The role of ncRNA regulatory mechanisms in diseases-case on gestational diabetes.

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not have the potential to encode proteins. Meanwhile, they can occupy a significant portion of the human genome and participate in gene expression regulation through various mechanisms. Gestational diabetes mellitus (GDM) is a pathologic condition of carbohydrate intolerance that begins or is first detected during pregnancy, making it one of the most common pregnancy complications. Although the exact pathogenesis of GDM remains unclear, several recent studies have shown that ncRNAs play a crucial regulatory role in GDM. Herein, we present a comprehensive review on the multiple mechanisms of ncRNAs in GDM along with their potential role as biomarkers. In addition, we investigate the contribution of deep learning-based models in discovering disease-specific ncRNA biomarkers and elucidate the underlying mechanisms of ncRNA. This might assist community-wide efforts to obtain insights into the regulatory mechanisms of ncRNAs in disease and guide a novel approach for early diagnosis and treatment of disease.

Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models.

Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.

Fructose malabsorption and fructan malabsorption are associated in patients with irritable bowel syndrome.

BACKGROUND: Food malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT). METHODS: We retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm. RESULTS: Of 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate. CONCLUSIONS: Our results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings.

Coexisting Th1 and Th2 cytokines in patients with collagenous gastritis and implications for its pathogenesis.

OBJECTIVES: Collagenous gastritis (CG) is a rare cause of refractory dyspepsia and anemia that frequently affects children and young adults and whose histological hallmark is chronic mucosal inflammation with a subepithelial collagen band. The etiology remains obscure, and no established treatments exist. We investigated the pathogenesis of CG by determining the expression profiles of genes related to immunity and inflammation in index biopsies. METHODS: Gastric biopsies from 10 newly diagnosed patients with CG were evaluated using the NanoString nCounter assay. Gastric biopsies from 14 normal individuals served as controls. The gene expression ratios for CG versus controls were determined in pooled samples and confirmed in individual samples by quantitative reverse transcription polymerase chain reaction. The results were compared with previously reported expression data from a cohort of patients with collagenous colitis, a colonic disorder with similar morphology, including subepithelial collagen band. RESULTS: CG biopsies featured enhanced expression of key genes encoding both Th1 (IFNγ, TNF-α, IL-2, IL-10, IL-12A, IL-12B, and IL-18) and Th2 cytokines (IL-3, IL-4, IL-5, IL-6, and IL-13). In contrast, biopsies from patients with CC exhibited upregulated Th1 cytokines only. CONCLUSIONS: We show in this first published gene expression profiling study that CG involves simultaneous upregulation of Th1 and Th2 cytokines. This finding is unique, contrasting with other types of chronic gastritis as well as with collagenous colitis, which shares the presence of a collagen band. Involvement of Th2 immunity in CG would support further investigation of potential dietary, environmental, or allergic factors to guide future therapeutic trials.

Case Report of 11 Years of Severe Malabsorption, Muscular Atrophy, Seizures, and Immunodeficiency Resolved After Proximal Intercessory Prayer.

We present the case of 11 years of severe malabsorption, muscular atrophy, seizures, and immunodeficiency resolved after proximal intercessory prayer (PIP). A male infant suffered from severe abdominal pain and impaired development with the introduction of solid food at age five months. The patient had previously appeared healthy, having been born to term and breastfed. Neocate and total parenteral nutrition (TPN) were prescribed, and the former was removed due to abdominal pain and diarrhea. Ultimately, the patient became completely dependent on TPN. It was concluded that he suffered from chronic, idiopathic, severe malabsorption. Development of neutropenia, hypogamma-globulinemia, and hypotonia was recorded. Medical records document atrophy and progressive deterioration of muscular symptoms. At five years of age, frontal lobe epilepsy was detected. Over the course of the disease, several genetic tests were performed. Doctors tried unsuccessfully to diagnose an underlying condition, with various mitochondriopathies and Shwachman-Diamond syndrome suggested as possible causes, but no prognosis of recovery was given. Eleven years following the initial presentation of symptoms, proximal intercessory prayer (PIP) was administered in a single session. The patient reported no unusual sensations during prayer. However, oral feedings were immediately tolerated without discomfort from that time onward. Post-PIP medical records indicate discontinuation of TPN, seizures, and seizure medications. Progressive improvement in the hematological disorders, BMI, and muscular symptoms was also observed. The present case report describes a novel association between PIP and the lasting resolution of multiple symptoms likely related to a genetic disorder. The results inform ongoing discussions about faith-based practices in health care and suggest the need for additional studies of PIP on health outcomes.

[Analysis of a child with Microvillus inclusion disease due to variants of MYO5B gene and a literature review].

OBJECTIVE: To explore the clinical and genetic characteristics of a neonate with Microvillus inclusion disease (MVID). METHODS: A neonate with MVID admitted to the First Affiliated Hospital of Zhengzhou University in May 2019 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA). A literature was also carried out to summarize the clinical and genetic characteristics of MVID. RESULTS: The prematurely born neonate had presented with unexplained refractory diarrhea and metabolic acidosis. Active symptomatic treatment was ineffective, and the child had died at 2 months old. WES revealed that he had harbored compound heterozygous variants of the MYO5B gene, namely c.1591C>T (p.R531W) and deletion of exon 9. Sanger sequencing showed that the R531W variant was inherited form his father, and MLPA confirmed that the exon 9 deletion was inherited from his mother. Seven children with MVID were reported in China, of which one was lost during follow-up and six had deceased. One hundred eighty eight patients were reported worldwide and only one was cured. The clinical features of MVID had included refractory diarrhea, metabolic acidosis and poor prognosis. CONCLUSION: The child was diagnosed with MVID due to the compound heterozygous variants of the MYO5B gene, which has provided a basis for genetic counseling and prenatal diagnosis.

[Genetics of sucrose metabolism disorders in different population groups].

The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology. The aim of the study was to systematize the data on the role of the sucrase-isomaltase gene (SI) in regulating sucrose metabolism and the contribution of SI mutations to the prevalence of sucrose malabsorption disorders (sucrase-isomaltase deficiency, SID) and certain forms of enterological pathology in different population groups. Material and methods. A review of the peer-reviewed scientific literature, mainly in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) and eLibrary (https://elibrary.ru), was conducted using key words: carbohydrate malabsorption, sucrase, sucrase-isomaltase deficiency, sucrase-isomaltase SI gene. The search depth was not specified, but particular attention was paid to recent publications. The gnomAD database (https://www.ncbi.nlm. nih.gov/snp/rs781470490) was also used. Results. According to the review results, 37 out of 150 known SI gene mutations have been confirmed to contribute to reduced sucrase activity or restricted sucrase production. The prevalence of point mutations in the SI gene is estimated at 0.0006%, but carrier rates of the SI delAG deletion (rs781470490), manifested as homozygosity in SID, are very high (5-21%) in indigenous populations of Arctic regions in East Asia and America. Medicalgenetic research methods improve the accuracy of differential diagnosis of primary and secondary SID and other forms of disaccharide and polysaccharide malabsorption. The formation of databases on the prevalence of genetic determinants of sucrase-isomaltase insufficiency is a promising way to refine the epidemiology of SID. There is an increased (0.2-2.3%) risk of clinical manifestations of SID in homozygous carriers of the SI delAG mutation in the Chukotka, Kamchatka, and Northern Priochotye populations. Verification of reports on a less pronounced tendency to lipid metabolism disorders in SI delAG carriers compared with the control group is recommended. Conclusion. Manifestations of mutant SI variants in the phenotype are associated with the presence of accompanying carbohydrate malabsorption variants and specific gut microbiota. The SI 15Phe variant (rs9290264) may contribute to the development of irritable bowel syndrome.

Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management.

The concept of small intestinal bacterial overgrowth (SIBO) arose in the context of maldigestion and malabsorption among patients with obvious risk factors that permitted the small bowel to be colonized by potentially injurious colonic microbiota. Such colonization resulted in clinical signs, symptoms, and laboratory abnormalities that were explicable within a coherent pathophysiological framework. Coincident with advances in medical science, diagnostic testing evolved from small bowel culture to breath tests and on to next-generation, culture-independent microbial analytics. The advent and ready availability of breath tests generated a dramatic expansion in both the rate of diagnosis of SIBO and the range of associated gastrointestinal and nongastrointestinal clinical scenarios. However, issues with the specificity of these same breath tests have clouded their interpretation and aroused some skepticism regarding the role of SIBO in this expanded clinical repertoire. Furthermore, the pathophysiological plausibility that underpins SIBO as a cause of maldigestion/malabsorption is lacking in regard to its purported role in irritable bowel syndrome, for example. One hopes that the application of an ever-expanding armamentarium of modern molecular microbiology to the human small intestinal microbiome in both health and disease will ultimately resolve this impasse and provide an objective basis for the diagnosis of SIBO.

Long-term Gastrointestinal Sequelae Following COVID-19: A Prospective Follow-up Cohort Study.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) is associated with long-term gastrointestinal sequelae; however, prospective longitudinal data are sparse. We prospectively studied the frequency, spectrum, and risk factors of post infection functional gastrointestinal disorders/disorders of gut-brain interaction (PI-FGID/DGBI) after COVID-19. METHODS: Three hundred twenty cases with COVID-19 and 2 control groups, group A, 320 healthy spouses/family controls, and group B, 280 healthy COVID serology-negative controls, were prospectively followed up at 1, 3, and 6 months by using validated Rome IV criteria to evaluate the frequency of PI-FGID/DGBI. RESULTS: Of 320 cases, at 1 month 36 (11.3%) developed FGID symptoms. Persistent symptoms were noted in 27 (8.4%) at 3 months and in 21 (6.6%) at 6 months. At 3 months, 8 (2.5%) had irritable bowel syndrome, 7 (2.2%) had functional diarrhea, 6 (1.9%) had functional dyspepsia, 3 (0.9%) had functional constipation, 2 (0.6%) had functional dyspepsia-IBS overlap, and 1 (0.3%) had functional abdominal bloating/distention. Among symptomatic individuals at 3 months, 8 (29.6%) were positive for isolated carbohydrate malabsorption, 1 (3.7%) was positive for post infection malabsorption syndrome, and 1 (3.7%) was positive for intestinal methanogen overgrowth. None of the healthy controls developed FGID up to 6 months of follow-up (P < .01). Predictive factors at 3 and 6 months were severity of infection (P < .01) and presence of gastrointestinal symptoms at the time of infection (P < .01). CONCLUSIONS: COVID-19 led to significantly higher number of new onset PI-FGID/DGBI compared with healthy controls at 3 and 6 months of follow-up. If further investigated, some patients can be diagnosed with underlying malabsorption.

Nonceliac gluten sensitivity.

PURPOSE OF REVIEW: To describe recent advances on nonceliac gluten sensitivity (NCGS), a recently described disorder characterized by variable symptoms and frequent irritable bowel syndrome (IBS)-like manifestations. RECENT FINDINGS: The recent description of disease-triggering wheat components other than gluten, such as fructans and amylase-trypsin inhibitors (ATIs), definitely suggests that nonceliac wheat sensitivity (NCWS) is a better 'umbrella' terminology than NCGS. Self-reported NCWS is very common worldwide, particularly in patients seen at the gastroenterology clinic, but many of these diagnoses are not confirmed by standard clinical criteria. A biomarker of NCWS is still lacking, however, subtle histological features at the small intestinal biopsy may facilitate diagnosis. Treatment of NCWS is based on the gluten-free diet (GFD). The GFD has proven to be an effective treatment of a significant proportion of NCWS-related IBS patients. Dietary therapies for IBS, including the GFD, should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Pioneer studies are under way to test the therapeutic efficacy of supplemental gluten-digesting enzyme preparations in patients with NCWS. SUMMARY: Recent studies highlight interesting pathophysiological and clinical features of NCWS. Many questions remain, however, unanswered, such as the epidemiology, a biomarker(s), and the natural history of this clinical entity.

Dietary advice for patients with bowel-related conditions and malabsorption.

PURPOSE: To explain the pathophysiology of kidney stone formation and appropriate dietary recommendations in inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) and after bariatric surgery, focusing on the current literature. METHODS: A narrative review methodology was performed. A literature search was conducted using PubMed, MEDLINE, and Google Scholar. Studies on the relationship between IBD or bariatric surgery and the risk of kidney stone formation were included. RESULTS: Dietary composition has a critical role in urinary stone formation. Nutritional factors such as fluid intake, dietary protein, carbohydrates, oxalate, and calcium contribute to the risk of stone formation. Bowel-related malabsorptive conditions (IBD, after bariatric surgery, etc.) are associated with an increased risk of kidney stone formation due to metabolic and physiological changes such as hyperoxaluria, hypocitraturia, and decreased fluid intake or absorption. While the risk is lower in restrictive bariatric surgeries, the risk of kidney stone formation increases, especially after malabsorptive procedures. Dietary recommendations for these patients could profit alleviate urinary changes and reduce the risk of kidney stones. CONCLUSION: Bowel-related malabsorptive conditions such as IBD and bariatric surgery are associated with an increased risk of kidney stones. Appropriate dietary recommendations can improve urinary metabolic changes and reduce kidney stone formation and the possibility of stone-related surgery.

Biomarkers for Bile Acid Malabsorption in Diarrhea-predominant Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. METHODS: Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75 Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. RESULTS: The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86 ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97 pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). CONCLUSIONS: The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.

Intestinal Disaccharidase Deficiency in Adults: Evaluation and Treatment.

PURPOSE OF REVIEW: Disaccharidase deficiency in adults causes carbohydrate malabsorption, resulting in symptoms which significantly overlap with irritable bowel syndrome (IBS). This article discusses the diagnosis and treatment of disaccharidase deficiency within the context of recent literature. RECENT FINDINGS: Disaccharidase deficiency in adults is more common than previously thought, which includes lactase, sucrase, maltase and isomaltase enzymes. Deficiency in disaccharidases, which are produced by the intestinal brush border, will interfere with the breakdown and absorption of carbohydrates and may result in abdominal pain, gas, bloating and diarrhea. Patients deficient in all 4 disaccharidases are known as having "pan-disaccharidase" deficiency, which has a distinct phenotype with more reported weight loss than patients deficient in one enzyme. IBS patients who do not respond to low FODMAP dietary restriction may have undiagnosed disaccharidase deficiency and may benefit from testing. Diagnostic testing methods are limited to duodenal biopsies, which is the gold standard, and breath testing. Dietary restriction and enzyme replacement therapy have been shown to be effective treatments in these patients. Disaccharidase deficiency is an underdiagnosed condition in adults with chronic GI symptoms. Patients who do not respond to traditional treatment strategies for DBGI may benefit from testing for disaccharidase deficiency. Further studies delineating the distinctions between disaccharidase deficient patients and those with other motility disorders are needed.

Clinicopathologic Features of IDEDNIK (MEDNIK) Syndrome in a Term Infant: Histopathologic Features of the Gastrointestinal Tract and Report of a Novel AP1S1 Variant.

Inherited syndromes of congenital enteropathy are rare, with many genetic causes described. Mutations of the AP1S1 gene results in the syndrome of intellectual disability, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma (IDEDNIK, formerly in the medical literature as MEDNIK). The clinicopathologic features of the enteropathy in IDEDNIK syndrome have not been fully explored. We describe a female infant who presented with metabolic acidosis, lethargy, and 14 watery stools per day. In the intensive care unit she required parenteral nutrition. She was found to have a novel homozygous pathogenic variant in the AP1S1 gene c.186T>G (p.Y62*). Esophagogastroduodenoscopy and colonoscopy at 6 months of age were grossly normal. However, histologic sections of the duodenum showed mild villous blunting and enterocytes with cytoplasmic vacuoles. CD10 immunostaining highlighted the disrupted brush border. MOC31 immunostaining was wild-type with a membranous pattern of expression. Electron microscopy of the duodenum showed scattered enterocytes cells with shortened and disrupted apical microvilli. Although there is a mixed gap diarrhea and disrupted brush border, there are no significant inclusions typical of microvillus inclusion disease, nor tufted enterocytes typical of tufting enteropathy, making the clinical and histopathologic features for this syndrome unique.

Collagenous Gastritis Is an Underdiagnosed Cause of Anemia and Abdominal Pain: Systematic Scoping Review.

BACKGROUND: Collagenous gastritis (CG) is a rare disease characterized by infiltration of the lamina propria with mononuclear cells and subepithelial deposition of collagen. Due to its nonspecific presentation, it is often misdiagnosed. The clinical characteristics, endoscopic, and histopathologic features, and treatment outcomes of CG have not been well defined. AIMS: We aim to summarize the existing evidence of CG. METHODS: According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with keywords including "collagenous gastritis" and "microscopic gastritis" from the inception of these databases to August 20, 2022. RESULTS: 76 Articles, including nine observational studies, and 67 case reports and series were included. There were 86 cases of collagenous colitis in the final analysis. Most patients presented with anemia (61.4%), followed by abdominal discomfort (60.5%), diarrhea (25.3%), and nausea/vomiting (23.0%). While 60.2% had gastric nodularity on endoscopy, erythema or erosions (26.1%) were also common, as well as normal findings (12.5%). 65.9% of histopathologic findings included subepithelial collagen bands, and 37.5% had mucosal inflammatory infiltrates. Common treatments employed were iron supplementation (42%), followed by PPI (30.7%), prednisone (9.1%), and budesonide (6.8%). Clinical improvement was seen in 64.2%. CONCLUSION: This systematic review summarizes the clinical characteristics of CG. Further studies to establish clear diagnostic criteria and identify effective treatment modalities of this less-recognized entity are needed.

Postoperative Relapse Prediction in Patients With Ewing Sarcoma Using Computed Tomography-Based Radiomics Models Covering Tumor Per Se and Peritumoral Signatures.

OBJECTIVE: We aimed to develop and validate a computed tomography (CT)-based radiomics model for early relapse prediction in patients with Ewing sarcoma (ES). METHODS: We recruited 104 patients in this study. Tumor areas and areas with a tumor expansion of 3 mm were used as regions of interest for radiomics analysis. Six different models were constructed: Pre-CT, CT enhancement (CTE), Pre-CT +3 mm , CTE +3 mm , Pre-CT and CTE combined (ComB), and Pre-CT +3 mm and CTE +3 mm combined (ComB +3 mm ). All 3 classifiers used a grid search with 5-fold cross-validation to identify their optimal parameters, followed by repeat 5-fold cross-validation to evaluate the model performance based on these parameters. The average performance of the 5-fold cross-validation and the best one-fold performance of each model were evaluated. The AUC (area under the receiver operating characteristic curve) and accuracy were calculated to evaluate the models. RESULTS: The 6 radiomics models performed well in predicting relapse in patients with ES using the 3 classifiers; the ComB and ComB +3 mm models performed better than the other models (AUC -best : 0.820-0.922/0.823-0.833 and 0.799-0.873/0.759-0.880 in the training and validation cohorts, respectively). Although the Pre-CT +3 mm , CTE +3 mm, and ComB +3 mm models covering tumor per se and peritumoral CT features preoperatively forecasted ES relapse, the model was not significantly improved. CONCLUSIONS: The radiomics model performed well for early recurrence prediction in patients with ES, and the ComB and ComB +3 mm models may be superior to the other models.

The challenge of personalized cell biology: The example of microvillus inclusion disease.

Whole exome sequencing now provides a tool for rapid analysis of patients manifesting congenital diseases. Congenital diarrheal diseases provide a critical example of the challenges of combining identification of genetic mutations responsible for disease with characterization of the cell biological and cell physiological deficits observed in patients. Recent studies exploring the cellular events associated with loss of functional Myosin 5B (MYO5B) have demonstrated the importance of cell biological and physiological analyses to provide a greater understanding of the implications of pathological mutations. Development of enteroids derived from biopsies of patients with complex congenital diarrheal diseases provides a critical resource for evaluation of the cell biological impact of specific monogenic mutations on enterocyte function. The ability to identify putative causative mutations for congenital disease now provides an opportunity to coordinate the efforts of physicians and cell biologists in an effort to provide patients with personalized cell biology analysis to improve patient diagnosis and treatment.

Collagenous Gastritis: Characteristics and Response to Topical Budesonide.

BACKGROUND AND AIMS: Collagenous gastritis (CG) is a rare disorder characterized by subepithelial collagen deposition in the stomach. Standard medications have been only moderately successful in treating CG. We report results of a large, retrospective, open-label noncontrolled study of topical budesonide for CG, with an aim of establishing an alternative therapy for the disease. METHODS: We identified patients treated for CG at Mayo Clinic (2000-2017) with topically targeted budesonide (TTB) in 2 formulations: open-capsule budesonide or compounded immediate-release budesonide capsule. Demographic, clinical, biochemical, and histologic variables were assessed for all patients before and after treatment. RESULTS: We identified 64 patients with CG (50 adults, 14 children). Most were female (68%), mean age was 41 ± 22.8 years, and body mass index was 23.1 ± 5.9 kg/m2. In most pediatric patients, CG presented with abdominal pain and anemia; in adults, CG presented more often with weight loss (P < .001). Collagenous sprue or colitis were more common in patients >50 years of age (83%) vs those 19-50 years of age (27%) or <19 years of age (50%) (P < .001). Of the patients treated with TTB, 89% had a clinical response to TTB (42% complete, 46% partial), and 88% had a histologic response (53% complete, 33% partial). CONCLUSIONS: Adults and children with CG have a wide variety of symptoms, and notably, TTB therapy produced clinical and histologic improvement after other therapy had failed.

Matriptase drives early-onset intestinal failure in a mouse model of congenital tufting enteropathy.

Syndromic congenital tufting enteropathy (CTE) is a life-threatening recessive human genetic disorder that is caused by mutations in SPINT2, encoding the protease inhibitor HAI-2, and is characterized by severe intestinal dysfunction. We recently reported the generation of a Spint2-deficient mouse model of CTE. Here, we show that the CTE-associated early-onset intestinal failure and lethality of Spint2-deficient mice is caused by unchecked activity of the serine protease matriptase. Macroscopic and histological defects observed in the absence of HAI-2, including villous atrophy, luminal bleeding, loss of mucin-producing goblet cells, loss of defined crypt architecture and the resulting acute inflammatory response in the large intestine, were all prevented by intestinal-specific inactivation of the St14 gene encoding matriptase. The CTE-associated loss of the cell junctional proteins EpCAM and claudin 7 was also prevented. As a result, inactivation of intestinal matriptase allowed Spint2-deficient mice to gain weight after birth and dramatically increased their lifespan. These data implicate matriptase as a causative agent in the development of CTE and may provide a new target for the treatment of CTE in individuals carrying SPINT2 mutations.This article has an associated 'The people behind the papers' interview.

Fructose malabsorption: causes, diagnosis and treatment.

This review intends to act as an overview of fructose malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, irritable bowel syndrome (IBS) and infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients' experiences either constipation (IBS-C) or diarrhoea (IBS-D). FM has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM's relationship with small intestinal bacterial overgrowth. It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, monosaccharides and polyols diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurately diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.