Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets

AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model.METHODS: Newborn piglets were allotted at day 4 of age to the following treatments:(1) full-strength formula(FSF)/noninfected;(2) FSF/rotavirus infected;(3) half-strength formula(HSF)/noninfected;or(4) HSF/rotavirus infected.After one day of adjustment to the feeding rates,pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussingchamber analyses.RESULTS: Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection(P < 0.05).Three days post-infection,marked diarrhea and weight loss were accompanied by sharp reductions in villus height(59%) and lactase activity(91%) and increased crypt depth(21%) in infected compared with non-infected pigs(P < 0.05).Malnutrition also increased crypt depth(21%) compared to full-fed piglets.Villus:crypt ratio was reduced(67%) with viral infection.There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition(P = 0.1).3H-mannitol flux was significantly increased(50%;P < 0.001) in rotavirus-infected piglets compared to non-infected piglets,but there was no effect of nutritional status.Furthermore,rotavirus infection reduced localization of the tight junction protein,occludin,in the cell membrane and increased localization in the cytosol.CONCLUSION: Overall,malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.

Bovine immunoglobulin protein isolates for the nutritional management of enteropathy

The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus(HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome(IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function(e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management ofenteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasmaor serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine

AIM： To investigate the effects of lubiprostone and Polyethylene Glycol 3350 （PEG） on mucosal barrier repair in ischernic-injured porcine intestine. METHODS： Ileum from 6 piglets （approximately 15 kg body weight） was subjected to ischemic conditions by occluding the local rnesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer＇s solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance （TER） and mucosal-to-serosal fluxes of ^3H-rnannitol and ^14C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS： Application of 1μmol/L lubiprostone to the rnucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to nontreated tissue. Lubiprostone also reduced mucosal-toserosal fluxes of ^3H-rnannitol and ^14C-inulin. Alternatively, application of a polyethylene laxative （PEG, 20 rnmol/L） to the mucosal surface of ischernic tissues significantly increased flux of ^3H-rnannitol and ^14C-inulin. CONCLUSION： This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.