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Systematic Review and Meta-Analysis: Accuracy of Both Gamma Delta+ Intraepithelial Lymphocytes and Coeliac Lymphogram Evaluated by Flow Cytometry for Coeliac Disease Diagnosis.
Fernández-Bañares, F, Carrasco, A, Martín, A, Esteve, M
Nutrients. 2019;(9)
Abstract
UNLABELLED It has been suggested that in doubtful cases of coeliac disease, a high CD3+ T-cell receptor gamma delta+ (TCRγδ+) intraepithelial lymphocyte count increases the likelihood of coeliac disease. AIM: To evaluate the diagnostic accuracy of both an isolated increase of TCRγδ+ cells and a coeliac lymphogram (increase of TCRγδ+ plus decrease of CD3- intraepithelial lymphocytes) evaluated by flow cytometry in the diagnosis of coeliac disease. METHODS The literature search was conducted in MEDLINE and EMBASE. The inclusion criteria were: an article that allows for the construction of a 2 × 2 table of true and false positive and true and false negative values. A diagnostic accuracy test meta-analysis was performed. RESULTS The search provided 49 relevant citations, of which 6 were selected for the analysis, which represented 519 patients and 440 controls. Coeliac lymphogram: The pooled S and Sp were 93% and 98%, without heterogeneity. The area under the SROC curve (AUC) was 0.98 (95% CI, 0.97-0.99). TCRγδ+: Pooled S and Sp were both 95%, with significant heterogeneity. The AUC was 0.97 (95% CI, 0.95-0.98). Conclusions: Both TCRγδ+ count and coeliac lymphogram assessed by flow cytometry in duodenal mucosal samples are associated with a high level of diagnostic accuracy for and against coeliac disease.
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Risk factors associated with intestinal permeability in an adult population: A systematic review.
Leech, B, McIntyre, E, Steel, A, Sibbritt, D
International journal of clinical practice. 2019;(10):e13385
Abstract
BACKGROUND Increased intestinal permeability (IP) involves the loss of integrity between the cells of the small intestine. IP has been suggested to contribute to the pathogenesis and exacerbation of many chronic diseases. Many potential risk factors for IP are proposed in contemporary literature. The purpose of this review is to identify the most significant risk factors for IP. METHODS A systematic search of literature published up until September 2018 in the PubMed, EMBASE, CINAHL, and Scopus databases was conducted. RESULTS A total of 47 articles met the inclusion criteria. Elevated levels of proinflammatory markers, dyslipidaemia, hyperglycaemia, insulin resistance, anthropometric measurements resembling obesity, advanced disease severity, comorbidity and the consumption of a Western-style diet were identified as the strongest risk factors for altered intestinal integrity. The risk of IP increases when coupled with a multiple disease state or combined with other environmental risk factors. Furthermore, many of the identified risk factors such as anthropometric measurements and biomarkers were external from intestinal health and rather resembled a metabolic-like condition. CONCLUSIONS This review identified a number of potential risk factors for IP, ranging from biomarkers to anthropometric measurements, demographics, dietary intake and chronic diseases. These risk factors warrant the attention of clinicians and other healthcare providers to aid the identification of potential patients at risk of altered IP. Further research needs to examine whether the identified risk factors are homogeneous with the diagnosis of IP or whether the disease state influences the association.
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[Translational Research Based on Understanding the Regulatory Mechanisms of in Vivo Behaviors of Fat-soluble Compounds].
Yamanashi, Y
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2019;(12):1485-1494
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Abstract
Several fat-soluble compounds such as cholesterol and fat-soluble vitamins have important physiological activities in the body, and their excess and/or deficiency have been reported to be closely associated with the onset and progression of several conditions such as lifestyle-related diseases. It is important to clarify not only the physiological activities but also in vivo kinetics of fat-soluble compounds to understand their in vivo activity (toxicity). This review introduces our recent (reverse) translational research in a combination of basic and clinical studies to reveal the regulatory mechanisms of in vivo behaviors of fat-soluble compounds and effects of their disruption in humans.
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Beneficial Effects of Probiotic Consumption on the Immune System.
Maldonado Galdeano, C, Cazorla, SI, Lemme Dumit, JM, Vélez, E, Perdigón, G
Annals of nutrition & metabolism. 2019;(2):115-124
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Abstract
BACKGROUND The gastrointestinal tract is one of the most microbiologically active ecosystems that plays a crucial role in the working of the mucosal immune system (MIS). In this ecosystem, the consumed probiotics stimulate the immune system and induce a network of signals mediated by the whole bacteria or their cell wall structure. This review is aimed at describing the immunological mechanisms of probiotics and their beneficial effects on the host. SUMMARY Once administered, oral probiotic bacteria interact with the intestinal epithelial cells (IECs) or immune cells associated with the lamina propria, through Toll-like receptors, and induce the production of different cytokines or chemokines. Macrophage chemoattractant protein 1, produced by the IECs, sends signals to other immune cells leading to the activation of the MIS, characterized by an increase in immunoglobulin A+ cells of the intestine, bronchus and mammary glands, and the activation of T cells. Specifically, probiotics activate regulatory T cells that release IL-10. Interestingly, probiotics reinforce the intestinal barrier by an increase of the mucins, the tight junction proteins and the Goblet and Paneth cells. Another proposed mechanism of probiotics is the modulation of intestinal microbiota by maintaining the balance and suppressing the growth of potential pathogenic bacteria in the gut. Furthermore, it has been demonstrated that long-term probiotics consumption does not affect the intestinal homeostasis. The viability of probiotics is crucial in the interaction with IECs and macrophages favoring, mainly, the innate immune response. Macrophages and Dendritic cells (DCs) play an important role in this immune response without inducing an inflammatory pattern, just a slight increase in the cellularity of the lamina propria. Besides, as part of the machinery that probiotics activate to protect against different pathogens, an increase in the microbicidal activity of peritoneal and spleen macrophages has been reported. In malnutrition models, such as undernourishment and obesity, probiotic was able to increase the intestinal and systemic immune response. Furthermore, probiotics contribute to recover the histology of both the intestine and the thymus damaged in these conditions. Probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. Different mechanisms such as the generation of cytokines from activated pro-T-helper type 1, which favor the production of IgG instead of IgE, have been proposed. Key Messages: Probiotic bacteria, their cell walls or probiotic fermented milk have significant effects on the functionality of the mucosal and systemic immune systems through the activation of multiple immune mechanisms.
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A comprehensive review and update on ulcerative colitis.
Gajendran, M, Loganathan, P, Jimenez, G, Catinella, AP, Ng, N, Umapathy, C, Ziade, N, Hashash, JG
Disease-a-month : DM. 2019;(12):100851
Abstract
Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disorder of the colon that causes continuous mucosal inflammation extending from the rectum to the more proximal colon, with variable extents. UC is characterized by a relapsing and remitting course. UC was first described by Samuel Wilks in 1859 and it is more common than Crohn's disease worldwide. The overall incidence and prevalence of UC is reported to be 1.2-20.3 and 7.6-245 cases per 100,000 persons/year respectively. UC has a bimodal age distribution with an incidence peak in the 2nd or 3rd decades and followed by second peak between 50 and 80 years of age. The key risk factors for UC include genetics, environmental factors, autoimmunity and gut microbiota. The classic presentation of UC include bloody diarrhea with or without mucus, rectal urgency, tenesmus, and variable degrees of abdominal pain that is often relieved by defecation. UC is diagnosed based on the combination of clinical presentation, endoscopic findings, histology, and the absence of alternative diagnoses. In addition to confirming the diagnosis of UC, it is also important to define the extent and severity of inflammation, which aids in the selection of appropriate treatment and for predicting the patient's prognosis. Ileocolonoscopy with biopsy is the only way to make a definitive diagnosis of UC. A pathognomonic finding of UC is the presence of continuous colonic inflammation characterized by erythema, loss of normal vascular pattern, granularity, erosions, friability, bleeding, and ulcerations, with distinct demarcation between inflamed and non-inflamed bowel. Histopathology is the definitive tool in diagnosing UC, assessing the disease severity and identifying intraepithelial neoplasia (dysplasia) or cancer. The classical histological changes in UC include decreased crypt density, crypt architectural distortion, irregular mucosal surface and heavy diffuse transmucosal inflammation, in the absence of genuine granulomas. Abdominal computed tomographic (CT) scanning is the preferred initial radiographic imaging study in UC patients with acute abdominal symptoms. The hallmark CT finding of UC is mural thickening with a mean wall thickness of 8 mm, as opposed to a 2-3 mm mean wall thickness of the normal colon. The Mayo scoring system is a commonly used index to assess disease severity and monitor patients during therapy. The goals of treatment in UC are three fold-improve quality of life, achieve steroid free remission and minimize the risk of cancer. The choice of treatment depends on disease extent, severity and the course of the disease. For proctitis, topical 5-aminosalicylic acid (5-ASA) drugs are used as the first line agents. UC patients with more extensive or severe disease should be treated with a combination of oral and topical 5-ASA drugs +/- corticosteroids to induce remission. Patients with severe UC need to be hospitalized for treatment. The options in these patients include intravenous steroids and if refractory, calcineurin inhibitors (cyclosporine, tacrolimus) or tumor necrosis factor-α antibodies (infliximab) are utilized. Once remission is induced, patients are then continued on appropriate medications to maintain remission. Indications for emergency surgery include refractory toxic megacolon, colonic perforation, or severe colorectal bleeding.
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Association of intestinal permeability with a NUTRIC score in critically ill patients.
Eslamian, G, Ardehali, SH, Vahdat Shariatpanahi, Z
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:1-8
Abstract
OBJECTIVES The aim of this study was to investigate the association of intestinal permeability with the Nutrition Risk in Critically Ill (NUTRIC) score and the modified NUTRIC score (mNUTRIC) in intensive care unit (ICU) hospitalized patients. METHODS One hundred and fifty ICU hospitalized adult patients admitted between October 2017 and April 2018 who stayed for >24 h in the general ICU were enrolled in the study. Nutrition status was estimated using the NUTRIC score, an ICU-specific nutrition risk assessment tool. The NUTRIC score was calculated using the exact same thresholds and point system as developed previously. Admission plasma endotoxin and zonulin concentrations were measured to assess intestinal permeability. RESULTS Median plasma endotoxin and zonulin increased with increasing mNUTRIC and NUTRIC categories in the overall study population and in the glutamine-deficient subgroup. Multivariate binary logistic regression analyses showed a significant association between the plasma endotoxin (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.8-3.52) and zonulin (OR, 1.11; 95% CI, 1.03-1.20) levels with NUTRIC category in the overall population and the glutamine-deficient subgroup. Similar results were obtained when using mNUTRIC. CONCLUSIONS Results from the present study provided evidence that higher plasma endotoxin and zonulin levels are associated with a progressively higher NUTRIC score in critically ill patients.
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Overview in the clinical management of patients with seronegative villous atrophy.
Schiepatti, A, Sanders, DS, Zuffada, M, Luinetti, O, Iraqi, A, Biagi, F
European journal of gastroenterology & hepatology. 2019;(4):409-417
Abstract
Differential diagnosis and management of enteropathies found in the context of seronegative villous atrophy (VA) are still a clinical challenge. Although seronegative coeliac disease may be the most frequent cause of serology-negative VA, other conditions must be taken into account in the differential diagnosis of seronegative VA. The rarity of these enteropathies with frequent overlapping of histological features may result in misclassification of such patients as affected by a seronegative or a refractory form of coeliac disease with consequent inappropriate treatments and long-term morbidity. The aim of this review is to summarize the current knowledge and to provide an evidence base and practical algorithmic approach for the investigation and management of seronegative VA.
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Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial.
Louis-Auguste, J, Besa, E, Zyambo, K, Munkombwe, D, Banda, R, Banda, T, Watson, A, Mayneris-Perxachs, J, Swann, J, Kelly, P
The American journal of clinical nutrition. 2019;(5):1240-1252
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BACKGROUND Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH). OBJECTIVE We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE. METHODS AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes. RESULTS Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 μm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite β-hydroxy-β-methylbutyrate, which was increased by AA supplementation and correlated with VH. CONCLUSIONS In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.
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Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease.
Biolato, M, Manca, F, Marrone, G, Cefalo, C, Racco, S, Miggiano, GA, Valenza, V, Gasbarrini, A, Miele, L, Grieco, A
World journal of gastroenterology. 2019;(4):509-520
Abstract
BACKGROUND In non-alcoholic fatty liver disease (NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis. We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD. AIM: To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet. METHODS The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing (51Cr-EDTA). RESULTS Twenty Caucasian patients, 90% male, median age 43 years, body mass index (BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight (-5.3 ± 4.1 kg, P = 0.003), mean waist circumference (-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase (ALT) -28.3 ± 11.9 IU/L, P = 0.0001; aspartate aminotransferase (AST) -6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after 16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline (mean percentage retention of 51Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet. CONCLUSION Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.
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Taming the Beast: Interplay between Gut Small Molecules and Enteric Pathogens.
Kumar, A, Ellermann, M, Sperandio, V
Infection and immunity. 2019;(9)
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The overuse of antibiotics has led to the evolution of drug-resistant bacteria that are becoming increasingly dangerous to human health. According to the Centers for Disease Control and Prevention, antibiotic-resistant bacteria cause at least 2 million illnesses and 23,000 deaths in the United States annually. Traditionally, antibiotics are bactericidal or bacteriostatic agents that place selective pressure on bacteria, leading to the expansion of antibiotic-resistant strains. In addition, antibiotics that are effective against some pathogens can also exacerbate their pathogenesis and may lead to severe progression of the disease. Therefore, alternative strategies are needed to treat antibiotic-resistant bacterial infections. One novel approach is to target bacterial virulence to prevent or limit pathogen colonization, while also minimizing tissue damage and disease comorbidities in the host. This review focuses on the interactions between enteric pathogens and naturally occurring small molecules in the human gut as potential therapeutic targets for antivirulence strategies. Individual small molecules in the intestines modulate enteric pathogen virulence and subsequent intestinal fitness and colonization. Targeted interruption of pathogen sensing of these small molecules could therefore attenuate their virulence. This review highlights the paths of discovery for new classes of antimicrobials that could potentially mitigate the urgent problem of antibiotic resistance.