Current Opinion in Gastroenterology最新文献

Purpose of review: The contributions of intestinal barrier loss, that is, increased permeability, to multiple disorders, including inflammatory bowel disease (IBD), have been a topic of speculation for many years, and the literature is replete with conclusions based on correlation and speculation. The goal of this article is to critically review recent advances in mechanistic understanding of barrier regulation and the evidence for and against contributions of intestinal barrier loss to disease pathogenesis.

Recent findings: It is now recognized that intestinal permeability reflects the combined effects of two distinct routes across tight junctions, which form selectively permeable seals between adjacent epithelial cells, and mucosal damage that leads to nonselective barrier loss. These are referred to as pore and leak pathways across the tight junction and an unrestricted pathway at sites of damage. Despite advances in phenotypic and mechanistic characterization of three distinct permeability pathways, development of experimental agents that specifically target these pathways, and remarkable efficacy in preclinical models, pathway-targeted therapies have not been tested in human subjects.

Summary: After decades of speculation, therapeutic interventions that target the intestinal barrier are nearly within reach. More widespread use of available tools and development of new tools that discriminate between pore, leak, and unrestricted pathway permeabilities and underlying regulatory mechanisms will be essential to understanding the local and systemic consequences of intestinal barrier loss.

Purpose of review: Bidirectional regulation between neurons and immune cells in the intestine governs essential physiological processes, including digestion, metabolism and motility, while also controlling intestinal inflammation and maintaining tissue homeostasis. This review covers recent advances and future research challenges focused on the regulatory molecules and potential therapeutic targets in neuron-immune interactions within the intestine.

Recent findings: Recently identified molecular and cellular pathways have been shown to regulate neuron-immune cell cross talk in the context of maintaining tissue homeostasis, modulating inflammation, and promoting intestinal repair. Additionally, behaviors governed by the central nervous system, including feeding and stress responses, can play key roles in regulating intestinal immunity and inflammation.

Summary: This review emphasizes recent progress in understanding the complex interplay between the nervous system and intestinal immune system and outlines future research directions. These advances have the potential to lead to innovative therapies targeting gastrointestinal disorders including inflammatory bowel diseases, allergic responses and cancer.

Purpose of review: Antibiotics are a cornerstone of modern medicine, but antibiotic consumption can have depleting effects on the gut microbiota, potentially leading to gastrointestinal symptoms and other diseases, namely Clostridioides difficile infection. Because nutrition is a major driver of gut microbiota diversity and function, here we explore the current evidence on the potential of diets in alleviate the deleterious effects of antibiotics consumed during infections.

Recent findings: Beneficial nutrients can enhance the symbiotic effect of the gut microbiota with the host, supporting anti-inflammatory responses and maintaining tight junction integrity. Short-chain fatty acids have been shown to positively affect the immune response, reducing the severity of C. difficile infection, whereas high-fibre diets have been shown to promote faster recovery of the gut microbiota after antibiotic therapy.

Summary: The role of nutrition during infection is gaining momentum, with key findings exploring the effect of some nutrients in limiting the severity of infections and helping the microbiota recover from antibiotic-induced dysbiosis. Although this field is in its infancy, these findings open the possibility of personalised nutrition as a way of restoring microbiome diversity. But more work is needed to identify the most effective types and combinations of nutrients to achieve this.

Purpose of review: We will review the current management of colonic perforations, with particular emphasis on iatrogenic perforations caused by colonoscopy, the leading etiology. We will focus on recently developed endoscopic techniques and technologies that obviate morbid emergency surgery (the standard management approach in years past).

Recent findings: Colonic perforations are rare but potentially fatal complications of both diagnostic and therapeutic colonoscopy resulting in death in approximately 5% of cases with the mortality increasing with delay in diagnosis and treatment. As novel endoscopic techniques and tools have flourished in recent years, our approach to management of these perforations has evolved. With the availability of newer tools such as over the scope clips, enhanced through the scope clips and novel endoscopic suturing devices, colonic perforations can be managed effectively in many or most patients without the morbidity of surgical interventions.

Summary: With expanding use of colonoscopy, inadvertent outcomes such as perforations are bound to increase as well. Early diagnosis permits minimally invasive, nonsurgical, endoscopic management in most cases if the expertise and tools are available. Centers with high colonoscopy volumes including therapeutic procedures would be well served to invest in the requisite technologies and expertise.

Purpose of review: Herein, we present an overview of innovative oral technologies utilized in colonic drug delivery systems that have made significant translational and clinical advancements to treat inflammatory bowel disease (IBD) in recent years.

Recent findings: The colon is home to distinct physiological conditions, such as pH and microbiota, that have been exploited in the development of colonic drug delivery systems for the treatment of local and systemic diseases. However, given the intra and interindividual variability in the gastrointestinal tract of both healthy and diseased states, various systems have shown inconsistencies in targeted drug release to the colon. Recent breakthroughs have led to systems that incorporate multiple independent trigger mechanisms, ensuring drug release even if one mechanism fails due to physiological variability. Such advanced platforms have bolstered the development of oral biologics delivery, an especially promising direction given the lack of commercially available oral antibody medications for IBD. These concepts can be further enhanced by employing 3D printing which enables the personalisation of medicines.

Summary: Leveraging these novel technologies can accurately deliver therapeutics to the colon, allowing for treatments beyond gastrointestinal tract diseases. To realize the full potential of colonic drug delivery, it is paramount that research focuses on the clinical translatability and scalability of novel concepts.

Purpose of review: The aim of this review is to present the current state of the field, highlight recent developments, and describe the clinical outcomes of endoscopic therapies for bariatric surgery complications.

Recent findings: The field of interventional endoscopy now presents a range of minimally invasive procedures for addressing postbariatric complications. Lumen-opposing metal stents have emerged as a reliable solution for managing gastrojejunal strictures following Roux-en-Y gastric bypass, whether with or without associated leaks. Additionally, they serve as a conduit for performing endoscopic retrograde cholangiopancreatography (ERCP) post-RYGB via EUS-directed ERCP (EDGE). Gastric peroral endoscopic myotomy, originally designed for gastroparesis, has demonstrated effectiveness in treating postgastric sleeve stenosis, particularly the challenging helical stenosis cases. Furthermore, innovative endoscopic antireflux techniques are showing encouraging outcomes in addressing gastroesophageal reflux disease (GERD) following sleeve gastrectomy. Additionally, several modifications have been proposed to enhance the efficacy of transoral outlet reduction (TORe), originally developed to treat weight regain due to gastrojejunal anastomotic issues post-RYGB.

Summary: Endoscopic management of bariatric surgery complications is continuously evolving. The development of new techniques and devices allows endoscopists to provide novel, minimally invasive alternatives that were not possible in the near past. Many techniques, however, are limited to expert centers because they are technically demanding, and specialized training in bariatric endoscopy is still required.

Purpose of review: Although the mucosal barrier serves as a primary interface between the environment and host, little is known about the repair of acute, superficial lesions or deeper, persistent lesions that if not healed, can be the site of increased permeability to luminal antigens, inflammation, and/or neoplasia development.

Recent findings: Studies on acute superficial lesions have been sparse in the past year, with more focus given to novel mechanisms of mucosal protection, and the way in which mature epithelial cells or committed stem cells dedifferentiate, reprogram, proliferate, and then regenerate the gastroduodenal mucosa after injury. For this, adenoviral therapy showed organ specific targeting with mRNA and protein expression of effectors to protect against mucosal injury and ulceration. A large database of plant-based agents known to protect against injury and ulceration was published, along with studies using plant-based compounds delivered with alginates, polysaccharide/gel floating rafts, or incorporated into nanoparticles or green carbon dots to improve targeting and retention at the ulcerated lesion. With RNA technology developing rapidly, particularly single-cell RNA sequencing, important and novel data was forthcoming on mucosal regeneration. In particular, the role of interleukin-17 hub proteins in mucosal healing was highlighted. The presence and role of injury reserve cells was determined, as was the composition of ligand gradients for cell differentiation in both stomach and duodenum. The role of amphiregulin in parietal cell differentiation from lineage-restricted stem cells and the Yap1 gene signature in metaplasia vs. healing ulcers were of particular importance. Additionally, studies unveiled the important role of mesenchymal stromal cells in differentiation and repair mechanisms, in Muse cells as an exciting new therapy for mucosal repair after injury, and the role of sympathetic neurons in activating the immune system to regulate mucosal repair mechanisms.

Summary: Recent studies highlight novel mechanisms that promote mucosal regeneration after injury of the gastroduodenal mucosa.

Purpose of review: This review highlights recent research in the field of celiac disease.

Recent findings: Epidemiological studies continue to identify celiac disease-associated diseases such as inflammatory arthritis, irritable bowel syndrome, and cardiovascular disease. Recently published consensus guidelines provide recommendations for the long-term management and monitoring of patients with celiac disease. There are multiple pharmaceutical therapies for celiac disease under investigation, and recent phase I and phase II trials are reviewed here. Finally, a recent trial of patients with nonceliac gluten sensitivity demonstrates a significant nocebo effect in this condition.

Summary: Recent advances in celiac disease include the development of new clinical guidelines as well as promising new therapeutics. Continued high-quality research is needed to improve the outcomes of patients with celiac disease and nonceliac enteropathies.

Purpose of review: Functional dyspepsia is a common gastrointestinal disease that is under-recognized and under-diagnosed. It is a complex disorder of gut-brain interaction with no FDA-approved treatment options. The purpose of this review is to highlight updates in the proposed pathophysiology and present new data regarding potential therapies for functional dyspepsia.

Recent findings: Alterations in the intestinal microbiome and integrity of the intestinal membrane may play a crucial role in the pathogenesis of functional dyspepsia. The low FODMAP diet, in addition to modulating the microbiome with antibiotics and probiotics, are targets for large future studies. Novel methods of delivery of gut-brain therapies have shown promising results, especially virtual reality.

Summary: The pathophysiology and management of functional dyspepsia is complex and there is still much unknown; however, continued research is identifying new targets for treatment. New and more targeted treatment options provide clinicians a variety of tools to offer patients with functional dyspepsia.