PWE-082 The Impact Of Nod2 Variants On Gut Microbiota In Crohn’s Disease And Healthy Controls

Abstract

Methods We studied 8 patients, identified from our anticoagulation database, who had been previously established on warfarin, and then commenced azathioprine or mercaptopurine for inflammatory bowel disease (2), systemic lupus erythematosus (1), nephritic syndrome (1), Wegener's granulomatosis (1), polyarteritis nodosa (1), dermatomyositis (1) and renal transplant (1). The effect of thiopurine on international normalised ratio (INR), and warfarin dose prior to and following commencement of thiopurine was recorded. Results In 6/8 patients, following introduction of azathioprine or mercaptopurine, the warfarin dose had to be significantly increased (100% , Median [range]) in order to maintain a therapeutic INR. Any subsequent reductions in thiopurine dose were mirrored by a rise in INR and lower requirement for warfarin.In 2 IBD patients, each with a high warfarin requirement, thiopurine metabolites were measured. In both patients MeMP: TGN ratio was >11. Thiopurine dose was reduced to 25% and allopurinol 100 mg added. INR was carefully monitored. In both cases INR increased within a week (to 6.9 and 11.2) and warfarin doses were subsequently reduced by ½ and 2/3 respectively to regain therapeutic INR. Conclusion It is important for clinicians to be aware of the potential inhibitory action of thiopurines on warfarin's anticoagulant effect. Close INR monitoring is essential when initiating thiopurines and especially when reducing their dose and/or adding allopurinol. Failure to recognise the latter could result in bleeding due to over-anticoagulation. The high MeMP:TGN ratio in 2 of our patients also raises the possibility that thiopurine metabolites may play a role in the interaction between thiopurines and warfarin. Introduction Faecal calprotectin is recommended by NICE 1 for distinguishing between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in patients with lower gastrointestinal (GI) symptoms in primary care. If cancer is suspected in these patients and 'red-flag' symptoms such as anaemia or bleeding, they should be referred to Gastroenterology in accordance with the NICE suspected cancer guideline. 2 We use calprotectin in secondary care and will be extending the service to primary care providers. However, a number of GPs have been requesting faecal calprotectin on an ad-hoc basis for 1 year, giving us valuable insight into how the test performs in primary care. Methods An audit was carried out of primary care calprotectin data in a 1 year period (Dec 12-Dec 13). This data was compared to an audit of 1 month of secondary care data (Jun 13). Clinical details, such as endoscopy and histology results were extracted from electronic patient records. Results In total 198 requests for calprotectin came from primary care in 1 year and 40 were unsuitable for analysis (wrong sample type or delayed arrival in lab). Of the remaining 158 calprotectin requests, 76% were considered appropriate, having clinical details including symptoms described by NICE. Worryingly, 17% of requests had inappropriat...

Systemic effects of gut microbiota and its relationship with disease and modulation

“…Furthermore, since CD is caused by interactions between genetic and environmental factors, gut microbiota plays a role in the disease. The study confirmed microbiota alterations in CD patients, for example reduction in diversity, decrease in Ruminococcaceae , and increase in Enterbacteriaceae [ 13 ].…”

Recent Advances in Characterizing the Gastrointestinal Microbiome in Crohnʼs Disease

“… 41 , 42 Frank et al 43 demonstrated that the risk alleles at the NOD2 and ATG16L1 loci were associated with significant compositional shifts in their gut microbiota including decreased levels of Faecalibacterium and increased levels of Escherichia. 44 However, conflicting results were found recently by Kennedy et al 44 who found in their study of 40 patients with Crohn's disease of which 58% were found to have an NOD2 variant that the NOD2 allele was not associated with significant taxonomic shifts in gut microbiota. These studies suggest that Crohn's disease-associated loci may well affect the GI microbiome; however, consistent taxonomic shifts have not been demonstrated.…”