Depression and the Aberrant Intestinal Microbiome.

Depression is one of the most common mental health disorders affecting adults in the United States. The current treatment is the combination of pharmacotherapy and psychotherapy. Recently, the evidence linking gut microbiome dysregulation to the development of depression has grown. The pathophysiology is currently poorly understood, although leading hypotheses include involvement of the hypothalamic-pituitary-adrenal axis, a bidirectional relationship between the gut microbiome and the central nervous system, and production of signaling molecules by the gut microbiome. Available and emerging treatments of the aberrant microbiome include antidepressants, antibiotics, diet modification, probiotics, and fecal microbiota transplant. This article explores the interconnectivity of gut microbiota and depression and treatments targeted toward the gut, reviews the gastroenterologist's potential role in managing gut dysbiosis in patients with depression, and highlights research topics to be addressed to create evidence-based guidelines.

Current and Emerging Therapeutic Options for Gastroparesis.

Gastroparesis is a complex, debilitating dysmotility disorder with challenging symptom management. A diagnosis of gastroparesis is based on objectively delayed gastric emptying in the absence of mechanical obstruction. Given the limited efficacy of treatment options and serious side effects, significant research continues for therapeutic options for gastroparesis. Promising investigational pharmacologic therapies include relamorelin, prucalopride, and aprepitant. A novel endoscopic therapy is gastric peroral endoscopic pyloromyotomy, which is associated with improved gastric emptying. This article reviews both current and emerging therapeutic options for gastroparesis, including dietary modification and pharmacologic, electrical stimulation, endoscopic, and surgical therapies. Further research and novel treatment options are needed to address the substantial morbidity of gastroparesis.

Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer.

Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation.

The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders.

In addition to drugs approved by the US Food and Drug Administration (FDA) that treat, cure, or mitigate disease, medical foods are a tool to help manage chronic conditions and diseases. A medical food, according to the FDA, is a food that is developed to be eaten or administered enterally under the guidance of a physician and that is meant for the specific dietary management of a condition or disease for which distinctive nutritional requirements, based upon known scientific principles, are established by medical evaluation. A variety of medical foods exist to help manage a wide range of medical conditions, from Alzheimer disease to HIV-associated enteropathy. EnteraGam contains serum-derived bovine immunoglobulin/protein isolate, which has been studied extensively in diarrhea-predominant irritable bowel syndrome, inflammatory bowel disease (IBD), and HIV-associated enteropathy. VSL#3 is a probiotic that is used in pouchitis for patients with ulcerative colitis as well as irritable bowel syndrome. Modulen IBD is a whole-protein, sole-nutrition formulation used to manage the active phase of Crohn's disease. Vivonex is an elemental diet that is used in a variety of diseases associated with severe gastrointestinal dysfunction. Medical foods are safe and must have proven efficacy in helping to manage a variety of gastrointestinal conditions and diseases. These therapies represent tools that can be used prior or in addition to traditional medical therapies. This article discusses the history and development of medical foods under the FDA and concentrates specifically on medical foods used to help manage diseases of the gastrointestinal tract.

Sleep Dysfunction and Gastrointestinal Diseases.

Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases.

Fecal Microbiota Transplantation: A Review of Emerging Indications Beyond Relapsing Clostridium difficile Toxin Colitis.

The symbiotic relationship between gut microbiota and humans has been forged over many millennia. This relationship has evolved to establish an intimate partnership that we are only beginning to understand. Gut microbiota were once considered pathogenic, but the concept of gut microbiota and their influence in human health is undergoing a major paradigm shift, as there is mounting evidence of their impact in the homeostasis of intestinal development, metabolic activities, and the immune system. The disruption of microbiota has been associated with many gastrointestinal and nongastrointestinal diseases, and the reconstitution of balanced microbiota has been postulated as a potential therapeutic strategy. Fecal microbiota transplantation (FMT), a unique method to reestablish a sustained balance in the disrupted microbiota of diseased intestine, has demonstrated great success in the treatment of recurrent Clostridium difficile infection and has gained increasing acceptance in clinical use. The possibility of dysfunctional micro-biota playing a causative role in other gastrointestinal and nongas-trointestinal diseases, therefore, has also been raised, and there are an increasing number of studies supporting this hypothesis. FMT is emerging as a feasible therapeutic option for several diseases; however, its efficacy remains in question, given the lack of clinical trial data. Altering microbiota with FMT holds great promise, but much research is needed to further define FMT's therapeutic role and optimize the microbiota delivery system.

Emerging therapeutic options for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus that often occurs in atopic persons. Management strategies include pharmacotherapy, dietary modification, and endoscopic therapy, although patients will often have a relapsing and remitting course. Currently, the primary pharmacotherapy for EoE consists of corticosteroids. Immuno-modulators, leukotriene antagonists, biologies, and monoclonal antibodies are currently under study for treatment of EoE. The role of immunoglobulin E-mediated allergic reactions has been well documented and may provide insight into the etiology and effective therapy of EoE.

Emerging therapeutic options for celiac disease: potential alternatives to a gluten-free diet.

Celiac disease is an autoimmune disorder of the small intestine that is more common than was previously thought. This disease is caused by an inappropriate immune response to wheat gluten, barley, and rye. Three main pathways cause celiac disease: the environmental trigger (gluten), genetic susceptibility, and unusual gut permeability. The only treatment currently available is a strict gluten-free diet. Unfortunately, a majority of patients have difficulty complying with this diet, and the response to therapy is poor. Therefore, alternative treatments are being developed, and new insights into the pathophysiology of celiac disease have led to research into novel therapies. New treatments include engineering gluten-free grains, decreasing intestinal permeability by blockage of the epithelial zonulin receptor, inducing oral tolerance to gluten with a therapeutic vaccine, and degrading immunodominant gliadin peptides using probiotics with endopeptidases or transglutaminase inhibitors. These nondiet-based therapies provide hope for enhanced, lifelong celiac disease management with improved patient compliance and better quality of life.

Current and future role of biomarkers in Crohn's disease risk assessment and treatment.

BACKGROUND: Crohn's disease (CD), a chronic inflammatory bowel disease (IBD), occurs in genetically susceptible individuals who develop aberrant immune responses to endoluminal bacteria. Recurrent inflammation increases the risk of several complications. Despite use of a traditional "step-up" therapy with corticosteroids and immunomodulators, most CD patients eventually require surgery at some time in their disease course. Newer biologic agents have been remarkably effective in controlling severe disease. Thus, "top-down," early aggressive therapy has been proposed to yield better outcomes, especially in complicated disease. However, safety and cost issues mandate the need for careful patient selection. Identification of high-risk candidates who may benefit from aggressive therapy is becoming increasingly relevant. Serologic and genetic markers of CD have great potential in this regard. The aim of this review is to highlight the clinical relevance of these markers for diagnostics and prognostication. METHODS: A current PubMed literature search identified articles regarding the role of biomarkers in IBD diagnosis, severity prediction, and stratification. Studies were also reviewed on the presence of IBD markers in non-IBD diseases. RESULTS: Several IBD seromarkers and genetic markers appear to be associated with complex CD phenotypes. Qualitative and quantitative serum immune reactivity to microbial antigens may be predictive of disease progression and complications. CONCLUSION: The cumulative evidence provided by serologic and genetic testing has the potential to enhance clinical decision-making when formulating individualized IBD therapeutic plans.

Current and future role of serogenomics in ulcerative colitis.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, occurs in genetically susceptible individuals who mount inappropriate immune responses to endoluminal antigens. Serologic and genetic markers have shown great potential for clinical application in Crohn's disease (CD), particularly for prognostication. However, their use is not as well established in UC. The aim of this paper is to highlight the clinical relevance of these markers for diagnostics and prognostication in UC. This review identified studies that cited the use of serum and genetic biomarkers in UC when these biomarkers were used in diagnostic, prognostic, and therapeutic response prediction applications. Several serologic and genetic markers associated with UC were identified, and this review presents and summarizes these data, focusing on the biomarkers' established and emerging diagnostic and prognostic utility. Although more established in CD, the data provided by serologic and genetic testing in UC has the potential to enhance clinical decision making.

Probiotic therapy for irritable bowel syndrome.

The etiology of irritable bowel syndrome (IBS) is thought to be multifactorial, with several factors (including alterations in gut motility, small-bowel bacterial overgrowth, microscopic inflammation, and visceral hypersensitivity) potentially playing a role. Recent studies have suggested that probiotics may be useful in the treatment of IBS. Although the exact mechanism for how probiotics may aid in the reduction of symptoms commonly found in IBS is unknown, the effects of probiotics on alterations in gut bacteria appear to play a part. This review focuses on recent studies examining the role of probiotics in the treatment of IBS.

Mast cells in gastrointestinal disease.

The function of mast cells in allergic inflammatory reactions is well documented in the literature. Mast cells also play an important role in the regulation of gastrointestinal visceral sensitivity and vascular permeability. Several studies have noted an increased number of mast cells in the mucosa of patients with gastrointestinal diseases such as irritable bowel syndrome, mastocytic enterocolitis, and systemic mastocytosis. The role of mast cells in the symptomatology of these and other diseases has only recently been fully appreciated and could provide avenues for new therapeutic opportunities. This paper examines studies that have evaluated the role of mast cells in various gastrointestinal diseases.

The emerging therapeutic role of probiotics in inflammatory bowel disease.

Nonpathogenic bacteria in a genetically susceptible individual play a suggestive role in the pathogenesis of inflammatory bowel disease (IBD). Probiotics are living organisms that exert a protective effect on intestinal mucosa. Although evidence supporting their use for inducing or maintaining remission of IBD remains limited, it may be reasonable to use probiotics as an adjunct to standard therapy for mild-to-moderate disease. Genetically modified probiotics may provide novel delivery methods of therapeutic payloads to inflamed intestinal mucosa. This review focuses on the emerging use of probiotics in the treatment of IBD.