The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Nonmalignant Gastrointestinal Diseases.

Esophageal, colorectal, pancreatic, hepatocellular, and gastric cancer together impact millions of patients worldwide each year, with high overall mortality rates, and are increasing in incidence. Additionally, premalignant gastrointestinal diseases, such as Barrett's esophagus and inflammatory bowel disease, are also increasing in incidence. However, involvement of aberrant DNA methylation in these diseases is incompletely understood, especially given recent research advancements in this field. Here, we review knowledge of this epigenetic mechanism in gastrointestinal preneoplasia and neoplasia, considering mechanisms of action, genetic and environmental factors, and 5'-C-phosphate-G-3' island methylator phenotype. We also highlight developments in translational research, focusing on genomic-wide database data, methylation-based biomarkers and diagnostic tests, machine learning, and therapeutic epigenetic strategies.

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

Food insecurity and allergic diseases: A call to collective action.

Food security encompassess the concept of access by all people at all times to enough food for an active, healthy life. Conversely, food insecurity (FI) refers to household-level economic and social conditions of limited or uncertain access to adequate food. FI is a key social determinant of health that can negatively affect nutrition and health outcomes, as it is estimated that 10.2% of the US population meets criteria for FI. Recognizing the impact of FI on our patients and families is critical to promote health equity and optimize health outcomes. This review focuses on FI and allergic disease from the perspective of key multisector stakeholders within the field of allergy and immunology as well as from the larger health care arena, highlighting key resources and initiatives important to patients. Collectively, as specialists in allergy and immunology, and within the medical field more broadly, we must leverage our unique roles as we interface with patients and families and serve as committed advocates for change. Developing innovative strategies to promote health equity can provide a pathway forward for all children, adults, and families to gain access to healthy, nutritious food as part of their routine lifestyle. This is a call to action.

Global Burden of Digestive Diseases: A Systematic Analysis of the Global Burden of Diseases Study, 1990 to 2019.

BACKGROUND & AIMS: This study assessed the worldwide burden of digestive diseases between 1990 and 2019. METHODS: We analyzed data from the Global Burden of Diseases study, covering 18 digestive diseases across 204 countries and territories. Key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), were studied. Linear regression analysis was applied to the natural logarithm of age-standardized outcomes to determine the annual percent change. RESULTS: In 2019, there were 7.32 billion incidents and 2.86 billion prevalent cases of digestive diseases, resulting in 8 million deaths and 277 million DALYs lost. Little to no decrease in global age-standardized incidence and prevalence of digestive diseases was observed between 1990 and 2019, with 95,582 and 35,106 cases per 100,000 individuals in 2019, respectively. The age-standardized death rate was 102 per 100,000 individuals. Digestive diseases accounted for a significant portion of the overall disease burden, with more than one-third of prevalent cases having a digestive etiology. Enteric infections were the primary contributor to incidence, death, and DALYs lost, whereas cirrhosis and other chronic liver diseases had the highest prevalence rate. The burden of digestive diseases was inversely related to the sociodemographic index, with enteric infections being the predominant cause of death in low and low-middle quintiles and colorectal cancer in the high quintile. CONCLUSIONS: Despite significant reductions in deaths and DALYs due to digestive diseases from 1990 to 2019, they remain prevalent. A significant disparity in the burden of digestive diseases exists among countries with different development levels.

Causal relationship between gut microbiota and gastrointestinal diseases: a mendelian randomization study.

BACKGROUND: Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases. METHODS: Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed. RESULTS: The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results. CONCLUSIONS: The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.

Risk of Serious Adverse Gastrointestinal Events with Potassium Binders in Hospitalized Patients: A National Study.

BACKGROUND: Concerns about serious adverse gastrointestinal (GI) events with sodium polystyrene sulfonate (SPS) led to development of two new potassium binders, patiromer and sodium zirconium cyclosilicate (SZC), for treatment of hyperkalemia. OBJECTIVE: To compare risk of intestinal ischemia/thrombosis or other serious GI events associated with SPS, patiromer, or SZC in hospitalized patients. DESIGN: Retrospective cohort study. PARTICIPANTS: National sample of 3,144,960 veterans hospitalized 2016-2022 in the U.S. Department of Veterans Affairs Healthcare System. MAIN MEASURES: Demographics, comorbidities, medications and outcomes were ascertained from the VA Corporate Data Warehouse. Exposures were SPS, patiromer, SZC. Outcomes were 30-day intestinal ischemia/thrombosis, and a composite of intestinal ischemia/thrombosis, peptic ulcer/perforation or bowel resection/ostomy. KEY RESULTS: Potassium binders were used during 39,270 (1.3%) hospitalizations: SPS = 30,040 (1.0%), patiromer = 3,750 (0.1%), and SZC = 5,520 (0.2%). Intestinal ischemia/thrombosis occurred with 106/30,040 (0.4%) SPS, 12/3750 (0.3%) patiromer and 24/5520 (0.4%) SZC, vs. 6998/3,105,650 (0.2%) without potassium binder. Adjusted odds ratios (aOR) were 1.40 [95% CI, 1.16 to 1.69] with SPS, 1.36 [CI, 0.79 to 2.36] with patiromer, and 1.78 [CI, 1.21 to 2.63] with SZC exposures. Composite GI adverse events occurred with 754/30,040 (2.5%) SPS, 96/3750 (2.6%) patiromer, 2.6% SZC, vs. 144/5520 (2.4%) without binder; aOR were 1.00 [CI, 0.94 to 1.08] with SPS, 1.08 [CI, 0.89 to 1.32] with patiromer, and 1.08 [CI, 0.93 to 1.27] with SZC exposures. No statistical difference in intestinal ischemia/thrombosis between each new agent and SPS was seen (p = 0.274 for SPS vs. SZC; p = 0.916 for SPS vs. patiromer). CONCLUSION: Risk of intestinal ischemia/thrombosis or other serious adverse GI events was low and did not differ across three potassium-binding drugs.

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Human cytomegalovirus-related gastrointestinal disease after kidney transplantation: A systematic review.

BACKGROUND: Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID). METHODS: We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs. RESULTS: Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3). CONCLUSIONS: The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.

Genetic evidence for the causal impact of insomnia on gastrointestinal diseases and the mediating effects of adiposity traits.

BACKGROUND AND AIM: Insomnia has been implicated in gastrointestinal diseases (GIs), but the causal effect between insomnia and GIs and underlying mechanisms remain unknown. METHODS: By using the released summary-level data, we conducted a two-step Mendelian randomization (MR) analysis to examine the relationship between insomnia and four GIs and estimate the mediating role of candidate mediators. The first step was to investigate the causal association between insomnia and GIs using univariable MR analysis. The second step was to estimate the mediation proportion of selected mediators in these associations using multivariable MR analysis. Subsequently, results from different datasets were combined using the fixed-effect meta-analysis. RESULTS: Univariable MR analysis provided strong evidence for the causal effects of insomnia on four GIs after Bonferroni correction for multiple comparisons, including peptic ulcer disease (PUD) (odds ratio [OR] = 1.15, 95% interval confidence [CI] = 1.10-1.20, P = 1.83 × 10-9), gastroesophageal reflux (GORD) (OR = 1.19, 95% CI = 1.16-1.22, P = 5.95 × 10-42), irritable bowel syndrome (IBS) (OR = 1.18, 95% CI = 1.15-1.22, P = 8.69 × 10-25), and inflammatory bowel disease (IBD) (OR = 1.09, 95% CI = 1.03-1.05, P = 3.46 × 10-3). In the mediation analysis, body mass index (BMI) and waist-to-hip ratio (WHR) were selected as mediators in the association between insomnia and PUD (BMI: mediation proportion [95% CI]: 13.61% [7.64%-20.70%]; WHR: 8.74% [5.50%-12.44%]) and GORD (BMI: 11.82% [5.94%-18.74%]; WHR: 7.68% [4.73%-11.12%]). CONCLUSIONS: Our findings suggest that genetically instrumented insomnia has causal effects on PUD, GORD, IBS, and IBD, respectively. Adiposity traits partially mediated the associations between insomnia and GIs. Further clinical studies are warranted to evaluate the protective effect of insomnia treatment on GIs.

Prebiotics in the management of pediatric gastrointestinal disorders: Position paper of the ESPGHAN special interest group on gut microbiota and modifications.

Prebiotics are substrates that are selectively utilized by host microorganisms conferring a health benefit. Compared to probiotics there are few studies with prebiotics in children. Most studies have been performed using infant formula supplemented with prebiotics, while add-on prebiotic supplementation as prevention or treatment of childhood gastrointestinal disorders has rarely been reported. The aim of this position paper was to summarize evidence and make recommendations for prebiotic supplementation in children with gastrointestinal diseases. Recommendations made are based on publications up to January 1, 2023. Within the scope of the European Society for Paediatric Gastroenterology Hepatology and Nutrition Special Interest Group on Gut Microbiota and Modifications, as in our previous biotic recommendations, at least two randomized controlled clinical trials were required for recommendation. There are some studies showing benefits of prebiotics on selected outcomes; however, we cannot give any positive recommendations for supplementing prebiotics in children with gastrointestinal disorders.

Air pollutants, genetic susceptibility, and the risk of incident gastrointestinal diseases: A large prospective cohort study.

A comprehensive overview of the associations between air pollution and the risk of gastrointestinal (GI) diseases has been lacking. We aimed to examine the relationships of long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2.5), 2.5-10 µm (PMcoarse), ≤10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with the risk of incident GI diseases, and to explore the interplay between air pollution and genetic susceptibility. A total of 465,703 participants free of GI diseases in the UK Biobank were included at baseline. Land use regression models were employed to calculate the residential air pollutants concentrations. Cox proportional hazard models were used to evaluate the associations of air pollutants with the risk of GI diseases. The dose-response relationships of air pollutants with the risk of GI diseases were evaluated by restricted cubic spline curves. We found that long-term exposure to ambient air pollutants was positively associated with the risk of peptic ulcer (PM2.5 : Q4 vs. Q1: hazard ratio (HR) 1.272, 95% confidence interval (CI) 1.179-1.372, NO2: 1.220, 1.131-1.316, and NOx: 1.277, 1.184-1.376) and chronic gastritis (PM2.5: 1.454, 1.309-1.616, PM10 : 1.232, 1.112-1.366, NO2: 1.456, 1.311-1.617, and NOx: 1.419, 1.280-1.574) after Bonferroni correction. Participants with high genetic risk and high air pollution exposure had the highest risk of peptic ulcer, compared to those with low genetic risk and low air pollution exposure (PM2.5: HR 1.558, 95%CI 1.384-1.754, NO2: 1.762, 1.395-2.227, and NOx: 1.575, 1.403-1.769). However, no significant additive or multiplicative interaction between air pollution and genetic risk was found. In conclusion, long-term exposure to ambient air pollutants was associated with increased risk of peptic ulcer and chronic gastritis.

Medical Comorbidities, Nutritional Markers, and Cardiovascular Risk Markers in Youth With ARFID.

OBJECTIVE: Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition-related medical conditions. Less is known about the medical comorbidity/complication frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC). METHOD: In youth with full/subthreshold ARFID (n = 100; 49% female) and HC (n = 58; 78% female), we assessed self-reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high-sensitive C-reactive protein [hs-CRP]) and nutritional (25[OH] vitamin D, vitamin B12, and folate) markers. RESULTS: Youth with ARFID, compared with HC, were over 10 times as likely to have self-reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2-112.1) and over two times as likely to have self-reported immune-mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1-4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7-10.5) and hs-CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4-27.0) levels. DISCUSSION: Self-reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake.

Gastric emphysema and pneumatosis intestinalis in two common marmosets with duodenal dilation syndrome.

BACKGROUND: Common marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood. CASE PRESENTATION: We report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis. CONCLUSIONS: In both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases.

Gastrointestinal Comorbidities Associated with Atopic Dermatitis-A Narrative Review.

The current understanding of atopic dermatitis (AD) seems to be extending beyond a skin-confined condition frequently associated with allergic comorbidities, as in a number of epidemiological studies, the prevalence rate of a range of illnesses has been determined to be greater in patients with AD, or inversely. In most cases, the reasons for this are vague. A subset of these conditions are gastrointestinal disorders, including food sensitization (FS) and food allergy (FA), eosinophilic esophagitis (EoE) (it is of mixed background, both IgE-dependent and independent), food protein-induced enterocolitis syndrome (FPIES) (it exemplifies an IgE-independent food allergy), Crohn's disease (CD), colitis ulcerosa (CU), celiac disease, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD). In this review, we performed a comprehensive search of the literature using the PubMed database. We addressed the epidemiology of the increased co-occurrence of these diseases with AD and discussed potential causes for this subject. Multiple gastroenterological comorbidities appear to be more common in patients with AD, according to our review. The mechanisms that underlie this phenomenon are largely unknown, highlighting the need for further study in this field.

Advancing Gastrointestinal Health: Curcumin's Efficacy and Nanopreparations.

Curcumin (CCM) is a polyphenol compound extracted from the turmeric rhizome. It has various biological activities, including antibacterial, anti-inflammatory, anti-cancer, and antioxidant. Due to its diverse activities, it is often used by researchers to study the therapeutic effects on various diseases. However, its poor solubility leads to poor bioavailability, and it is necessary to increase the water solubility with the help of carriers to improve the therapeutic effect. Gastrointestinal disease is a major global health problem that continues to affect human health. In this review, we have summarized the possible mechanism and therapeutic effect of CCM in various gastrointestinal diseases, and the improvement in the curative effect of CCM with nanopreparation. Finally, we concluded that there have been many clinical trials of CCM in combination with other drugs for the treatment of gastrointestinal disease, but so far, few have used CCM nanomaterials for treatment. Although in vitro and preclinical experiments have shown that nanopreparations can improve the efficacy of CCM, there are still insufficient studies on the safety of carriers.

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OBJECTIVES: To explore the clinical manifestations, endoscopic findings, histopathological changes, treatment, and prognosis of eosinophilic gastrointestinal disease (EGID) in children, with the aim of enhancing awareness among pediatricians about this condition. METHODS: Data of 267 children with EGID were prospectively collected from January 2019 to July 2022 at Jiangxi Children's Hospital, Hunan Children's Hospital, and Henan Children's Hospital. The age of onset, symptoms, physical signs, laboratory examination results, endoscopic findings, histopathological changes, and treatment outcomes were observed. RESULTS: Among the 267 children with EGID, the majority had mild (164 cases, 61.4%) or moderate (96 cases, 35.6%) clinical severity. The disease occurred at any age, with a higher prevalence observed in school-age children (178 cases). The main symptoms in infants were vomiting and hematemesis, while in toddlers, vomiting and bloody stools were prominent. Abdominal pain and vomiting were the primary symptoms in preschool and school-age children. Nearly half (49.4%) of the affected children showed elevated platelet counts on hematological examination, but there was no significant difference in platelet counts among children with mild, moderate, and severe EGID (P>0.05). Endoscopic findings in EGID children did not reveal significant specificity, and histopathological examination showed no specific structural damage. Among them, 85.0% (227 cases) received acid suppression therapy, 34.5% (92 cases) practiced dietary avoidance, 20.9% (56 cases) received anti-allergic medication, and a small proportion (24 cases, 9.0%) were treated with prednisone. Clinical symptoms were relieved in all patients after treatment, but three cases with peptic ulcers experienced recurrence after drug discontinuation. CONCLUSIONS: Mild and moderate EGID are more common in children, with no specific endoscopic findings. Dietary avoidance, acid suppression therapy, and anti-allergic medication are the main treatment methods. The prognosis of EGID is generally favorable in children.

Eosinophilic Esophagitis: Etiology and Therapy.

Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE.

Urolithin B alleviates Helicobacter pylori-induced inflammation and oxidative stress in mice.

BACKGROUND: Helicobacter pylori is one of the most common chronic bacterial infections. Active eradication of H. pylori infection is rare due to the fact that most infected patients are asymptomatic and the use of large amounts of antibiotics in eradication therapy leads to severe side effects. Urolithin B (UB) is an additional major intestinal metabolite of ellagic acid (EA), which has been shown to possess anti-inflammatory, antioxidant, and antiapoptotic biological activities. Preventing the incidence of H. pylori-related gastric disease and reducing the damage to the host by H. pylori is a current approach to control H. pylori infection. In this study, we explored the effect of UB on H. pylori infection. MATERIALS AND METHODS: The effects of UB on inflammation and oxidative stress induced by H. pylori in vivo and in vitro were investigated by qPCR, ELISA, HE staining, IHC staining, etc. RESULTS: UB reduced the adhesion and colonization of H. pylori and improved H. pylori-induced inflammation and oxidative stress in vivo and in vitro. Moreover, UB had better anti-inflammatory and antioxidant effects than clarithromycin (CLR) and metronidazole (MET). In addition to inhibiting the secretion of CagA, UB reduced tissue damage by H. pylori infection. CONCLUSIONS: UB was effective in improving damage caused by H. pylori.

Genetic and Molecular Contributors in Eosinophilic Esophagitis.

PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is an allergic inflammatory esophageal disorder with a complex underlying genetic and molecular etiology. The interest of the scientific community in EoE has grown considerably over the past three decades, and the understanding of the genetic and molecular mechanisms involved in this disease has greatly increased. RECENT FINDINGS: In this article, we aim to provide both historic aspects and updates on the recent genetic and molecular advances in the understanding of EoE. Although EoE is a relatively newly described disorder, much progress has been made toward identifying the genetic and molecular factors contributing to the disease pathogenesis by a variety of approaches with next-generation sequencing technologies, including genome-wide association study, whole exome sequencing, and bulk and single-cell RNA sequencing. This review highlights the multifaceted impacts of various findings that have shaped the current molecular and genetic landscape of EoE, providing insights that facilitate further understanding of the disease process.

Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study.

OBJECTIVE: To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. BACKGROUND: Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition. METHODS: Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed. RESULTS: Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99-1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99-1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96-1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79-1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00-1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92-0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02-1.29, p = 0.025). However, the results were not significant after multiple testing correction. CONCLUSIONS: We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.