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Effect of Different Modalities of Purgative Preparation on the Diagnostic Yield of Small Bowel Capsule for the Exploration of Suspected Small Bowel Bleeding: A Multicenter Randomized Controlled Trial.
Rahmi, G, Cholet, F, Gaudric, M, Filippi, J, Duburque, C, Bramli, S, Quentin, V, Alavi, Z, Nowak, E, Saurin, JC, et al
The American journal of gastroenterology. 2022;(2):327-335
Abstract
INTRODUCTION The aim of our study was to compare clear liquid diet with 2 different polyethylene glycol (PEG)-based bowel preparation methods regarding diagnostic yield of small bowel capsule endoscopy (SBCE) in patients with suspected small bowel bleeding (SBB). METHODS In this prospective multicenter randomized controlled trial, consecutive patients undergoing SBCE for suspected SBB between September 2010 and February 2016 were considered. Patients were randomly assigned to standard regimen, that is, clear fluids only (prep 1), standard regimen plus 500 mL PEG after SBCE ingestion (prep 2), or standard regimen plus 2 L PEG plus 500 mL PEG after SBCE ingestion (prep 3). The primary outcome was the detection of at least one clinically significant lesion in the small bowel. The quality of small bowel cleansing was assessed. A questionnaire on the clinical tolerance was filled by the patients. RESULTS We analyzed 834 patients. No significant difference was observed for detection of P1 or P2 small bowel lesions between prep1 group (40.5%), prep 2 group (40.2%), and prep 3 group (38.5%). Small bowel cleansing was improved in prep 2 and 3 groups compared with that in prep 1 group. Compliance to the preparation and tolerance was better in prep 2 group than in prep 3 group. DISCUSSION Small bowel purgative before SBCE allowed better quality of cleansing. However, it did not improve diagnostic yield of SBCE for suspected SBB.
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Quantitative prediction of pharmacokinetic properties of drugs in humans: Recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood-brain barrier.
Hashimoto, Y, Michiba, K, Maeda, K, Kusuhara, H
Journal of pharmacological sciences. 2022;(1):142-151
Abstract
Efflux transport systems are essential to suppress the absorption of xenobiotics from the intestinal lumen and protect the critical tissues at the blood-tissue barriers, such as the blood-brain barrier. The function of drug efflux transport is dominated by various transporters. Accumulated clinical evidences have revealed that genetic variations of the transporters, together with coadministered drugs, affect the expression and/or function of transporters and subsequently the pharmacokinetics of substrate drugs. Thus, in the preclinical stage of drug development, quantitative prediction of the impact of efflux transporters as well as that of uptake transporters and metabolic enzymes on the pharmacokinetics of drugs in humans has been performed using various in vitro experimental tools. Various kinds of human-derived cell systems can be applied to the precise prediction of drug transport in humans. Mathematical modeling consisting of each intrinsic metabolic or transport process enables us to understand the disposition of drugs both at the organ level and at the level of the whole body by integrating a variety of experimental results into model parameters. This review focuses on the role of efflux transporters in the intestinal absorption and brain distribution of drugs, in addition to recent advances in predictive tools and methodologies.
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Metabolic liver disease - what's in a name?
Herman, MA
Nature reviews. Endocrinology. 2021;(2):79-80
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Development and Validation of Test for "Leaky Gut" Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults.
Khoshbin, K, Khanna, L, Maselli, D, Atieh, J, Breen-Lyles, M, Arndt, K, Rhoten, D, Dyer, RB, Singh, RJ, Nayar, S, et al
Gastroenterology. 2021;(2):463-475.e13
Abstract
BACKGROUND Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. AIMS The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose. RESULTS Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D. CONCLUSIONS Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.
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Drivers of transcriptional variance in human intestinal epithelial organoids.
Criss, ZK, Bhasin, N, Di Rienzi, SC, Rajan, A, Deans-Fielder, K, Swaminathan, G, Kamyabi, N, Zeng, XL, Doddapaneni, H, Menon, VK, et al
Physiological genomics. 2021;(11):486-508
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Abstract
Human intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the human intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity. RNA-sequencing datasets from 276 experiments performed on 37 human enteroid and colonoid lines from 29 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and gene set enrichment analysis (GSEA) were used to identify differentially expressed genes and enriched pathways. PERMANOVA, Pearson's correlation, and dendrogram analysis of the data originally indicated three tiers of influence of culture methods on transcriptomic variation: substrate (collagen vs. Matrigel) and format (3-D, transwell, and monolayer) had the largest effect; segment of origin (duodenum, jejunum, ileum, colon) and differentiation status had a moderate effect; and patient heterogeneity and specific experimental manipulations (e.g., pathogen infection) had the smallest effect. GSEA identified hundreds of pathways that varied between culture methods, such as IL1 cytokine signaling enriched in transwell versus monolayer cultures and E2F target genes enriched in collagen versus Matrigel cultures. The transcriptional influence of the format was furthermore validated in a synchronized experiment performed with various format-substrate combinations. Surprisingly, large differences in organoid transcriptome were driven by variations in culture methods such as format, whereas experimental manipulations such as infection had modest effects. These results show that common variations in culture conditions can have large effects on intestinal organoids and should be accounted for when designing experiments and comparing results between laboratories. Our data constitute the largest RNA-seq dataset interrogating human intestinal epithelial organoids.
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Small and Large Intestine (II): Inflammatory Bowel Disease, Short Bowel Syndrome, and Malignant Tumors of the Digestive Tract.
Ber, Y, García-Lopez, S, Gargallo-Puyuelo, CJ, Gomollón, F
Nutrients. 2021;(7)
Abstract
The small intestine is key in the digestion and absorption of macro and micronutrients. The large intestine is essential for the absorption of water, to allow adequate defecation, and to harbor intestinal microbiota, for which their nutritional role is as important as it is unknown. This article will describe the causes and consequences of malnutrition in patients with inflammatory bowel diseases, the importance of screening and replacement of micronutrient deficits, and the main indications for enteral and parenteral nutrition in these patients. We will also discuss the causes of short bowel syndrome, a complex entity due to anatomical or functional loss of part of the small bowel, which can cause insufficient absorption of liquid, electrolytes, and nutrients and lead to complex management. Finally, we will review the causes, consequences, and management of malnutrition in patients with malignant and benign digestive tumors, including neuroendocrine tumors (present not only in the intestine but also in the pancreas).
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Assessment of small-intestine permeability in healthy Nigerian children is altered by urinary volume and voiding status.
Afolami, I, Samuel, FO, Mwangi, M, Oderinde, M, Diepeveen-de Bruin, M, Melse-Boonstra, A
PloS one. 2021;(9):e0253436
Abstract
OBJECTIVE This study aimed to uncover the effect of voided urinary volume on small intestine permeability ratios in healthy children. METHODS We assessed small intestine permeability in 155 apparently healthy children, aged 3-5 years old, without any visible symptoms of disease, in a rural, malaria-endemic setting in Nigeria, using a multi-sugar test solution, comprising lactulose, sucrose, mannitol, and rhamnose. Children were categorized into low urinary volume (LV) and high urinary volume (HV), based on the volume of urine voided per kg body weight per hour. LV children voided less than 25th percentile of the total population, while HV children voided greater than 75th percentile of the total population. Urinary volume excreted over a 90-minute period after administration of the test solution was measured, and differences in sugar ratios were compared between children with high (HV) and low urinary volumes (LV), as well as between children who voided (VC) or who were not able to void (NVC) before administration of the test solution. RESULTS Urinary mannitol and rhamnose recovery were 44% (p = 0.002) and 77% (p<0.001) higher in HV children compared to LV children respectively, while urinary lactulose recovery was 34% lower (p = 0.071). There was no difference in urinary sucrose recovery between groups (p = 0.74). Lactulose-mannitol ratio, lactulose-rhamnose ratio and sucrose-rhamnose ratio were all significantly higher in children in the LV group compared to children in the HV group (p<0.001). In a multiple regression analysis, urinary volume and voiding status combined, explained 13%, 23% and 7% of the variation observed in lactulose-mannitol, lactulose-rhamnose and sucrose-rhamnose ratios, respectively. CONCLUSION Sugar permeability ratios vary significantly with total urinary volume in multi-sugar small-intestine permeability tests. Voiding status before sugar administration appears to influence lactulose recovery, lactulose-rhamnose and sucrose-rhamnose ratios independently of total urinary volume. Evidence from this study suggests the need to take urinary volume into account when conducting multi-sugar small-intestine permeability tests.
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The Use of a PEG/Ascorbate Booster Following Standard Bowel Preparation Improves Visualization for Capsule Endoscopy in a Randomized, Controlled Study.
Mascarenhas-Saraiva, MJ, Oliveira, E, Mascarenhas-Saraiva, MN
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2021;(5):437-442
Abstract
BACKGROUND/AIMS: The increasing use of capsule endoscopy (CE) to examine the gastrointestinal tract highlights the need to establish intestinal preparations that ensure optimal visualization while maximizing patient adherence. Thus, we assessed whether bowel preparation involving dietary restriction and a booster regimen produces adequate CE visualization in a real-world clinical setting. METHODS We conducted a randomized, double-blind, prospective study of CE procedures at 2 tertiary-care centers. Patients were allocated to 3 groups: group 1 followed a clear liquid diet and fasting-based bowel preparation for the exploration (n = 55); group 2 followed the same procedure as group 1 and then ingested 1 L of a polyethylene glycol (PEG)/ascorbic acid booster solution when the capsule reached the small intestine (n = 55); and group 3 followed the same procedure but ingesting only 0.5 L of the booster solution (n = 56). The quality of visualization and the average gastric, orocecal and small-bowel transit times were evaluated. RESULTS A total of 166 patients participated in the study. Significantly higher quality of visualization (Park score) was obtained in group 3 (2.28 ± 0.59) than in group 1 (1.84 ± 0.54, P < .001), while there were no significant differences in the average gastric (range: 36.58- 48.32 min, P = .277), orocecal (range: 322.58-289.45 min, P = .072), and small-bowel transit time (range: 280.71-249.95 min, P = .286) between the 3 groups. CONCLUSIONS Following a clear liquid diet and fasting-based bowel preparation for CE exploration, administering a booster solution of PEG/ascorbic acid after the capsule had reached the small intestine improves mucosal visualization and cleansing without affecting capsule transit times.
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Small Intestinal Bacterial Overgrowth as Potential Therapeutic Target in Parkinson's Disease.
Dănău, A, Dumitrescu, L, Lefter, A, Tulbă, D, Popescu, BO
International journal of molecular sciences. 2021;(21)
Abstract
Increasing evidence suggests that the gut microbiota and the brain are closely connected via the so-called gut-brain axis. Small intestinal bacterial overgrowth (SIBO) is a gut dysbiosis in which the small intestine is abundantly colonized by bacteria that are typically found in the colon. Though not a disease, it may result in intestinal symptoms caused by the accumulation of microbial gases in the intestine. Intestinal inflammation, malabsorption and vitamin imbalances may also develop. SIBO can be eradicated by one or several courses of antibiotics but reappears if the predisposing condition persists. Parkinson's disease (PD) is a common neurodegenerative proteinopathy for which disease modifying interventions are not available. Sporadic forms may start in the gut years before the development of clinical features. Increased gastrointestinal transit time is present in most people with PD early during the course of the disease, predisposing to gut dysbiosis, including SIBO. The role that gut dysbiosis may play in the etiopathogenesis of PD is not fully understood yet. Here, we discuss the possibility that SIBO could contribute to the progression of PD, by promoting or preventing neurodegeneration, thus being a potential target for treatments aiming at slowing down the progression of PD. The direct symptomatic impact of SIBO and its impact on symptomatic medication are also briefly discussed.
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Small Intestinal Bacterial Overgrowth: How to Diagnose and Treat (and Then Treat Again).
Ginnebaugh, B, Chey, WD, Saad, R
Gastroenterology clinics of North America. 2020;(3):571-587
Abstract
Small intestinal bacterial overgrowth (SIBO) is a condition with presentation that can vary from asymptomatic to steatorrhea and malnutrition. Small bowel aspiration and culture is the current gold standard of diagnosis; however, this is invasive and is not without risk to the patient. Breath testing is a noninvasive and less expensive alternative method; however, it lacks diagnostic sensitivity and specificity. Novel diagnostic methods being studied include gas-sensing capsules. The mainstay of treatment is antibiotics; alternative therapies include herbal medications, dietary modifications, and prokinetic agents. Further investigation into less invasive and less harmful diagnostic methods and treatment options is warranted.