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Low-FODMAP vs regular rye bread in irritable bowel syndrome: Randomized SmartPill® study.
Pirkola, L, Laatikainen, R, Loponen, J, Hongisto, SM, Hillilä, M, Nuora, A, Yang, B, Linderborg, KM, Freese, R
World journal of gastroenterology. 2018;(11):1259-1268
Abstract
AIM: To compare the effects of regular vs low-FODMAP rye bread on irritable bowel syndrome (IBS) symptoms and to study gastrointestinal conditions with SmartPill®. METHODS Our aim was to evaluate if rye bread low in FODMAPs would cause reduced hydrogen excretion, lower intraluminal pressure, higher colonic pH, different transit times, and fewer IBS symptoms than regular rye bread. The study was a randomized, double-blind, controlled cross-over meal study. Female IBS patients (n = 7) ate study breads at three consecutive meals during one day. The diet was similar for both study periods except for the FODMAP content of the bread consumed during the study day. Intraluminal pH, transit time, and pressure were measured by SmartPill, an indigestible motility capsule. RESULTS Hydrogen excretion (a marker of colonic fermentation) expressed as area under the curve (AUC)(0-630 min) was [median (range)] 6300 (1785-10800) ppm∙min for low-FODMAP rye bread and 10 635 (4215-13080) ppm∙min for regular bread (P = 0.028). Mean scores of gastrointestinal symptoms showed no statistically significant differences but suggested less flatulence after low-FODMAP bread consumption (P = 0.063). Intraluminal pressure correlated significantly with total symptom score after regular rye bread (ρ = 0.786, P = 0.036) and nearly significantly after low-FODMAP bread consumption (ρ = 0.75, P = 0.052). We found no differences in pH, pressure, or transit times between the breads. Gastric residence of SmartPill was slower than expected. SmartPill left the stomach in less than 5 h only during one measurement (out of 14 measurements in total) and therefore did not follow on par with the rye bread bolus. CONCLUSION Low-FODMAP rye bread reduced colonic fermentation vs regular rye bread. No difference was found in median values of intraluminal conditions of the gastrointestinal tract.
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Can coffee or chewing gum decrease transit times in Colon capsule endoscopy? A randomized controlled trial.
Buijs, MM, Kobaek-Larsen, M, Kaalby, L, Baatrup, G
BMC gastroenterology. 2018;(1):95
Abstract
BACKGROUND A high rate of complete colon capsule endoscopy (CCE) investigations is required for a more widespread use of CCE. The objective of this study was to assess if coffee or chewing gum can increase excretion of the colon capsule within battery life time (excretion rate). METHODS One hundred eighty six screening participants with a positive immunochemical fecal occult blood test were included in this single-centre randomized controlled trial with blinding of the investigators to the randomization. Participants received instant coffee, chewing gum or nothing in addition to the standard bowel preparation. RESULTS The intention was to include 57 participants in the coffee group, 61 in the chewing gum group and 60 in the control group, on 8 participants data were missing. A total of 165 participants were included in a per protocol analysis. Exclusion was due to not receiving the allocated intervention (8 coffee, 4 chewing gum) and technical failure of the capsule (1 coffee). The excretion rate was 58% in the coffee group (n = 48), 63% in the chewing gum group (n = 57) and 55% in the control group (n = 60, p > 0.2). Transit times were similar in all groups. The excretion rate was low in participants who had transit times over 10 h (14%). A strong correlation was found between adequate cleansing and excretion of the capsule. There were no serious adverse events related to the interventions or CCE investigations. CONCLUSIONS Chewing gum and coffee did not improve excretion rate in this study. An effect of chewing gum could not be proven, possibly due to sample size. Since chewing gum might improve excretion rates, is cheap and has no known side effects, it needs to be considered in future bowel preparation trials for CCE. TRIAL REGISTRATION NCT02303756 , registered on December 1st 2014.
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Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.
Bashashati, M, Moossavi, S, Cremon, C, Barbaro, MR, Moraveji, S, Talmon, G, Rezaei, N, Hughes, PA, Bian, ZX, Choi, CH, et al
Neurogastroenterology and motility. 2018;(1)
Abstract
BACKGROUND & AIMS Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls. METHODS PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I2 statistics where I2 ≤ 50% and I2 > 50% indicated fixed and random effect models, respectively. KEY RESULTS Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = .02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P = .001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3+ T cells were increased in the rectosigmoid (SMD: 0.53 [95% CI: 0.21-0.85]; P = .001) and the descending colon of the IBS patients (SMD: 0.79, 95% CI [0.28-1.30]; P = .002). This was possibly in relation to higher CD4+ T cells in IBS (SMD: 0.33 [95% CI: 0.01-0.65]; P = .04) as there were no differences in CD8+ T cells. CONCLUSIONS & INFERENCES Mast cells and CD3+ T cells are increased in colonic biopsies of patients with IBS vs non-inflamed controls. These changes are segmental and sometimes IBS-subtype dependent. The diagnostic value of the quantification of colonic mucosal cells in IBS requires further investigation.
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Low colonic absorption drugs: risks and opportunities in the development of oral extended release products.
Xu, J, Lin, Y, Boulas, P, Peterson, ML
Expert opinion on drug delivery. 2018;(2):197-211
Abstract
INTRODUCTION Currently numerous drugs have been observed with lower colonic absorption than small intestine absorption, which can significantly impact in vivo performance of their oral extended release (ER) products. AREAS COVERED We reviewed over 300 publications, patents, book chapters, and commercial reports of drug products from regulatory agencies for low colonic absorption (LCA) drugs and critical findings are discussed. The focuses of this article are (1) current findings on the causes of low colonic absorption to support early assessment of LCA candidates, and (2) current knowledge on successful ER strategies and technical platforms used for LCA drugs in commercial drug products to facilitate oral ER product development. EXPERT OPINION Colonic drug absorption is one of the critical considerations in successful development of oral ER products. The root causes of low colonic absorption in many LCA drugs are still unclear. It is recommended to evaluate colonic drug absorption of drug candidate at early stage of oral ER product development. After evaluation, the selection of a formulation platform to develop an oral ER product needs to be carefully considered for LCA drugs. Based on the current commercial oral ER formulation platforms for LCA drugs, compounds are first divided into five types (I-V) and different ER formulation approaches with higher success rate are recommended for each type.
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Modulation of bacterial metabolism by the microenvironment controls MAIT cell stimulation.
Schmaler, M, Colone, A, Spagnuolo, J, Zimmermann, M, Lepore, M, Kalinichenko, A, Bhatia, S, Cottier, F, Rutishauser, T, Pavelka, N, et al
Mucosal immunology. 2018;(4):1060-1070
Abstract
Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in mucosal tissues and recognize a variety of riboflavin-related metabolites produced by the microbial flora. Relevant issues are whether MAIT cells are heterogeneous in the colon, and whether the local environment influences microbial metabolism thereby shaping MAIT cell phenotypes and responses. We found discrete MAIT cell populations in human colon, characterized by the diverse expression of transcription factors, cytokines and surface markers, indicative of activated and precisely controlled lymphocyte populations. Similar phenotypes were rare among circulating MAIT cells and appeared when circulating MAIT cells were stimulated with the synthetic antigens 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil, and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. Furthermore, bacteria grown in colon-resembling conditions with low oxygen tension and harvested at stationary growth phase, potently activated human MAIT cells. The increased activation correlated with accumulation of the above antigenic metabolites as indicated by mass spectrometry. Thus, the colon environment contributes to mucosal immunity by directly affecting bacterial metabolism, and indirectly controlling the stimulation and differentiation of MAIT cells.
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Eosinophilic colitis: Case series and literature review.
Díaz Del Arco, C, Taxonera, C, Olivares, D, Fernández Aceñero, MJ
Pathology, research and practice. 2018;(1):100-104
Abstract
INTRODUCTION Primary eosinophilic colitis (EC) in adults is a rare and poorly studied disease, with 3 case series, 2 database-based studies and 52 case reports published to date. METHODS Retrospective study of all adult EC cases diagnosed in a large tertiary hospital (Hospital Clínico San Carlos, Madrid) between 2006 and 2016. We included all cases with a histopathological diagnosis of EC and we selected only those cases that were clinically recognized primary EC. We report their clinical, endoscopic and histopathological features and review the literature on this topic. RESULTS We identified 22 primary EC cases. Patients were mostly women (77%) with a mean age of 41 years. 4 patients (18%) had coexistent allergic diseases. Most patients consulted with diarrhea (86%) and 3 patients also suffered from rectal bleeding. Blood tests showed peripheral eosinophilia in 4 cases (18%). 19 patients had no endoscopic lesions, 2 had features of unspecific colitis and one showed features suggestive of IBD. Mean and maximum number of eosinophils per high power field ranged from 16 to 199 and 20 to 253 (mean: 48 and 70). They were mainly located in the lamina propria and most cases were associated with signs of eosinophil activation. Most patients were treated by corticosteroids, diet or budesonide and the result of treatment was generally good. No complications or recurrences were reported. CONCLUSIONS EC etiology and pathogenesis is unknown. Its clinical, endoscopical and imaging features are not specific, and clear histopathological criteria are lacking. Identification of signs of eosinophilic activation could be helpful.
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Goal-directed fluid therapy versus conventional fluid therapy in colorectal surgery: A meta analysis of randomized controlled trials.
Xu, C, Peng, J, Liu, S, Huang, Y, Guo, X, Xiao, H, Qi, D
International journal of surgery (London, England). 2018;:264-273
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Abstract
OBJECTIVES This meta-analysis was conducted to compare the effects of goal-directed fluid therapy (GDFT) versus conventional fluid therapy (CFT) in colorectal surgery on patients' postoperative outcome and to detect whether the results differ between studies with the Enhanced Recovery After Surgery (ERAS) protocol and those without, between studies using different devices for GDFT, or between different surgical approaches (laparoscopy or laparotomy). METHODS The Cochrane Library, PubMed, Embase, Wanfang Data and ClinicalTrials.com were searched for studies from January,1990 to February, 2018. Randomized controlled trials (RCTs) comparing both two abovementioned fluid therapy protocols in colorectal surgery were included. The primary outcome was 30-day mortality after surgery. Secondary outcomes were length of hospital stay (LOS), complication rate, ICU admission and gastrointestinal indicators. RESULTS Eleven studies were included, including a total of 1281 patients: the GDFT group included 624 patients and the control group included 657 patients. No significant differences were found between groups in 30-day mortality (relative risk, RR 0.86,0.28 to 2.63, P = 0.79), LOS (weighted mean difference, WMD 0.22,-0.1 to 0.55, P = 0.18), and ICU admission (RR 0.42, 0.17 to 1.04, P = 0.06). However, the GDFT group had a lower complication rate (RR 0.84,0.71 to 0.99, P = 0.04). In subgroup analyses, time to first flatus and time to tolerate an oral diet were shorter in GDFT group than the control group in studies who did not use the ERAS protocol. No publication bias was identified according to Begg's test. CONCLUSION Compared with conventional fluid therapy, GDFT may not improve patients' postoperative outcome in colorectal surgery. However, the improvement of gastrointestinal function associated with GDFT over conventional fluid therapy was significant in the surgeries that did not use the ERAS protocol.
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Perioperative lipid-enriched enteral nutrition versus standard care in patients undergoing elective colorectal surgery (SANICS II): a multicentre, double-blind, randomised controlled trial.
Peters, EG, Smeets, BJJ, Nors, J, Back, CM, Funder, JA, Sommer, T, Laurberg, S, Løve, US, Leclercq, WKG, Slooter, GD, et al
The lancet. Gastroenterology & hepatology. 2018;(4):242-251
Abstract
BACKGROUND Postoperative ileus and anastomotic leakage severely impair recovery after colorectal resection. We investigated the effect of perioperative lipid-enriched enteral nutrition versus standard care on the risk of postoperative ileus, anastomotic leakage, and other clinical outcomes. METHODS We did an international, multicentre, double-blind, randomised, controlled trial of patients (≥18 years) undergoing elective colorectal surgery with primary anastomosis at six clinical centres in the Netherlands and Denmark. Patients were randomly assigned (1:1), stratified by location (colonic and rectal) and type of surgery (laparoscopic and open), via online randomisation software, with block sizes of six, to receive either continuous lipid-enriched enteral tube feeding from 3 h before until 6 h after surgery (intervention) or no perioperative nutrition (control). Surgeons, patients, and researchers were masked to treatment allocation for the entire study period. The primary outcome was postoperative ileus. Secondary outcomes included anastomotic leakage, pneumonia, preoperative gastric volumes, time to functional recovery, length of hospital stay, the need for additional interventions, intensive care unit admission, postoperative inflammatory response, and surgical complications. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175979, and trialregister.nl, number NTR4670. FINDINGS Between July 28, 2014, and February 20, 2017, 280 patients were randomly assigned, 15 of whom were excluded after random allocation because they fulfilled one or more exclusion criteria. 265 patients received perioperative nutrition (n=132) or standard care (n=133) and were included in the analyses. A postoperative ileus occurred in 37 (28%) patients in the intervention group versus 29 (22%) in the control group (risk ratio [RR] 1·09, 95% CI 0·95-1·25; p=0·24). Anastomotic leakage occurred in 12 (9%) patients in the intervention group versus 11 (8%) in the control group (RR 1·01, 95% CI 0·94-1·09; p=0·81). Pneumonia occurred in ten (8%) patients in the intervention group versus three (2%) in the control group (RR 1·06, 95% CI 1·00-1·12; p=0·051). All other secondary outcomes were similar between groups (all p>0·05). INTERPRETATION Perioperative lipid-enriched enteral nutrition in patients undergoing elective colorectal surgery has no advantage over standard care in terms of postoperative complications. FUNDING Netherlands Organisation for Health Research and Development (ZonMW), Fonds NutsOhra, and Danone Research.
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Isolation of Human Endothelial Cells from Normal Colon and Colorectal Carcinoma - An Improved Protocol.
Naschberger, E, Regensburger, D, Tenkerian, C, Langheinrich, M, Engel, FB, Geppert, C, Hartmann, A, Grützmann, R, Schellerer, VS, Stürzl, M
Journal of visualized experiments : JoVE. 2018;(134)
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Abstract
Primary cells isolated from human carcinomas are valuable tools to identify pathogenic mechanisms contributing to disease development and progression. In particular, endothelial cells (EC) constituting the inner surface of vessels, directly participate in oxygen delivery, nutrient supply, and removal of waste products to and from tumors, and are thereby prominently involved in the constitution of the tumor microenvironment (TME). Tumor endothelial cells (TECs) can be used as cellular biosensors of the intratumoral microenvironment established by communication between tumor and stromal cells. TECs also serve as targets of therapy. Accordingly, in culture these cells allow studies on mechanisms of response or resistance to anti-angiogenic treatment. Recently, it was found that TECs isolated from human colorectal carcinoma (CRC) exhibit memory-like effects based on the specific TME they were derived from. Moreover, these TECs actively contribute to the establishment of a specific TME by the secretion of different factors. For example, TECs in a prognostically favorable Th1-TME secrete the anti-angiogenic tumor-suppressive factor secreted protein, acidic and rich in cysteine-like 1 (SPARCL1). SPARCL1 regulates vessel homeostasis and inhibits tumor cell proliferation and migration. Hence, cultures of pure, viable TECs isolated from human solid tumors are a valuable tool for functional studies on the role of the vascular system in tumorigenesis. Here, a new up-to-date protocol for the isolation of primary EC from the normal colon as well as CRC is described. The technique is based on mechanical and enzymatic tissue digestion, immunolabeling, and fluorescence activated cell sorting (FACS)-sorting of triple-positive cells (CD31, VE-cadherin, CD105). With this protocol, viable TEC or normal endothelial cell (NEC) cultures could be isolated from colon tissues with a success rate of 62.12% when subjected to FACS-sorting (41 pure EC cultures from 66 tissue samples). Accordingly, this protocol provides a robust approach to isolate human EC cultures from normal colon and CRC.
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Diet, Microbiota, and Metabolic Health: Trade-Off Between Saccharolytic and Proteolytic Fermentation.
Korpela, K
Annual review of food science and technology. 2018;:65-84
Abstract
The intestinal microbiota have emerged as a central regulator of host metabolism and immune function, mediating the effects of diet on host health. However, the large diversity and individuality of the gut microbiota have made it difficult to draw conclusions about microbiota responses to dietary interventions. In the light of recent research, certain general patterns are emerging, revealing how the ecology of the gut microbiota profoundly depends on the quality and quantity of dietary carbohydrates and proteins. In this review, I provide an overview of the dependence of microbial ecology in the human colon on diet and how the effects of diet on host health depend partially on the microbiota. Understanding how the individual-specific microbiota respond to short- and long-term dietary changes and how they influence host energy homeostasis will enable targeted interventions to achieve specific outcomes, such as weight loss in obesity or weight gain in malnutrition.