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Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years?

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World Journal of Gastroenterology 2014年第5期20卷 1192-1210页

作者： Georgina L Hold Megan Smith Charlie Grange Euan Robert Watt Emad M El-Omar Indrani Mukhopadhya Gastro-intestinal Research Group Division of Applied Medicine University of Aberdeen Foresterhill

Our understanding of the microbial involvement in inflammatory bowel disease(IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn's disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity(including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.

关键词： Inflammatory bowel disease Crohn’s dis-ease ulcera

Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis

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World Journal of Gastroenterology 2014年第17期20卷 4980-4986页

作者： Burton I Korelitz Keith Sultan Megha Kothari Leo Arapos Judy Schneider Georgia Panagopoulos Department of Gastroenterology Lenox Hill HospitalNew YorkNY 10075United States Department of Gastroenterology and Hepatology and Nutrition North Shore HospitalManhassetNY 11030United States North Oaks Medical Center HammondLA 70403United States Department of Research Lenox Hill HospitalNew YorkNY 10075United States

AIM:To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer(CC)or high grade dysplasia(HGD).METHODS:This is a single center(Lenox Hill Hospital)retrospective cohort and descriptive study of extensive ulcerative colitis(UC)for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis.Data analyzed included:duration of UC,date of diagnosis of(CC)or(HGD),number of surveillance colonoscopies,and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal.Two subgroups of patients were compared:group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD.RESULTS:Of 115 patients with longstanding UC reviewed,68 patients met the inclusion criteria.Twenty patients were in group 1 and 48 in group 2.We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation.Overall,histological disease activity in the absence of gross/endoscopic disease was found in 31.2%(95%CI:28%-35%)of colonoscopies performed on the entire cohort of 68 patients.Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients,88%(95%CI:72%-97%)vs 59%(95%CI:53%-64%).Only 3/20(15%)of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity(i.e.,no endoscopic or histological activity)as compared to 37/48(77%)of patients in group 2,and only 3.3%(95%CI:0.09%-8.3%)of colonoscopies in group 1 had no histological inflammation compared to23%(95%CI:20%-27%)in group 2.CONCLUSION:Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrate persistent histological inflammation in the absence of gross mucosal disease.

关键词： Histological inflammation Risk Colon cancer ulcera

Inflammatory bowel disease in an underdeveloped region of Northeastern Brazil

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World Journal of Gastroenterology 2015年第4期21卷 1197-1206页

作者： José Miguel Luz Parente Claudio Saddy Rodrigues Coy Viriato Campelo Mírian Perpétua Palha Dias Parente Leonardo Araújo Costa Renata Mendes da Silva Celso Stephan José Murilo Robilotta Zeitune Center for Health Sciences Federal University of Piaui (Universidade Federal do Piauí - UFPI)TeresinaPiauí 64049-550Brazil Department of Surgery School of Medical SciencesState University of Campinas (Universidade Estadual de Campinas)CampinasS?o Paulo 13083-970Brazil Center of Health Sciences State University of Piaui (Universidade Estadual do Piauí - UESPI)TeresinaPiauí 64001-280Brazil Federal University of Piaui (Universidade Federal do Piauí - UFPI) TeresinaPiauí 64049-550Brazil Department of Public Health School of Medical SciencesState University of Campinas (Universidade Estadual de Campinas - Unicamp)CampinasS?o Paulo 13083-970Brazil Department of Internal Medicine School of Medical SciencesState University of Campinas (Universidade Estadual de Campinas - Unicamp)CampinasS?o Paulo 13083-970Brazil

AIM: To evaluate the demographic characteristics and clinical phenotypes of inflammatory bowel disease(IBD) in a geographic area in Northeastern Brazil.METHODS: This retrospective study was conducted at the Hospital of the Federal University of Piauí in Northeastern Brazil. Demographic characteristics and clinical phenotypes of IBD were analyzed in relation to the time of diagnostic confirmation, which was defined as the date of disease onset. Data were collected between January 2011 and December 2012 and included all census patients 18 years of age or older during that period for whom there was diagnostic confirmation of Crohn's disease(CD), ulcerative colitis(UC), or unclassified colitis according to the Montreal criteria. We also analyzed the period of time between the onset of clinical manifestations and the diagnosis of IBD(delay in the diagnosis). Statistical analyses included means and standard deviations for numeric variables and the Pearson χ2 adherence test for nominal variables. The annual index occurrence and overall prevalence of IBD at our institution were also calculated, with P values < 0.05 indicating statistical significance. This study was approved by the Institutional Ethics and Research Committee.RESULTS: A total of 252 patients with IBD were included, including 152(60.3%) UC patients and 100(39.7%) CD patients. The clinical and demographic characteristics of all patients with IBD showed a female to male ratio of 1.3:1.0 and a mean age of35.2(SD = 14.5) years. In addition, the majority of patients were miscegenated(171, 67.9%), had received higher education(157, 62.4%), lived in urban areas(217, 86.1%), and were under the age of 40 years(97, 62.5%). For patients with CD, according to the Montreal classification, the predominant features present from the onset of disease were an age between 17 and 40 years(A2); colonic disease location(L2); and nonstricturing, nonfistulizing disease behavior(B1). However, approximately one-quarter of all CD patients demonstrated perineal involvement. We also o

关键词： Inflammatory bowel diseases Crohn’s disease ulcera

Inflammatory bowel disease and thromboembolism

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World Journal of Gastroenterology 2014年第38期20卷 13863-13878页

作者： Petros Zezos Georgios Kouklakis Fred Saibil Gastrointestinal Endoscopy Unit University General Hospital of AlexandroupolisDemocritus University of Thrace Division of Gastroenterology Department of Medicine Sunnybrook Health Sciences CentreUniversity of Toronto

Patients with inflammatory bowel disease(IBD) have an increased risk of vascular complications. Thromboembolic complications,both venous and arterial,are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to Thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown,but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature,as well as in the systemic circulation. Clinicians' awareness of the risks,and their ability to promptly diagnose and manage TEs are of vital importance. In this review we discuss how thromboembolic disease is related to IBD,specifically focusing on:(1) the epidemiology and clinical features of thromboembolic complications in IBD;(2) the pathophysiology of thrombosis in IBD;and(3) strategies for the prevention and management of thromboembolic complications in IBD patients.

关键词： Inflammatory bowel disease Crohn’s dis-ease ulcera

Neurological disorders and inflammatory bowel diseases

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World Journal of Gastroenterology 2014年第27期20卷 8764-8782页

作者： Giovanni Casella Gian Eugenio Tontini Gabrio Bassotti Luca Pastorelli Vincenzo Villanacci Luisa Spina Vittorio Baldini Maurizio Vecchi Medical Department Desio Hospital Gastroenterology and Gastrointestinal Endoscopy Unit IRCCS Policlinico San Donato 20097 San Donato Milanese Italy Gastroenterology Section Department of Medicine University of Perugia Medical School Department of Biomedical Sciences for the Health University of Milan Institute of Pathology Spedali Civili 25123 Brescia Italy

Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease(IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.

关键词： Inflammatory bowel diseases Crohn’s disease ulcera

Temporal trends in inflammatory bowel disease publications over a 19-years period

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World Journal of Gastroenterology 2014年第44期20卷 16745-16749页

作者： Yael Weintraub Francis B Mimouni Shlomi Cohen Pediatric Gastroenterology and Nutrition Unit "Dana-Dwek" Children’s Hospital Tel Aviv Medical Center Sackler Faculty of Medicine Tel Aviv University Department of Pediatrics "Dana-Dwek" Children’s Hospital Tel Aviv Medical Center and Sackler Faculty of Medicine Tel Aviv University Division of Neonatology Shaare Zedek Medical Center

AIM: To determine whether temporal changes occurred in the pediatric vs adult inflammatory bowel disease(IBD), both in terms of number and type of yearly published articles.METHODS:We aimed to evaluate all Pub Med-registered articles related to the field of IBD from January1,1993 and until December 31,2011.We searched for articles using the key words"inflammatory bowel disease"or"Crohn’s disease"or"ulcerative colitis"or"undetermined colitis",using the age filters of"child"or"adult".We repeated the search according to the total number per year of articles per type of article,for each year of the specified period.We studied randomized controlled trials,clinical trials,case reports,meta-analyses,letters to the editor,reviews,systematic reviews,practice guidelines,and editorials.RESULTS:We identified 44645 articles over the 19year-period.There were 8687 pediatric-tagged articles vs 19750 adult-tagged articles.Thus 16208 articles were unaccounted and not assigned a"pediatric"or"adult"tag by Pub Med.There was an approximately3-fold significant increase in all articles recorded both in pediatric and adult articles.This significant increase was true for nearly every category of article but the number of clinical trials,meta-analysis,and randomized controlled trials increased proportionally more than the number of"lower quality"articles such as editorials or letters to the editor.Very few guidelines were published every year.CONCLUSION:There is a yearly linear increase in publications related to IBD.Relatively,there are more and more clinical trials and higher quality articles.

关键词： Inflammatory bowel disease Crohn’s dis-ease ulcera

Pulmonary manifestations of inflammatory bowel disease

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World Journal of Gastroenterology 2014年第37期20卷 13501-13511页

作者： Xiao-Qing Ji Li-Xia Wang De-Gan Lu Department of Respiratory Medicine Shandong Provincial Qianfoshan Hospital Division of Disinfectant and Supply Liaocheng People’s Hospital

Extraintestinal manifestations of inflammatory bowel disease(IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered inthe case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.

关键词： Inflammatory bowel diseases Crohn’s disease ulcera