Cholera toxin induces intestinal secretion in an acute renal failure rat model

Background: Cholera is a life-threatening secretory diarrheal disease caused by Vibrio cholera bacterium. On the contrary, local and specific use of cholera toxin (CT) at a low concentration can cause controlled fluid secretion. In the study, we explored the secretory action of CT in the intestine of rats with acute renal failure (ARF). Methods: Closed intestinal loop experiments were performed in ARF rats treated with CT. Secreted fluid and serum were analyzed for various ¬solutes and electrolytes. The presence of K+, Na+, Cl-, urea and creatinine were monitored. Histopathology analysis was carried out to evaluate the effect of CT in liver, kidney, and intestinal tissues. Results: A reduction in the absorption of water and electrolytes was observed over time and a secretory response started to appear within hours of CT treatment. The fluid secretory response with entrapped electrolytes was profound in ARF rats. Histopathological analysis of CT exposed tissues revealed that apart from the tissue damage produced by acute renal failure, no CT induced cellular changes occurred. Conclusion: CT can be used as a secretagogue to induce fluid and electrolyte secretion in ARF rats. However, effective measures should be taken to avoid CT induced acidosis.

Thioredoxin Reductase 3 Suppression Promotes Colitis and Carcinogenesis via Activating Pyroptosis and Necrosis

Background Txnrd3 as selenoprotein play key roles in antioxidant process and sperm maturation. Inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease are becoming significantly increasing disease worldwide in recent years which are proved relative to diet especially selenium intake. Methods In the present study, 8-week-old C57BL/6N male Txnrd3-/-, Txnrd3-/+, Txnrd3+/+ mice weight 25-30g were randomly chosen and each group 30 mice. Feed 3.5% DSS drinking water and normal water continuously for 7 days. Mouse colon cancer cells (CT26) were cultured in vitro to establish Txnrd3 overexpressed/knocked-down model by cell transfection technology. Morphology and ultrastructure, calcium levels, ROS level, cell death were observed and detected in vivo and vitro. Results Ulcerative colitis was more severe, morphological and ultrastructural lesions were extremely significant in Txnrd3-/- mice based on the fact that expression of NLRP3, Caspase1, RIPK3, MLKL related to pyroptosis and necrosis pathway was significantly increased. Overexpression of Txnrd3 could lead to increased oxidative stress through intracellular calcium outflow induced oxidative stress increase. Followed by necrosis and pyroptosis pathway activation and further inhibit the growth and proliferation of colon cancer cells. Conclusion Txnrd3 overexpression leads to intracellular calcium outflow, endoplasmic reticulum stress, and increased ROS, which eventually leads to necrosis and focal death of colon cancer cells, while Txnrd3-/- mice depth of the crypt deeper, weakened intestinal secretion and immune function. And aggravate the occurrence of ulcerative colitis. The present study lays a foundation for the prevention and treatment of ulcerative colitis and colon carcinoma in clinic treatment.

The Metabolite β-Hydroxybutyrate of Lactobacillus Plantarum YZX21 Improves Type 2 Diabetes By Promoting Intestinal Secretion of GLP-1

Background: Probiotics and their metabolites regulate type 2 diabetes mellitus (T2DM) by promoting GLP-1 secretion, but the mechanism has not yet been fully clarified. Results: In order to reveal the effect of Lactobacillus plantarum（L. plantarum）YZX21 on the regulation of T2DM, type 2 diabetic C57BL/6 mice induced by a high-fat diet and streptozotocin (STZ) were divided into different groups and were daily treated with L. plantarum YZX21 for 8 weeks. We identified that L.plantarum YZX21 reduced blood glucose, insulin levels and HOME-IR. Histopathology was found that L.plantarum YZX21 restored the mouse islet cells morphology and increased insulin secretion. The Elisa and immumohistochemical staining revealed concentration of glucagon-like peptide-1 (GLP-1) was increased in the mice colon. UPLC-MS/MS based widely-targeted metabolomics analysis was used to identify the differential intestinal metabolites in the mice colon. It was found that the metabolite β-Hydroxybutyrate(BHB) of L.plantarum YZX21 had a negative associated with T2DM. Subsequent, type 2 diabetic C57BL/6 mice was established and used to verify hpyerglycemic effest by daily treated with BHB for 8 weeks. It was found that BHB improved pathoglycemia, insulin resistance and increased the intestinal GLP-1 levels, especially reduced free fatty acid (FFA) levels. The expression of receptors G protein-coupled receptor (GPR) was verified by RT-PCR. The GPR109a receptor was significantly stimulated which was up-regulated the expression of GLP-1, but not GPR41 and GPR43 in the mice colon.Conclusions: We found that the hypoglycemic effect of L.plantarum YZX21 was demonstrated by increasing the intestinal GLP-1 levels in the diabetic mice. Through the widely-targeted metabolomics, we identify the close correlation between serum concentrations of BHB and T2DM. In T2DM mice model, BHB reduced the FFA levels and increased the intestinal GLP-1 levels, which is associated with the downregulated expression of GPR109a. These results demonstrated that L.plantarum YZX21 alleviated T2DM by upregulating BHB/GPR109a/GLP-1 associated pathway.

Intestinal Failure and Short Bowel Syndrome in Crohn’s Disease: A Systematic Review

Crohn's disease (CD) is an inflammatory, chronic and progressive disease that affects the digestive tract. Despite optimized drug therapy, the risk of multiple surgical interventions over the years is high, leading the patient to develop short bowel syndrome (SBS). Thus, adequate management in the postoperative period directly interferes with the long-term prognosis. Initially, most of these patients, due to hydro electrolytic disorders and absorptive incapacity inherent in SBS, will need parenteral nutritional support. According to the patient's residual digestive profile and according to nutritional management (oral, enteral, and/or parenteral), the intestine will evolve in its adaptive capacity. During this period, control agents are used for motility and intestinal secretion and, if necessary, GLP-2 agonists (intestinotrophic). In cases refractory to these treatments, we can still indicate surgical procedures to control motility, increasing intestinal length, and, finally, transplantation. CD is recurrent, and patients with SBS need a multidisciplinary approach with continuous monitoring to provide better intestinal rehabilitation and consequent quality of life.

Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and Improving the Gut Microbiota

BackgroundBerberine is a plant alkaloid that has multiple beneficial effects against intestine inflammation. In our previous study, we have found that berberine also possesses an antidiabetic effect. However, whether berberine is useful in the prevention of type 2 diabetes mellitus (T2DM) through its effect on intestine endocrine function and gut microbiota is unclear.AimTo investigate the effects of berberine in the prevention of T2DM, as well as its effects on intestine GLP-2 secretion and gut microbiota in ZDF rats.MethodsTwenty Zucker Diabetic Fatty (ZDF) rats were fed a high-energy diet until they exhibited impaired glucose tolerance (IGT). The rats were then divided into two groups to receive berberine (100 mg/kg/d; berberine group) or vehicle (IGT group) by gavage for 3 weeks. Five Zucker Lean (ZL) rats were used as controls. Fasting blood glucose (FBG) was measured, an oral glucose tolerance test was performed, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Intestinal expression of TLR-4, NF-κB, TNF-α, mucin, zona occludens-1 (ZO-1) and occludin were assessed (immunohistochemistry). Plasma levels and glutamine-induced intestinal secretion of glucagon-like peptide-1 (GLP-1) and GLP-2 were measured (enzyme-linked immunosorbent assay). The plasma lipopolysaccharide (LPS) level was measured. Fecal DNA extraction, pyrosequencing, and bioinformatics analysis were performed.ResultsAfter 3 weeks of intervention, diabetes developed in all rats in the IGT group, but only 30% of rats in the berberine group. Treatment with berberine was associated with reductions in food intake, FBG level, insulin resistance, and plasma LPS level, as well as increases in fasting plasma GLP-2 level and glutamine-induced intestinal GLP-2 secretion. Berberine could increase the goblet cell number and villi length, and also reverse the suppressed expressions of mucin, occludin, ZO-1 and the upregulated expressions of TLR-4, NF-κB and TNF-α induced in IGT rats (P<0.05). Berberine also improved the structure of the gut microbiota and restored species diversity.ConclusionBerberine may slow the progression of prediabetes to T2DM in ZDF rats by improving GLP-2 secretion, intestinal permeability, and the structure of the gut microbiota.

Glutamatergic plasticity within neurocircuits of the dorsal vagal complex and the regulation of gastric functions

The meticulous regulation of the gastrointestinal (GI) tract is required for the co-ordination of gastric motility and emptying, intestinal secretion, absorption, and transit as well as for the overarching management of food intake and energy homeostasis. Disruption of GI functions is associated with the development of severe GI disorders as well as the alteration of food intake and caloric balance. Functional GI disorders as well as the dysregulation of energy balance and food intake are frequently associated with, or result from, alterations in the central regulation of GI control. The faithful and rapid transmission of information from the stomach and upper GI tract to second order neurons of the nucleus of the tractus solitarius (NTS) relies on the delicate modulation of excitatory glutamatergic transmission, as does the relay of integrated signals from the NTS to parasympathetic efferent neurons of the dorsal motor nucleus of the vagus (DMV). Many studies have focused on understanding the physiological and pathophysiological modulation of these glutamatergic synapses, although their role in the control and regulation of GI functions has lagged behind that of cardiovascular and respiratory functions. The purpose of this review is to examine the current literature exploring the role of glutamatergic transmission in the DVC in the regulation of Gl functions.

Effects of Cola anomala (K. Schum.) water/ethanol pods extract on the inflammation and intestinal secretion in lipopolysaccharide-induced diarrhea

Diarrhea is one of the leading causes of death among children in low and low-middle income countries and the management of this pathology is still a problem in these regions. The water/ethanol extract of the pods of Cola anomala (KEO) has been shown to possess antimicrobial and antidiarrheal effects in Shigella flexneri-induced diarrhea, but whether KEO is active on the toxemic part of this diarrhea is unknown. This study was undertaken to evaluate the effects of KEO on the intestinal secretion and inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS). KEO obtained by maceration in water/ethanol (1:1) was administered orally (25, 50 and 100 mg/kg of body weight) against LPS-induced diarrhea in mice. The mass of feces, the intestinal nitric oxide (NO) and prostaglandin (PGE2) contents as well as myeloperoxidase (MPO) activity were assessed. KEO was also tested on LPS-induced enteropooling in rats. In this experiment, the intestinal fluid and its electrolytes (Na+, K+ and Cl-) contents were determined as well as NO, PGE2, TNF-α and IL-1β levels in the small intestine homogenate. Indomethacin (5 mg/kg) was used as reference drug. KEO significantly (p < 0.001) reduced stools excretion, NO content and MPO activity in intestine but did not affect PGE2 in LPS-induced diarrhea. On the enteropooling model, KEO showed no effect on the intestinal fluid and electrolyte excretion, PGE2, TNF-α and IL-1β contents, but significantly (p < 0.05) reduced the NO production. This study suggests that KEO does not have antisecretory effect, but has anti inflammatory activities. It can be concluded that the anti-toxemic effect of KEO contributes less to its antidiarrheal activity in infectious diarrhea.

Intestine motility, secretion, and constipation treatment principles

Introduction. Constipation is a derangement of the motor, secretory and/or evacuation function of the colon. The same symptoms are recorded in at least 20% of the population in the developed countries – as those occurring sporadically or for a long period.Basic content. The secretory function of the colon significantly affects stool consistency and its free movement. The secretion increases by 8–10 times in the presence of local mechanical irritation. Intestinal mucus is produced by colonic goblet cells. The frequency, time of defecation and stool consistency is in large part determined by the motor function of the colon. The relation of various types of contraction varies depending on the main function – propulsion or mixing. Rhythmic phasic contractions in the colon generate a pendular movement with slow propulsion of the contents and absorption of water. The tonic contractions enhance the mixing effect of weak rhythmic contractions. The propulsive contractions are specifically attributed to the lower gastrointestinal tract and occur spontaneously. They occur quite regularly, from 2 to 10 times a day, and ensure the propulsion of intestinal contents over great distances in the colon. When reaching the sphincter area, such wave causes its relaxation by mechanisms of descending inhibition. The dietary regime and adequate intake of carbohydrates with various chain lengths, including dietary fiber, as well as flavonoids and other components that modify peristaltic activity and secretion, play an important role in the regulation of intestinal secretion and peristalsis. The drugs enhancing intestinal secretion and peristalsis, such as bisacodyl and sodium picosulfate, are also used to treat constipation. These substances hydrolyse into bis-(p-hydroxyphenyl)-pyridyl-2-methane in the intestine, which, upon contact with the receptors in colonic mucosa, stimulates propulsive activity and increases intestinal secretion. The selective action of sodium picosulfate is confined to the colon.Conclusion. Pharmacological and non-pharmacological treatments for constipation are aimed at maintaining and enhancing the natural propulsive contractions of the colon and intestinal secretion.

Treatment of Congenital Chylothorax Using High-Dose Octreotide

Introduction: Neonatal chylothorax is a rare and potentially life-threatening condition with a reported incidence of 1 in 5,800 - 24,000 and a high mortality rate of up to 64%. Octreotide is one of the treatment options available to reduce both the splanchnic blood flow and the intestinal secretion of electrolytes and water. However, there is no uniform guideline for the optimal dosage of octreotide in the treatment of congenital chylothorax. Case Presentation: We present the case of a neonate diagnosed with congenital chylothorax. At birth, the neonate manifested severe respiratory distress warranting cardiopulmonary resuscitation for 25 min. During admission, intravenous octreotide treatment was initiated and feeding was changed from breast milk to a medium-chain triglyceride-enriched formula. Bilateral hilar enlargement and diffusely increased opacities waxed and waned, and we gradually increased the octreotide dosage daily by 1 ~ 2 mcg/kg/h. After 3 days of octreotide administration at the rate of 20 mcg/kg/h, chest x-ray showed regression of pleural effusion. The patient was discharged with full bottle feeding achieved. Conclusions: High-dose octreotide therapy (with doses up to 20 mcg/kg/h) may be recommended for patients with idiopathic congenital chylothorax. However, patients should be carefully monitored for side-effects such as hyperglycemia, necrotizing enterocolitis, transient hypothyroidism, and ileus.