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Clinical and Translational Gastroenterology

Julia König, Jerry Wells, Patrice D Cani, Clara L García-Ródenas, Tom MacDonald, Annick Mercenier, Jacqueline Whyte, Freddy Troost, Robert-Jan Brummer
The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed...
October 20, 2016: Clinical and Translational Gastroenterology
Darwin L Conwell, David C Whitcomb
The pancreas remains a challenging organ to assess because of its retroperitoneal locations and cost of accessing the pancreatic duct for collection of biological samples. A novel and potentially useful approach to analysis of pancreatic juice proteins has been developed by Rocker et al. (Clin Transl Gastroenterol 7: e174; doi:10.1038/ctg.2016.27) using whole-gut lavage fluid from a colonoscopy prep. The widespread use of colonoscopy for colon cancer screening provides the opportunity to also screen the patient for benign and malignant pancreatic diseases using the fluid waste...
October 13, 2016: Clinical and Translational Gastroenterology
Cedric Peleman, Michael Camilleri
Rifaximin is beneficial in the treatment of minimal hepatic encephalopathy (MHE). Kang et al. (Clin Transl Gastroenterol 7: e187; doi:10.1038/ctg.2016.44) investigated the effects of rifaximin in a mouse model of MHE-associated microbiota without concomitant liver disease. In addition to some impact on the composition of microbiota, rifaximin altered bacterial functions, ameliorated local and systemic inflammation, and reduced enterocyte glutaminase activity. We discuss these effects as well as the interpretation of the permeability studies, given the potential interaction of dysbiosis with dysfunctional intestinal barrier, leading to systemic inflammation and increased uptake of bacterial metabolites that contribute to MHE in the presence of hepatic dysfunction...
October 6, 2016: Clinical and Translational Gastroenterology
Monica A Konerman, Anna S F Lok
Current treatment for chronic hepatitis C (CHC) is highly efficacious, well-tolerated, and of short duration for the majority of patients. Despite the dramatic advances in therapy, there remain several barriers to disease eradication. These include deficiencies in screening, diagnosis, and access to care, and high cost of the direct-acting antiviral medications. In addition, incident cases and reinfection associated with injection drug use contribute to the persistent worldwide disease burden. This article will review the current CHC treatments, and outline the remaining gaps in therapy and barriers to disease eradication...
2016: Clinical and Translational Gastroenterology
Christopher R Heier, Alyson A Fiorillo, Ellen Chaisson, Heather Gordish-Dressman, Yetrib Hathout, Jesse M Damsker, Eric P Hoffman, Laurie S Conklin
OBJECTIVE: Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial. METHODS: We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7)...
2016: Clinical and Translational Gastroenterology
Carina Pereira, Sara Queirós, Ana Galaghar, Hugo Sousa, Ricardo Marcos-Pinto, Pedro Pimentel-Nunes, Catarina Brandão, Rui Medeiros, Mário Dinis-Ribeiro
OBJECTIVES: Deregulation of prostaglandin E2 (PGE2) levels reported in colorectal carcinogenesis contributes to key steps of cancer development. Our aim was to evaluate the influence of the genetic variability in COX-2/HPGD/SLCO2A1/ABCC4 PGE2 pathway genes on the development and recurrence of colorectal adenomas. METHODS: A case-control study was conducted gathering 480 unscreened individuals and 195 patients with personal history of adenomas. A total of 43 tagSNPs were characterized using the Sequenom platform or real-time PCR...
2016: Clinical and Translational Gastroenterology
Ruma Rajbhandari, Raymond T Chung
No abstract text is available yet for this article.
2016: Clinical and Translational Gastroenterology
Benjamin Click, David C Whitcomb
Managing the health of individual patients suffering from complex disorders is a challenge and is costly. Inflammatory bowel disease (IBD) is a prototypic complex disorder of the small and large intestines. Susceptibility is complex, severity is variable, and response to treatment is unpredictable. Di Narzo et al. (Clin Transl Gastroenterol 7: e177; doi:10.1038/ctg.2016.34) bring diverse teams of physicians and scientists together to break down the mechanisms of IBD by linking pathogenic genetic variants with altered gene expression in specific cell types causing IBD...
2016: Clinical and Translational Gastroenterology
Brooke R Druliner, Xiaoyang Ruan, Ruth Johnson, Diane Grill, Daniel O'Brien, Tsung-Po Lai, Shahrooz Rashtak, Donna Felmlee-Devine, Jill Washechek-Aletto, Andrei Malykh, Thomas Smyrk, Ann Oberg, Hongfang Liu, Jerry W Shay, David A Ahlquist, Lisa A Boardman
OBJECTIVE: Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free. METHODS: Tissues were identified as cancer-adjacent polyp (CAP)-residual adenoma contiguous with cancer-and cancer-free polyp (CFP)-adenomas without malignancy...
2016: Clinical and Translational Gastroenterology
Dae J Kang, Genta Kakiyama, Naga S Betrapally, Jeremy Herzog, Hiroshi Nittono, Phillip B Hylemon, Huiping Zhou, Ian Carroll, Jing Yang, Patrick M Gillevet, Chunhua Jiao, Hajime Takei, William M Pandak, Takashi Iida, Douglas M Heuman, Sili Fan, Oliver Fiehn, Takao Kurosawa, Masoumeh Sikaroodi, R B Sartor, Jasmohan S Bajaj
OBJECTIVES: Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin. METHODS: Four germ-free (GF) mice groups were used (1) GF, (2) GF+rifaximin, (3) Humanized with stools from an MHE patient, and (4) Humanized+rifaximin...
2016: Clinical and Translational Gastroenterology
Jacqueline M Lankelma, Clara Belzer, Arie J Hoogendijk, Alex F de Vos, Willem M de Vos, Tom van der Poll, W Joost Wiersinga
OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however, evidence in humans is lacking. METHODS: Twelve healthy young men were given oral broad-spectrum antibiotics (ciprofloxacin 500 mg bid, vancomycin 500 mg tid and metronidazole 500 mg tid) for 7 days...
2016: Clinical and Translational Gastroenterology
Renee Williams, Pascale White, Jose Nieto, Dorice Vieira, Fritz Francois, Frank Hamilton
This review is an update to the American College of Gastroenterology (ACG) Committee on Minority Affairs and Cultural Diversity's paper on colorectal cancer (CRC) in African Americans published in 2005. Over the past 10 years, the incidence and mortality rates of CRC in the United States has steadily declined. However, reductions have been strikingly much slower among African Americans who continue to have the highest rate of mortality and lowest survival when compared with all other racial groups. The reasons for the health disparities are multifactorial and encompass physician and patient barriers...
2016: Clinical and Translational Gastroenterology
Hiroyuki Yamamoto, Yoshiyuki Watanabe, Ritsuko Oikawa, Ryo Morita, Yoshihito Yoshida, Tadateru Maehata, Hiroshi Yasuda, Fumio Itoh
OBJECTIVES: The main purpose of this study was to develop a methylation analysis pipeline by using gastric wash-derived DNA and/or gastric juice-derived exosomal DNA (exoDNA), and to evaluate its suitability for the early detection of gastric cancer (GC) in clinical settings. METHODS: We analyzed alterations of BarH-like 2 homeobox protein (BARHL2) in GC cell lines and tissues, as well as in DNA obtained from 128 gastric washes and 30 gastric juice-derived exosomes...
2016: Clinical and Translational Gastroenterology
Valli De Re, Enrico Orzes, Vincenzo Canzonieri, Stefania Maiero, Mara Fornasarig, Lara Alessandrini, Silvia Cervo, Agostino Steffan, Giorgio Zanette, Cinzia Mazzon, Paolo De Paoli, Renato Cannizzaro
OBJECTIVES: The objectives of this study were to investigate the serum pepsinogen test for the prediction of OLGIM (Operative Link on Gastric Intestinal Metaplasia Assessment) stages in first-degree relatives (FDR-GC) of patients with gastric cancer (GC) and autoimmune chronic atrophic gastritis (ACAG). METHODS: In 67 consecutive patients with ACAG, 82 FDR-GC, and 53 controls (CTRL) without gastric disease (confirmed by biopsy), serum levels of pepsinogen 1 (PG1), pepsinogen 2 (PG2), G17, and the PG1/2 ratio were assessed by enzyme-linked immunosorbent assay kit...
2016: Clinical and Translational Gastroenterology
Moira Paroni, Andrea Magarotto, Silvia Tartari, Giulia Nizzoli, Paola Larghi, Giulia Ercoli, Umberto Gianelli, Massimiliano Pagani, Luca Elli, Sergio Abrignani, Dario Conte, Jens Geginat, Flavio Caprioli
OBJECTIVES: To provide a functional and phenotypic characterization of immune cells infiltrating small intestinal mucosa during non-IPEX autoimmune enteropathy (AIE), as to gain insights on the pathogenesis of this clinical condition. METHODS: Duodenal biopsies from a patient with AIE at baseline and following drug-induced remission were analyzed by immunohistochemistry, immunofluorescence, and flow cytometry, and results were compared with those obtained from patients with active celiac disease, ileal Crohn's disease and healthy controls...
2016: Clinical and Translational Gastroenterology
Jianfei Jiang, Benjamin Click, Alyce M Anderson, Ioannis E Koutroubakis, Claudia Ramos Rivers, Jana G Hashash, Michael A Dunn, Marc Schwartz, Jason Swoger, Arthur Barrie, Miguel Regueiro, Chung-Chou H Chang, David G Binion
OBJECTIVES: Inflammatory bowel disease (IBD) is a heterogeneous group of chronic inflammatory gastrointestinal conditions with variable disease courses often requiring significant healthcare expenditures. We aimed to identify disease trajectory patterns based on longitudinal financial expenditures and to assess the association of classic disease activity parameters with financial charges. METHODS: This was an analysis of a consented, prospective, natural history IBD registry (2009-2013) from a tertiary IBD center of 2,203 patients and their associated medical charges excluding pharmacy expenses...
2016: Clinical and Translational Gastroenterology
Ricardo U Macías-Rodríguez, Hermes Ilarraza-Lomelí, Astrid Ruiz-Margáin, Sergio Ponce-de-León-Rosales, Florencia Vargas-Vorácková, Octavio García-Flores, Aldo Torre, Andrés Duarte-Rojo
OBJECTIVES: Exercise has been scarcely studied in patients with cirrhosis, and prior evidence showed hepatic venous pressure gradient (HVPG) to be increased in response to exercise. The aim of this study was to investigate the effects of a supervised physical exercise program (PEP) in patients with cirrhosis. METHODS: In an open-label, pilot clinical trial, patients with cirrhosis were randomized to PEP (cycloergometry/kinesiotherapy plus nutritional therapy, n=14) or control (nutritional therapy, n=15); for 14 weeks...
2016: Clinical and Translational Gastroenterology
Yumiko Nagao, Kanae Kimura, Yuji Kawahigashi, Michio Sata
OBJECTIVES: Oral lichen planus (OLP) is one of the extrahepatic manifestations of hepatitis C virus (HCV) infection. Presently developed interferon (IFN)-free direct-acting antivirals (DAAs) used to treat HCV infection have low side effect profiles and high efficacy. However, there are no studies examining the relationship between OLP and IFN-free DAAs. The aim of this study was to evaluate the disease course in patients with HCV-associated OLP, who received treatment with IFN-free DAAs...
2016: Clinical and Translational Gastroenterology
Diana Di Liberto, Pasquale Mansueto, Alberto D'Alcamo, Marianna Lo Pizzo, Elena Lo Presti, Girolamo Geraci, Francesca Fayer, Giuliana Guggino, Giuseppe Iacono, Francesco Dieli, Antonio Carroccio
OBJECTIVES: Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS. METHODS: The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge...
2016: Clinical and Translational Gastroenterology
Antonio F Di Narzo, Lauren A Peters, Carmen Argmann, Aleksandar Stojmirovic, Jacqueline Perrigoue, Katherine Li, Shannon Telesco, Brian Kidd, Jennifer Walker, Joel Dudley, Judy Cho, Eric E Schadt, Andrew Kasarskis, Mark Curran, Radu Dobrin, Ke Hao
OBJECTIVES: Genome-wide association studies (GWAS) have identified loci reproducibly associated with inflammatory bowel disease (IBD) and other immune-mediated diseases; however, the molecular mechanisms underlying most of genetic susceptibility remain undefined. Expressional quantitative trait loci (eQTL) of disease-relevant tissue can be employed in order to elucidate the genes and pathways affected by disease-specific genetic variance. METHODS: In this study, we derived eQTLs for human whole blood and intestine tissues of anti-tumor necrosis factor-resistant Crohn's disease (CD) patients...
2016: Clinical and Translational Gastroenterology
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