Integrity of the Intestinal Barrier: The Involvement of Epithelial Cells and Microbiota—A Mutual Relationship

The gastrointestinal tract, which is constantly exposed to a multitude of stimuli, is considered responsible for maintaining the homeostasis of the host. It is inhabited by billions of microorganisms, the gut microbiota, which form a mutualistic relationship with the host. Although the microbiota is generally recognized as beneficial, at the same time, together with pathogens, they are a permanent threat to the host. Various populations of epithelial cells provide the first line of chemical and physical defense against external factors acting as the interface between luminal microorganisms and immunocompetent cells in lamina propria. In this review, we focus on some essential, innate mechanisms protecting mucosal integrity, thus responsible for maintaining intestine homeostasis. The characteristics of decisive cell populations involved in maintaining the barrier arrangement, based on mucus secretion, formation of intercellular junctions as well as production of antimicrobial peptides, responsible for shaping the gut microbiota, are presented. We emphasize the importance of cross-talk between gut microbiota and epithelial cells as a factor vital for the maintenance of the homeostasis of the GI tract. Finally, we discuss how the imbalance of these regulations leads to the compromised barrier integrity and dysbiosis considered to contribute to inflammatory disorders and metabolic diseases.

H2S Donors and Their Use in Medicinal Chemistry

Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their -biological applications.

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.

Lipoxygenase Enzymes, Oligosaccharides (Raffinose and Stachyose) and 11sA4 and A5 Globulins of Glycinin Present in Soybean Meal Are Not Drivers of Enteritis in Juvenile Atlantic Salmon (Salmo salar)

Soybean meal has been largely investigated and commercially used in fish nutrition. However, its inclusion levels have been carefully considered due to the presence of antinutritional factors, which depending on a series of factors might induce gut inflammation damaging the mucosal integrity and causing enteritis. Several strategies including genetic engineering have been applied attempting to reduce or eliminate some of the antinutritional factors. Accordingly, we assessed the intestinal health of juvenile Atlantic salmon fed high levels of speciality soybean genotypes with reduced-to-no content amounts of lipoxygenases, altered glycinin profile and reduced levels of oligosaccharides. No major signs of enteritis, only indication of enteritis progression, was noticed in the soybean meal-based diets illustrated by mild changes in distal intestine morphology. Whereas fish, fed fishmeal control feeds, displayed normal distal intestine integrity. Speciality soybean types did not improve intestinal health of juvenile Atlantic salmon suggesting these antinutrients are not drivers of the intestinal inflammatory process in this species. No additional benefits in terms of production performance or blood biochemistry were noticed in the speciality soybean types compared to the traditional soybean.

Is the Gut Microbiome a Target for Adjuvant Treatment of COVID-19?

High expression of the transmembrane protein angiotensin I converting enzyme 2 (ACE2), more than 100-times higher as in the lung, and transmembrane serine protease 2 (TMPRSS2) in the gastrointestinal tract leads to infection with SARS-CoV-2. According to meta-analysis data, 9.8–20% of COVID-19 patients experience gastrointestinal symptoms, where diarrhoea is the most frequent, and about 50% shed viruses with high titre through their faeces, where a first faecal transmission was reported. Furthermore, gut inflammation, intestinal damage, and weakening of the gut mucosal integrity that leads to increased permeability has been shown in different studies for COVID-19 patients. This can lead to increased inflammation and bacteraemia. Low mucosal integrity combined with low intestinal damage is a good predictor for disease progression and submission to the intensive care unit (ICU). Several pilot studies have shown that the gut microbiome of COVID-19 patients is changed, microbial richness and diversity were lower, and opportunistic pathogens that can cause bacteraemia were enriched compared to a healthy control group. In a large proportion of these patients, dysbiosis was not resolved at discharge from the hospital and one study showed dysbiosis is still present after 3 months post COVID-19. Consequently, there might be a link between dysbiosis of the gut microbiome in COVID-19 patients and chronic COVID-19 syndrome (CCS). Various clinical trials are investigating the benefit of probiotics for acute COVID-19 patients, the majority of which have not reported results yet. However, two clinical trials have shown that a certain combination of probiotics is beneficial and safe for acute COVID-19 patients. Mortality was 11% for the probiotic treatment group, and 22% for the control group. Furthermore, for the probiotic group, symptoms cleared faster, and an 8-fold decreased risk of developing a respiratory failure was calculated. In conclusion, evidence is arising that inflammation, increased permeability, and microbiome dysbiosis in the gut occur in COVID-19 patients and thus provide new targets for adjuvant treatments of acute and chronic COVID-19. More research in this area is needed.

Future of Bovine Amniotic Membrane: Bovine Membrane Application on Wound Healing, Surgery and Prospect of Use for Urethral Reconstruction

This chapter describes how bovine amniotic membrane could be indicated for wound healing, especially in complex surgery such as urethral reconstruction. Chemical studies have assessed both histologically and immunohistochemically that bovine amniotic membrane creates scaffold for wound healing. Whereas, clinical studies have shown that bovine amniotic membrane property could be substituted for wound dressing hence improving skin or mucosal integrity. Bovine membrane has been known to be used for many specialties such as ocular surgery, neurosurgery, maxillofacial and orthopedic surgery. This chapter includes such studies and shows the usage possibility of bovine amniotic membrane for other complex defect as shown in urethral reconstruction.

Oral Complications of Head and Neck Cancer Therapy

Current therapies for Head and Neck cancer treatment are extremely advanced. Though, they cause oral complications which have deleterious effects on basic life functions, affect oral and overall health, may lead to significant morbidity and treatment discontinuation and have an impact on survivorship and quality of life. As new therapies are introduced, a new spectrum of oral complications is rising, compromising the mucosal integrity and the salivary function, that may not be recognized, reported and treated properly. Oral complications, often permanent and extremely painful, may include mucositis, xerostomia, dysgeusia, infections, trismus and fibrosis, risk of dental disease and necrosis of the jaw, neurosensory disorders and when targeted therapies and immunotherapy are involved, aphthoid and lichenoid lesions can also be reported. Increased awareness is required for the prevention and management of these complications, which can be best provided by a multidisciplinary team.

Psychological and Gastrointestinal Symptoms of Patients with Irritable Bowel Syndrome Undergoing a Low-FODMAP Diet: The Role of the Intestinal Barrier

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) improves both gastrointestinal (GI) symptoms and the psychological profile of patients with irritable bowel syndrome with diarrhea (IBS-D). The effects of 12 weeks of LFD on GI symptom and psychological profiles in relation to inflammation and the involvement of the intestinal barrier were studied in twenty IBS-D patients. The IBS Severity Scoring System, the Symptom Checklist-90-Revised, the Italian version of the 36-Item Short-Form Health Survey, the IBS-Quality of Life (QoL) questionnaire, and the Psychophysiological questionnaire were administered. The GI barrier function was assessed by sugar absorption test, the serum and fecal zonulin levels, and the serum levels of intestinal fatty-acid binding protein and diamine oxidase. Interleukins (ILs) and lipopolysaccharide (LPS) serum levels were evaluated along with dysbiosis. At the end of LFD, GI symptoms, psychological state (mainly anxiety, somatization, psychoticism, and interpersonal sensitivity), and QoL significantly improved in these patients. Simultaneously, an improvement in small intestinal permeability and intestinal mucosal integrity occurred, while IL-6, Il-10, LPS, and fermentative dysbiosis significantly decreased. The LFD can modify the immune-inflammatory features and enhance intestinal permeability and mucosal integrity, thus determining a concurrent improvement in the clinical and psychological conditions.

Impaired Esophageal Mucosal Integrity and the Related Motility Factors in Refractory Gastroesophageal Reflux Disease

Backgrounds. Research on esophageal mucosal integrity in gastro-oesophageal reflux disease (GERD) has been taken seriously in recent years, especially in refractory GERD. Mean nocturnal baseline impedance (MNBI) is proposed as an indicator of impaired mucosal integrity. We aimed to compare the MNBI value and investigate the impact of esophageal motility on MNBI in different subtypes of refractory GERD. Methods. Endoscopy, high-resolution manometry, and 24h impedance-pH monitoring were performed in 412 refractory GERD patients. From these patients, 94 erosive esophagitis (EE), 52 non-erosive reflux disease (NERD), and 31 Barrett's esophagus (BE) patients were enrolled in the study. EE group 54 included Los Angeles (LA) Grade-A/B and 40 LA Grade-C/D patients. 52 functional heartburn (FH) patients were used as the control. MNBI was acquired at 3 and 5 cm above lower esophageal sphincter (LES) and was compared between groups. Parameters of esophagogastric junction (EGJ) and LES, along with esophageal peristaltic sequences were recorded. Univariate and multivariate regression analysis were performed to determine the impact of these motility factors on MNBI in different subtypes of refractory GERD. Results. MNBI values were signifiantly lower in all subgroups of refractory GERD patients than in FH patients. MNBI in NERD patients was similar with LA-A/B and LA-C/D patients. MNBI in NERD and LA-C/D patients was signifiantly lower than in BE patients. No difference in MNBI was found between LA-A/B and BE patients. Ineffective esophageal motility and absent contractility were the risk factor for decreased MNBI in LA-A/B and LA-C/D patients, respectively. Type III EGJ (hiatus hernias) and decreased LES length were the risk factor for decreased MNBI in NERD and BE patients, respectively. Conclusions. Impaired mucosal integrity of NERD patients was as severe as that of EE patients and hiatus hernias were the risk factor, therefore, mucosal protections and explorations of hiatus hernias should be emphasized in refractory NERD patients. Weakened esophageal body peristalsis and decreased LES length were the risk factor for the impaired mucosal integrity of refractory EE patients and BE patients, respectively, and thus the therapy on peristaltic disorders and LES function was recommended for them. These results provided new ideas for optimizing the treatment of refractory GERD.