Emily K. Wright

Recent advances in characterizing the gastrointestinal microbiome in Crohn's disease: a systematic review.

Background:The intestinal microbiota is involved in the pathogenesis of inflammatory bowel disease. A reduction in the diversity of the intestinal microbiota as well as specific taxonomic and functional shifts have been reported in Crohns disease and may play a central role in the inflammatory process. The aim was to systematically review recent developments in the structural and functional changes observed in the gastrointestinal microbiome in patients with Crohns Disease. Results:Seventy-two abstracts were included in this review. The effects of host genetics, disease phenotype, and inflammatory bowel disease treatment on the gastrointestinal microbiome in Crohns disease were reviewed, and taxonomic shifts in patients with early and established disease were described. The relative abundance of Bacteroidetes is increased and Firmicutes decreased in Crohns disease compared with healthy controls. Enterobacteriaceae, specifically Eschericia coli, is enriched in Crohns disease. Faecalibacterium prausnitzii is found at lower abundance in Crohns disease and in those with postoperative recurrence. Observed functional changes include major shifts in oxidative stress pathways, a decrease in butanoate and propanoate metabolism gene expression, lower levels of butyrate, and other short-chain fatty acids, decreased carbohydrate metabolism, and decreased amino acid biosynthesis. Conclusions:Changes in microbial composition and function have been described, although a causative role remains to be established. Larger, prospective, and longitudinal studies are required with deep interrogation of the microbiome if causality is to be determined, and refined microbial manipulation is to emerge as a focused therapy.

Impact of drug therapy and surgery on quality of life in Crohn's disease: a systematic review.

Abstract:Crohns disease is associated with substantially impaired health-related quality of life (HRQoL). Even in the absence of active disease, patients with Crohns disease report lower HRQoL, poorer function, and greater concerns, than those without disease. Achievement of disease remission in Crohns disease, whether by pharmacological or surgical means, is associated with improved HRQoL, although the durability of the improvement seen after intestinal resection is uncertain because of the high rate of postoperative disease recurrence. This review focuses on the available literature on HRQoL in patients with Crohns disease with an emphasis on the effects of intestinal resection and immunomodulatory therapy.

Fecal biomarkers in the diagnosis and monitoring of Crohn's disease.

Abstract:The diagnosis and monitoring of Crohns disease has traditionally relied on clinical assessment, serum markers of inflammation, and endoscopic examination. Fecal biomarkers such as calprotectin, lactoferrin, and S100A12 are predominantly derived from neutrophils, are easily detectable in the feces, and are emerging as valuable markers of intestinal inflammation. This review focuses on the role of fecal biomarkers in the diagnosis and monitoring of Crohns disease, in particular how these biomarkers change with disease activity and remission, how they can be used to monitor the response to medical therapy, their value in predicting clinical relapse, and their role in monitoring the postoperative state.

Perspectives of paediatric and adult gastroenterologists on transfer and transition care of adolescents with inflammatory bowel disease

Programmes specific to inflammatory bowel disease (IBD) that facilitate transition from paediatric to adult care are currently lacking.

Microbial Factors Associated with Postoperative Crohn’s Disease Recurrence

Background and Aims: The intestinal microbiota is a key antigenic driver in Crohn’s disease [CD]. We aimed to identify changes in the gut microbiome associated with, and predictive of, disease recurrence and remission. Methods: A total of 141 mucosal biopsy samples from 34 CD patients were obtained at surgical resection and at colonoscopy 6 and/or 18 months postoperatively; 28 control samples were obtained: 12 from healthy patients [healthy controls] and 16 from hemicolectomy patients [surgical controls]. Bacterial 16S ribosomal profiling was performed using the Illumina MiSeq platform. Results: CD was associated with reduced alpha diversity when compared with healthy controls but not surgical controls [p < 0.001 and p = 0.666, respectively]. Beta diversity [composition] differed significantly between CD and both healthy [p < 0.001] and surgical [p = 0.022] controls, but did not differ significantly between those with and without endoscopic recurrence. There were significant taxonomic differences between recurrence and remission. Patients experiencing recurrence demonstrated elevated Proteus genera [p = 0.008] and reduced Faecalibacterium [p< 0.001]. Active smoking was associated with elevated levels of Proteus [p = 0.013] postoperatively. Low abundance of Faecalibacterium [< 0.1%] and detectable Proteus in the postoperative ileal mucosa was associated with a higher risk of recurrence (odds ratio [OR] 14 [1.7–110], p = 0.013 and 13 [1.1–150], p = 0.039, respectively) when corrected for smoking. A model of recurrence comprising the presence of Proteus, abundance of Faecalibacterium, and smoking status showed moderate accuracy (area under the curve [AUC] 0.740, 95% confidence interval [CI] [0.69–0.79]). Conclusions: CD is associated with a microbial signature distinct from health. Microbial factors and smoking independently influence postoperative CD recurrence. The genus Proteus may play a role in the development of CD.

Effect of intestinal resection on quality of life in Crohn's disease.

INTRODUCTION Patients with Crohns disease have poorer health-related quality of life [HRQoL] than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug-induced or surgically induced remission, the effects of surgery overall have not been well characterised. METHODS In a randomised trial, patients undergoing intestinal resection of all macroscopically diseased bowel were treated with postoperative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. C-reactive protein [CRP], Crohns Disease Activity Index [CDAI], and faecal calprotectin [FC] were measured preoperatively and at 6, 12, and 18 months. HRQoL was assessed with a general [SF36] and disease-specific [IBDQ] questionnaires at the same time points. RESULTS A total of 174 patients were included. HRQoL was poor preoperatively but improved significantly [p < 0.001] at 6 months postoperatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared with males and non-smokers, respectively. Persistent endoscopic remission, intensification of drug treatment at 6 months, and anti-tumour necrosis factor therapy were not associated with HRQoL outcomes different from those when these factors were not present. There was a significant inverse correlation between CDAI, [but not endoscopic recurrence, CRP, or FC] on HRQoL. CONCLUSION Intestinal resection of all macroscopic Crohns disease in patients treated with postoperative prophylactic drug therapy is associated with significant and sustained improvement in HRQoL irrespective of type of drug treatment or endoscopic recurrence. HRQoL is lower in female patients and smokers. A higher CDAI, but not direct measures of active disease or type of drug therapy, is associated with a lower HRQoL.

Comparison of Fecal Inflammatory Markers in Crohn's Disease.

Background:Fecal biomarkers are used increasingly to monitor Crohns disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection. Methods:Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohns Disease Activity Index (CDAI) were assessed. Results:FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 &mgr;g/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 &mgr;g/g) and were higher in recurrent disease than remission (275 versus 72 &mgr;g/g, P < 0.001; 5.7 versus 1.6 &mgr;g/g, P = 0.007; 2.0 versus 0.8 &mgr;g/g, P = 0.188). FC > 135 &mgr;g/g, FL > 3.4 &mgr;g/g, and FS > 10.5 &mgr;g/g indicated endoscopic recurrence (score ≥ i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not. Conclusions:FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV.

Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application

Evolution of treatment targets in IBD has increased the need for objective monitoring of disease activity to guide therapeutic strategy. Although mucosal healing is the current target of therapy in IBD, endoscopy is invasive, expensive and unappealing to patients. GI ultrasound (GIUS) represents a non-invasive modality to assess disease activity in IBD. It is accurate, cost-effective and reproducible. GIUS can be performed at the point of care without specific patient preparation so as to facilitate clinical decision-making. As compared with ileocolonoscopy and other imaging modalities (CT and MRI), GIUS is accurate in diagnosing IBD, detecting complications of disease including fistulae, strictures and abscesses, monitoring disease activity and detecting postoperative disease recurrence. International groups increasingly recognise GIUS as a valuable tool with paradigm-changing application in the management of IBD; however, uptake outside parts of continental Europe has been slow and GIUS is underused in many countries. The aim of this review is to present a pragmatic guide to the positioning of GIUS in IBD clinical practice, providing evidence for use, algorithms for integration into practice, training pathways and a strategic implementation framework.

Serologic antibodies in relation to outcome in postoperative Crohn's disease

Disease recurs frequently after Crohns disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined.

DOP064 Faecal calprotectin is superior to faecal lactoferrin and S100A12

DOP064 Faecal calprotectin is superior to faecal lactoferrin and S100A12 E.K. Wright1 *, P.P. De Cruz1, M.A. Kamm1, A.L. Hamilton1, K.J. Ritchie1, E.O. Krejany1, S.T. Leach2, J.I. Keenan2, A. Gorelik1, D. Liew1, L. Prideaux1, I.C. Lawrance1, J.M. Andrews1, P.A. Bampton1, M.P. Sparrow1, T.H. Florin1, P.R. Gibson1, H.S. Debinski1, F.A. Macrae1, R.W. Leong1, I.J. Kronborg1, G.L. Radford-Smith1, W.S. Selby1, M.J. Johnson1, R.J. Woods1, P.R. Elliott1, S.J. Bell1, S.J. Brown1, W.R. Connell1, A.S. Day2, R.B. Gearry2, P.V. Desmond1. 1St Vincent’s Hospital & University of Melbourne, Gastroenterology, Melbourne, Australia, 2Christchurch Hospital, Gastroenterology, Christchurch, New Zealand