Painong San, a Traditional Chinese Compound Herbal Medicine, Restores Colon Barrier Function on DSS-Induced Colitis in Mice

Objective. The intestinal barrier decreases in colitis and restores the integrity of the mucosal barriers that could be used for the treatment of colitis. Painong San (PNS), a traditional Chinese compound herbal medicine originally recorded in “Jingui Yaolve” by Zhongjing Zhang in the Later Han Dynasty, is often used in China and Japan to treat various purulent diseases including intestinal carbuncle. This study was to investigate the effect of PNS on mucosal barrier function in mice with DSS-induced colitis and its related mechanisms. Methods. BALB/C mice were given 3% DSS to induce colitis. The body weight and stool status of the mice were recorded daily, and the histopathological changes of the colon were observed after execution. The permeability of the intestinal mucosa was measured by fluorescein isothiocyanate-dextran 4000, the change of intestinal microbiota was measured by 16S rDNA, and the tight junction-related proteins and Muc-2 were investigated by immunohistochemical or immunofluorescence. The possible signaling pathways were detected by western blot. Results. Compared with the control group, the composition of the microbiota in the PNS group was close to that of the normal group, the number of goblet cells was improved, and the mucosal permeability was significantly reduced. PNS could upregulate the expression of tight junction-related proteins (ZO-1, claudin-1, and occludin) and Muc-2, and at the same time, regulate the Notch pathway. Conclusion. PNS could effectively improve the mucosal barrier function through multiple ways, including restoring the balance of intestine flora, enhancement of the mucous layer barrier, and mechanical barrier function. These protective effects may relate to inhibiting the Notch signaling pathway activated by DSS.

The Impact of α-Adrenoceptors in the Regulation of the Hypotonicity-Induced Increase in Duodenal Mucosal Permeability In Vivo

The duodenal mucosa is regularly exposed to a low osmolality, and recent experiments suggest that hypotonicity increases mucosal permeability in an osmolality-dependent manner. The aim was to examine whether the sympathetic nervous system, via action on α-adrenoceptors, affects the hypotonicity-induced increase in duodenal mucosal permeability. The duodenum of anaesthetised rats was perfused in vivo with a 50 mM NaCl solution in the presence of adrenergic α-adrenoceptor drugs. Studied were the effects on mucosal permeability (blood-to-lumen clearance of 51Cr-EDTA), arterial blood pressure, luminal alkalinisation, transepithelial fluid flux, and motility. Hypotonicity induced a six-fold increase in mucosal permeability, a response that was reversible and repeatable. The α2-adrenoceptor agonist clonidine abolished the hypotonicity-induced increase in mucosal permeability, reduced arterial blood pressure, inhibited duodenal motility, and decreased luminal alkalinisation. The α2-adrenoceptor antagonists, yohimbine and idazoxan, prevented the inhibitory effect of clonidine on the hypotonicity-induced increase in mucosal permeability. The α1-agonist phenylephrine or the α1-antagonist prazosin elicited their predicted effect on blood pressure but did not affect the hypotonicity-induced increase in mucosal permeability. None of the α1- or α2-adrenoceptor drugs changed the hypotonicity-induced net fluid absorption. In conclusion, stimulation of the adrenergic α2-adrenoceptor prevents the hypotonicity-induced increase in mucosal permeability, suggesting that the sympathetic nervous system has the capability to regulate duodenal mucosal permeability.

Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis

Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of Lactobacillus was markedly increased and that of Clostridium was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.

Dysbiosis and obesity: implications of the gut microbiota

Introduction: Obesity has been considered a public health crisis, contributing as a risk factor for several important chronic diseases and even death. Considering this fact, it is noteworthy that there is a fundamental relationship between the intestine and health, and this organ is considered by modern medicine as our second brain in the concept of intestinal permeability. Within the evaluation of the food process, effective nutritional absorption can be altered due to imbalances, such as malabsorption, drug-nutrient interaction, changes in mucosal permeability, and, consequently, an imbalance in the gut microbiota. Dysbiosis is characterized by these negative changes that occur in the intestine. In this sense, the present systematic review study sought to answer: What influences can the microbiota composition have on the metabolic syndrome and obesity process? Objective: To elucidate the relationship between the presence of intestinal dysbiosis in the pathogenesis of obesity. Methods: This is a bibliographic review work where the MEDLINE, PubMed, and SciELO databases were consulted using the following descriptors: Human gut microbiota, obesity, dysbiosis. Results and Conclusion: Based on the literature that supports this theme, it was possible to observe that in the obese population there is an increase in bacteria of the genus Firmicutes and a decrease in the genus Bacteriodetes, with the blocking of factors and proteins that regulate the homeostasis of the absorption of lipids and fatty acids being observed thus being able to alter the energy metabolism leading to a greater accumulation of adipose tissue.

Melatonin-Activated Receptor Signaling Pathways Mediate Protective Effects on Surfactant-Induced Increase in Jejunal Mucosal Permeability in Rats

A well-functional intestinal mucosal barrier can be compromised as a result of various diseases, chemotherapy, radiation, and chemical exposures including surfactants. Currently, there are no approved drugs targeting a dysfunctional intestinal barrier, which emphasizes a significant medical need. One candidate drug reported to regulate intestinal mucosal permeability is melatonin. However, it is still unclear if its effect is primarily receptor mediated or antioxidative, and if it is associated with enteric neural pathways. The aim of this rat intestinal perfusion study was to investigate the mechanisms of melatonin and nicotinic acetylcholine receptors on the increase in intestinal mucosal clearance of 51Cr-labeled ethylenediaminetetraacetate induced by 15 min luminal exposure to the anionic surfactant, sodium dodecyl sulfate. Our results show that melatonin abolished the surfactant-induced increase in intestinal permeability and that this effect was inhibited by luzindole, a melatonin receptor antagonist. In addition, mecamylamine, an antagonist of nicotinic acetylcholine receptors, reduced the surfactant-induced increase in mucosal permeability, using a signaling pathway not influenced by melatonin receptor activation. In conclusion, our results support melatonin as a potentially potent candidate for the oral treatment of a compromised intestinal mucosal barrier, and that its protective effect is primarily receptor-mediated.

Intestinal microbiota and inflammatory bowel diseases

Background: The prevalence of inflammatory bowel diseases (IBD) has been rapidly increasing over the past several decades in Korea. IBD appears to be resulted from inappropriate and chronic activation of the mucosal immune system driven by stimuli such as intestinal microbiota and various environmental factors in genetically susceptible individuals.Current Concepts: Recent advances in next-generation sequencing technology have identified alterations in the composition and function of the intestinal microbiota in individuals with IBD. Dysbiosis in patients with IBD is characterized by decreased bacterial diversity combined with an expansion of putative aggressive species and a reduction in protective species. Altered microbial composition and function in IBD correlates with increased immune stimulation, epithelial dysfunction, or enhanced mucosal permeability. Thus, dysbiosis may play an essential role in the pathogenesis of IBD.Discussion and Conclusion: Although it is currently unclear whether dysbiosis is a cause or consequence of intestinal inflammation in IBD, several microbial-based and microbial-targeted therapies have yielded promising early results.

Pendampingan Keluarga dalam Pencegahan dan Perawatan Dispepsia

Dyspepsia is a symptom felt by the patient between the navel and the xyphoid process, including epigastric pain, sensation of pressure and fullness, nausea, and early subjective satiety. The etiology of this disorder is heterogeneous and multifactorial. Contributing causes include impaired motility, visceral hypersensitivity, increased mucosal permeability, and disorders of the autonomic and enteric nervous systems. There is no causally directed treatment for functional dyspepsia. The purpose of this activity is to increase the knowledge of dyspepsia patients and their families regarding how to prevent and treat dyspepsia. Therefore, health education is carried out to increase knowledge of dyspepsia patients and their families about the causes, processes of occurrence, signs and symptoms, dangers, ways of treatment and prevention, how to take medicine, and traditional medicines for dyspepsia. The methods used are lectures, discussions, and demonstrations. The media used were leaflets, posters, pretest and posttest questions. The results of this service activity showed an increase in knowledge in both categories by 50% before and after counseling. It is recommended for the next service in the community so that they can demonstrate directly how to process traditional medicines for dyspepsia. Keyword: Dyspepsia; Family; Prevention; Accompaniment; Care

Gastrointestinal symptoms in SARS-CoV‑2 infected: emphasis on increased mucosal permeability

The article presents data on the prevalence of gastrointestinal symptoms in patients with COVID‑19, the mechanisms of its development, the impact on the course of the disease and the tactics of drug therapy. It is noted that the persistence of the SARS-CoV‑2 virus in the intestine may be responsible for an increase in the duration of the disease and the development of multi-organ lesions, since the intestine, on the one hand, is the site of penetration and replication of the SARS-CoV‑2 virus, and on the other, is a potential source of virus spread due to increased intestinal permeability against the background of infection and disturbed microbiocenosis. Based on this, it seems pathogenetically justified to use drugs in the complex therapy of patients that contribute to the normalization of intestinal microbiocenosis and intestinal permeability.

Rational treatment of patients with functional dyspepsia

Functional dyspepsia is one of the most common functional disorders of the gastrointestinal tract, which resulted from impaired motor skills, visceral hypersensitivity, increased mucosal permeability, disorders of the autonomic nervous system, etc. There is no specific therapy for this disease, which often leads to the irrational use of various groups of drugs. Drug therapy is recommended only during periods of symptoms. The main options of pharmacotherapy include the use of proton pump inhibitors, phytotherapeutic drugs, eradication therapy of Helicobacter pylori. Against the background of possible motor disorders, prokinetics are also one of the possible treatment options, but cisapride has long been withdrawn from sale due to cardiotoxicity, the use of domperidone and metoclopramide is limited due to side effects, especially with long-term therapy, so currently the only prokinetic that can be used in everyday clinical practice is itopride. In refractory cases, tricyclic antidepressants and psychotherapeutic approaches are another effective treatment option.