Intestinal permeability in humans is increased after radiation therapy

PURPOSE: Irradiation inflicts acute injuries to the intestinal mucosa with rapid apoptosis induction and subsequent reduction in epithelial surface area. It may therefore be assumed that the intestinal barrier function is affected. The aim of this study was to compare the mucosal permeability in irradiated rectum and nonirradiated sigmoid colon from patients subjected to radiation therapy before surgical treatment for rectal cancer. METHODS: Segments from sigmoid colon and rectum obtained from irradiated and nonirradiated patients were stripped from the serosa-muscle layer and mounted in Ussing diffusion chambers. The mucosa-to-serosa passage of the marker molecules 14C-mannitol, fluorescein isothiocyanate-dextran 4,400, and ovalbumin was followed for 120 minutes. RESULTS: The permeability to the markers was size-dependent and increased linearly across time in all specimens. The passage of all markers was increased in irradiated rectum compared with nonirradiated sigmoid colon, whereas in specimens from nonirradiated patients there were no differences between rectum and sigmoid colon. Histologic signs of crypt and mucosal atrophy were found in the irradiated rectal specimens. CONCLUSIONS: Early gastrointestinal complications after radiation therapy may be the result of mucosal atrophy in addition to mucosal damage, with a loss of barrier integrity

Exogenous leptin controls the development of the small intestine in neonatal piglets

Leptin, a hormone produced and secreted by adipose tissue, muscles and stomach, is involved in the regulation of adipose tissue mass, food intake and body weight in neonatal animals. It is also produced in the mammary glands and secreted into the colostrum and milk. Since leptin receptors are widely distributed in the small intestine mucosa, the aim of the present study was to investigate the effect of exogenous leptin on the development of the small intestine in neonatal piglets. Male neonatal piglets were fed with sow's milk or artificial milk formula. Every 8 h the latter received either vehicle or leptin (2 or 10 mug/kg body weight). The animals were either killed after 6 days of treatment and the small intestine sampled for histology and brush border enzyme activities or were tested for marker molecule (Na-fluorescein and BSA) absorption in vivo. Feeding milk formula slowed the maturation of small intestinal mucosa compared with feeding sow's milk. However, after leptin treatment the length of the small intestine was increased, and intestinal villi length, but not crypt size, was reduced compared with controls. The mitotic index was increased and the percentage of vacuolated enterocytes was reduced in the entire small intestine. Enterocyte brush border protease and lactase activities were reduced in the jejunum. Na-fluorescein marker molecule absorption did not change but that of BSA was reduced 3(.)8-fold. In conclusion, exogenous leptin administered in physiological doses reversed the maturation of the small intestinal mucosa to the range found in sow-reared piglets

Differences in transport rate of oxytocin and vasopressin analogues across proximal and distal isolated segments of the small intestine of the rat.

The transmural intestinal passage of some oxytocin and vasopressin analogues (oxytocin, OT; [Mpa1, D-Arg8]vasopressin, dDAVP; [Mpa1, Tyr (OMe)2, carba6]oxytocin, carbetocin; [Mpa1, D-Tyr (OEt)2, Thr4, Orn8]vasotocin, antocin II; [Mpa1, D-Tyr (OEt)2, Thr4, desPro7Orn8Gly9NH2]tocinoic acid-NH(CH2)3NH2, desPOG-antocin II-NH(CH2)3NH2) was studied using isolated proximal and distal segments in the rat. All peptides (measured as peptide-like immunoreactivity) displayed a higher transport rate across distal intestinal segments as determined by radioimmunoassay (RIA). The smallest peptide, des POG-antocin II-NH(CH2)3NH2, was transported at the fastest rate. No correlation of lipophilicity with transport rate was observed. Determination of the amount of peptide remaining in the mucosal media at the end of the incubation period by HPLC did not reveal any visible degradation products. However, the large difference in transport rate between [3H]OT and immuno-reactive OT indicates mucosal metabolism of this peptide. [3H]d-DAVP was distributed in a larger mucosal volume than the extracellular space marker [3H]inulin, indicating tissue uptake, but was too low

Effect of short chain fatty acids infused intraileally on interdigestive exocrine pancreatic secretions in growing pigs

The effect of intraileally infused short chain fatty acids (SCFA) and saline as control on the exocrine pancreatic secretions during the interdigestive phase was studied using three 8-weeks-old piglets. Pigs were surgically fitted with a pancreatic duct catheter, re-entrant duodenal T-cannula for collection and subsequent return of pancreatic juice, and with an infusion T-cannula at the distal ileum. Saline as control, 5.0 and 10.0 mm butyrate, 7.5 and 15.0 mm propionate and 85.0 and 170.0 mm acetate were infused at 2 ml/kg body weight (BW) for 30 min into the ileum of overnight fasted piglets via ileal T-cannula. The calculated volume of infusates was administrated in five equal bolus at 6 min intervals over a period of 30 min. The pancreatic juice was collected 60 and 30 min before and 30, 60, 90 and 120 min after the start of infusion. The trypsin ( p = 0.07, p > 0.15 respectively) and protein ( p > 0.15, p = 0.05 respectively) outputs immediately decreased after the infusion of acetate at the dose of 85.0 and 170.0 mm, respectively, whereas pancreatic juice outflow ( p > 0.15) was not significantly affected when compared with levels 30 min before infusion. After the infusion of butyrate at the dose of 5.0 mm, trypsin ( p = 0.01) and protein ( p = 0.12) outputs increased immediately whereas pancreatic juice outflow was not affected ( p > 0.15) in comparison with levels 30 min before infusion. No significant differences were observed after infusion of butyrate at the dose of 10 mm for the pancreatic juice outflow, trypsin and protein outputs when compared with the level before infusion, although these values were numerically lower immediately after the infusion. The pancreatic juice outflow increased ( p = 0.03) after the infusion of propionate at the dose of 7.5 mm and decreased ( p = 0.005) immediately after the infusion of propionate at the dose of 15.0 mm when compared with the levels 30 min before the infusions. After the infusion of propionate at the dose of 7.5 or 15.0 mm for the output of protein and trypsin, no significant differences ( p > 0.15) were observed when compared with levels 30 min before infusion. In summary, the intraileal infusion of SCFA at different doses exerts a short-term and moderate effect on the interdigestive exocrine pancreatic secretions in pigs

Dietary green-plant thylakoids decrease gastric emptying and gut transit, promote changes in the gut microbial flora, but does not cause steatorrhea

Green-plant thylakoids increase satiety by affecting appetite hormones such as ghrelin, cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The objective of this study was to investigate if thylakoids also affect gastrointestinal (GI) passage and microbial composition. To analyse the effects on GI passage, 16 rats were gavage-fed a control or thylakoid-supplemented high-fat diet (HFD) 30 min before receiving Evans blue. Another 16 rats were fed a control HFD or thylakoid HFD for two weeks prior to the intragastric challenge with Evans blue. The amount of Evans blue in the stomach and the distance of migration in the intestines after 30 min were used as a measurement of gastric emptying and intestinal transit. These were reduced by thylakoid supplementation in the acute study, and however not significantly also after the two-week diet study. The second aim of the study was to investigate if thylakoid-supplementation affects the gut microbiota and amount of faecal fat in healthy human volunteers (n = 34) receiving thylakoid or placebo treatments for three months. Microbiota was analysed using 16S rRNA gene sequencing and qPCR, and faecal fat was extracted by dichloromethane. The total bacteria, and specifically the Bacteriodes fragilis group, were increased by thylakoid treatment versus placebo, while thylakoids did not cause steatorrhea. Dietary supplementation with thylakoids thus affects satiety both via appetite hormones and GI fullness, and affects the microbial composition without causing GI adverse effects such as steatorrhea. This suggests thylakoids as a novel agent in prevention and treatment of obesity

Spray-dried porcine plasma and yeast derived protein meal influence the adaption to weaning of primiparous and multiparous sow progeny in different ways

Pigs from 154 litters (n = 1132, 19 +/- 3 days of age, 4.9 +/- 1.1 kg of bodyweight) were used in a 3 x 2 factorial design to evaluate two raw materials with nutraceutical properties being used in feeds, spray-dried porcine plasma (SDPP) and a yeast protein meal, and their effects on growth performance, immune parameters and gastrointestinal adaption of piglets to weaning. Factors included dietary treatments being (1) 5% SDPP (PLA), (2) 3.5% yeast protein meal (NUP) and (3) medicated control (TMC) and parity (primiparous versus multiparous). The treatment groups were imposed from Day 19 through to weaning at Day 27. Selected pigs (n = 720, 28 +/- 3 days of age, 7.4 +/- 1.0 kg of bodyweight) were weaned and remained on their respective diets from Day 28 to Day 34. From Day 35 to Day 48 all group-housed pigs were offered a commercial weaner 1 diet, and from Day 49 to Day 68 pigs were offered a commercial weaner 2 diet. Growth performance, survival, and serum immunoglobulinGwere monitored throughout the nursery phase (Day 28 to Day 68). Adaptation of the gastrointestinal tract in the acute post-weaning phase (Day 28 to Day 34) was assessed in 36 individually housed male weaners, with the effects of feed on structural, digestive, microbial and immune parameters along the gastrointestinal tract determined atDay 34. Pre-weaning feed disappearance was greater (P< 0.01) in multiparous litters independent of diet. In the commercial nursery, total removals (mortality and morbidity) were highest (P<0.01) in primiparous sow progeny, with pigs offered NUP having greater (P <= 0.05) total removals. Pigs offered PLA had superior average daily gain, average daily feed intake and feed conversion ratio from Day 28 to Day 34 (P<0.05). Pigs offered NUP tended to (P=0.07) have superior average daily gain from Day 35 to Day 49. Pigs offered NUP had higher (P<0.05) serum immunoglobulinGconcentrations at Day 68 compared with pigs offered TMC, with the effect most pronounced in primiparous sow progeny. Individually housed weaners offered PLA consumed more (P<0.05) feed on Day 30 to Day 31, had shorter relative intestine length (P<0.05), greater villous height in the medial jejunum (P<0.10) and lower immuno-pathology scores along the intestine. Pigs offered PLA also tended (P<0.10) to have increased pancreatic-specific lipase and amylase activity compared with pigs offered NUP. Pigs offered NUP had a higher ratio of E. coli : coliforms in the colon (P<0.01) and more counts of beta-haemolytic bacteria in the medial jejunum (P<0.05) and colon (P<0.10). Diets containing either SDPP or NUP offered pigs benefits beyond nutrition relative to the medicated control diet. The benefits of SDPPwere highly effective but transient, while the yeast derived protein had a successive or accumulative effect which was more pronounced in primiparous sow progeny. Received 3 May 2012, accepted 17 October 2012, published online 29 November 201