flat' biopsies from children with untreated coeliac disease invariably showed much smaller surface-to-volume (c:lh) ratios. The mucosal volumes (h) of these biopsies were, however, significantly increased. Specimens showing less marked abnormalities (socalled ;partial villous atrophy') had c:lh ratios in an intermediate range, but, like the biopsies from untreated coeliacs, h values were significantly increased.In morphologically normal biopsies correlation of surface-to-volume ratios with age showed that c:lh ratios were significantly smaller in younger children. Some of these lower c:lh ratios overlapped the range observed in abnormal biopsies showing partial villous atrophy. However, in the atrophic biopsies additional histological changes, such as abnormalities of the surface epithelial cells and an increased inflammatory cell infiltration of the lamina propria, were invariably present. Slight changes in biopsies from children under 2 years of age should, therefore, be interpreted cautiously, and should not necessarily be regarded as pathological on the evidence of the villous pattern alone.The quantitative technique employed proved reproducible under normal working conditions, and its greatest practical value would appear to be in following accurately serial changes in biopsies from the same patient.     

Pathogenic importance of intestinal hypermotility in NSAID-induced small intestinal damage in rats

BACKGROUND/AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin produce damage in the small intestine as a major adverse reaction. We examined the effect of various NSAIDs on intestinal motility and investigated the pathogenic importance of motility changes in the intestinal ulcerogenic response to indomethacin in rats. METHODS: Animals without fasting were given various NSAIDs (indomethacin 10 mg/kg, diclofenac 40 mg/kg, flurbiprofen 20 mg/kg, naproxen 40 mg/kg) s.c., and in the case of indomethacin, the following parameters were examined in the small intestine 24 h later; the lesion score, the number of enterobacteria and myeloperoxidase (MPO) as well as inducible nitric oxide (iNOS) activity. Intestinal motility was monitored as intraluminal pressure recordings using a balloon under anesthesia. RESULTS: All NSAIDs tested decreased mucosal PGE(2) levels and produced hemorrhagic lesions in the small intestine, accompanied by intestinal hypermotility. As representative of NSAIDs, indomethacin also increased the extent of enterobacterial invasion and MPO as well as iNOS activity before the occurrence of intestinal damage, and the hypermotility response was observed earlier than the onset of any other event caused by this agent. The intestinal lesions induced by indomethacin were prevented by either supplementation with dmPGE(2), inhibition of bacterial invasion with ampicillin or inhibition of iNOS activity with aminoguanidine, while the hypermotility response was prevented by dmPGE(2) only. In addition, the observed effects of dmPGE(2) were all mimicked by atropine when the intestinal hypermotility was suppressed by this agent. CONCLUSION: These results suggest the pathogenic importance of intestinal hypermotility in the intestinal ulcerogenic response to NSAIDs in rats and show that this event is critical for the occurrence of enterobacterial invasion under PG deficiency, followed by various inflammatory changes and damage in the mucosa. This study also suggests that the antispasmodic drug is protective against NSAID-induced intestinal lesions.     

Phytohemagglutinin-induced diarrheal disease

A purified plant lectin, phytohemagglutinin (PHA), or crude red kidney bean (RKB) from which it was derived, when incorporated as 1% of dietary protein into a purified casein protein diet caused weanling rats to fail to grow or lose weight in comparison to control animals pair fed an isonitrogenous, isocaloric diet. Feeding PHA was observed to cause diarrhea: fecal wet and dry weights were increased within 2 days after starting the diet. Increased fecal weight was caused by increased dry weight as well as by an increased fecal water content. On reversion to a normal casein diet, rapid amelioration of the antinutritional effects of PHA occurred with resumption of normal growth rate. Specific binding of PHA to the microvillus region of the small intestinal epithelium was demonstrated using rabbit anti-PHA and fluorescein-labeled goat anti-rabbit immunoglobulin. PHA binding was observed after chronic intake in the diet or when applied to normal tissuein vitro. Loss of PHA binding to the intestine was observed to occur within 48 hr on reversion to a control casein diet. No significant morphological damage to the microvilli or the mucosal villus architecture was observed to accompany PHA adherence under these experimental conditions. Antinutritional and antiabsorptive effects of dietary PHA were associated with diarrhea. PHA adhered to the microvillus membrane of the small intestinal villus surface during the diarrheal state. After cessation of dietary PHA intake, weight gain and growth was accompanied by loss of PHA adherence to the small bowel mucosal surface. Adherence of PHA to the intestinal mucosal surface was an important cause of the nutritional and malabsorptive changes observed.This research was supported in part by grant AM 31093 from the National Institutes of Health.     

Significant changes in intestinal lymphatic system and immune response elicited by Peyer's patch excision in adult rats

Abstract The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP-excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP-excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP-excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen-specific immune response was further studied in PP-excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen-specific antibody in the intestinal mucosa using anti-CT antibody and those of cells secreting anti-CT Ig in the intestinal lymph by enzyme-linked immunospot (ELISPOT) assay showed a significant reduction of CT-specific antibody production in PP-excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses.     

Hyperenteroglucagonaemia and small intestinal mucosal growth after colonic perfusion of glucose in rats.

Beside intraluminal factors, humoral agents play an important role in intestinal adaptation. Enteroglucagon, the mucosal concentration of which is maximal in the terminal ileum and colon, is the strongest candidate for the role of small intestinal mucosal growth factor. The present experiment was designed to study the role of colonic enteroglucagon in stimulating mucosal growth in rats with a normal small intestine. After eight days of glucose large bowel perfusion, enteroglucagon plasma concentrations were 120.7 +/- SEM 9.2 pmol/l, versus 60.1 +/- 6.8 in mannitol perfused control rats (p less than 0.001). Gastrin, cholecystokinin, neurotensin, pancreatic glucagon, and insulin plasma concentrations were unchanged. Crypt cell proliferation, measured by the vincristine metaphase arrest technique, increased significantly in the small intestine of glucose perfused animals (p less than 0.005-0.001) in comparison with the controls. This resulted in a greater mucosal mass in both proximal and distal small bowel: mucosal wet weight, DNA, protein and alpha D-glucosidase per unit length intestine were all significantly higher (p less than 0.05-0.001) than in mannitol perfused rats. Our data, therefore, support the hypothesis that enteroglucagon is an enterotrophic factor and stress the possible role of the colon in the regulation of small bowel trophicity.     

Mucosal pathobiology and molecular signature of epithelial barrier dysfunction in the small intestine in irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal disorders in developed countries. Its etiology remains unknown; however, a common finding, regardless of IBS subtype, is the presence of altered intestinal barrier. In fact, signaling and location of cell‐to‐cell adhesion proteins, in connection with increased immune activity, seem abnormal in the intestinal epithelium of IBS patients. Despite that most research is performed on distal segments of the intestine, altered permeability has been reported in both, the small and the large bowel of all IBS subtypes. The small intestine carries out digestion and nutrient absorption and is also the site where the majority of immune responses to luminal antigens takes place. In fact, the upper intestine is more exposed to environmental antigens than the colon and is also a site of symptom generation. Recent studies have revealed small intestinal structural alterations of the epithelial barrier and mucosal immune activation in association with intestinal dysfunction, suggesting the commitment of the intestine as a whole in the pathogenesis of IBS. This review summarizes the most recent findings on mucosal barrier alterations and its relationship to symptoms arising from the small intestine in IBS, including epithelial structural abnormalities, mucosal immune activation, and microbial dysbiosis, further supporting the hypothesis of an organic origin of IBS.     

Does the fatty acid profile of dietary fat influence its trophic effect on the small intestinal mucosa?

To compare the enterotrophic effects of different triglycerides, five groups of eight rats were fed mixed diets giving 50% of calories as oils rich in either essential fatty acids (EFA), alpha-linolenic acid, fully saturated fatty acids, oleic acid, or medium chain fatty acids. After 21-24 days there were no significant differences between the groups in overall small intestinal whole gut weight, mucosal weight, or mucosal DNA; overall mucosal protein showed slight variation (p < 0.05) that was compatible with differences in food intake between the groups. However, long chain triglycerides (LCT) and medium chain triglycerides (MCT) differed in their regional effects on cell proliferation; all four LCT rich diets increased mucosal mass and cell proliferation maximally in the mid small intestine, while MCT had their greatest effect proximally. Subsequently, two groups of eight rats were fed diets in which EFA or MCT were given as twice daily boluses (29% of dietary calories) for 20 to 23 days and compared with a third group of eight rats receiving a glucose rich, low fat diet. EFA and MCT boluses increased the overall parameters of small intestinal mucosal mass and for both oils the effects were now maximal in the mid small intestine. Thus different triglycerides have similar effects on overall small intestinal mucosal mass, but MCT differ from LCT in their regional effects on mucosal cell proliferation when they are given in mixed diets, although not when given as boluses.     

Mucosal Growth and Enzyme Activity during the Early Phase of Adaptation after Jejunal Bypass in the Rat

Morphological variables and mucosal enzyme activities were measured in the bypassed and remaining parts of the small intestine 3, 7, and 14 days after a jejunal bypass operation. In the bypassed segment tissue mass, enzyme activity per unit intestinal length, and enzyme activity per unit DNA were gradually reduced. In sham-operated animals tissue mass increased, whereas enzyme activity per unit DNA was reduced. In the segment remaining in function, tissue mass increased, whereas enzyme activities decreased temporarily. In this part of the intestine, the changes were more or less parallel in bypassed and sham-operated animals. It may be concluded that the enzymatic changes are not correlated to the morphologic changes in the early phase of adaptation to intestinal bypass.