Incidence of suboptimal response to tumor necrosis factor antagonist therapy in inflammatory bowel disease in newly industrialised countries: The EXPLORE study.

BACKGROUND: Incidence of inflammatory bowel disease (IBD) is increasing in newly industrialised countries (NICs); however, data on suboptimal response to anti-tumor necrosis factor (anti-TNF) agents are limited. OBJECTIVES: To assess incidence and indicators of suboptimal response to first anti-TNF therapy in IBD patients in NICs. METHODS: A chart review was conducted in ten countries from Asia-Pacific (APAC), Latin America (LatAm), and Russia and the Middle East (RME) regions among patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD), initiating anti-TNF therapy in 2010-2015. The cumulative incidence of suboptimal response to anti-TNF therapy was assessed using the following indicators: dose escalation or discontinuation, augmentation with non-biologic therapy, IBD-related hospitalization, or surgery. RESULTS: The study included 1,674 patients (570 UC; 1,104 CD). At 24 months, 32.9% of UC (APAC: 45.1%; LatAm: 38.2%; RME: 23.8%) and 41.2% of CD patients (APAC: 54.1%; LatAm: 42.5%; RME: 29.5%) had experienced suboptimal response. The most frequent first indicator was non-biologic therapy augmentation in LatAm (41.7%), IBD-related hospitalization in RME (UC: 50.7%; CD:37.3%) and in APAC for CD (39.1%), and anti-TNF discontinuation in APAC for UC (38.3%). CONCLUSION: Suboptimal response to anti-TNF agents is common in IBD patients in NICs. Observed regional differences in the incidence and indicators may reflect local practice and anti-TNF restrictions in IBD management. NCT REGISTRATION NUMBER: NCT03090139.

Proteomic dataset: Profiling of cultivated Echerichia coli isolates from Crohn's disease patients and healthy individuals.

One of the dysbioses often observed in Crohn's disease (CD) patients is an increased abundance of Escherichia coli (10-100 fold compared to healthy individuals) (Gevers et al., 2014). The data reported is a large-scale proteome profile for E. coli isolates collected from CD patients and healthy individuals. 43 isolates were achieved from 30 CD patients (17 male, 12 female, median age 30) and 19 isolates from 7 healthy individuals (7 male, median age 19). Isolates were cultivated on LB medium at aerobic conditions up to medium log phase. Protein extraction was performed with sodium deoxycholate (DCNa) and urea, alcylation with tris(2-carboxyethyl)phosphine and iodacetamide. Protein trypsinolysis was performed as described in (Matyushkina et al., 2016). Total cell proteomes were analysed by shotgun proteomics with HPLC-MS/MS on a maXis qTOF mass-spectrometer. The data including HPLC-MS/MS raw files and exported Mascot search results was deposited to the PRIDE repository project accession: PXD010920, project https://doi.org/10.6019/PXD010920.

Multiple Cytokine Profiling: A New Model to Predict Response to Tumor Necrosis Factor Antagonists in Ulcerative Colitis Patients.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is a form of inflammatory bowel disease, and antibodies against tumor necrosis factor (anti-TNF) are used for treatment. Many patients are refractory or lose response to anti-TNF, and predicting response would be an extremely valuable clinical tool. Unlike most biomarkers, cytokines directly mediate inflammation, and their measurement may predict the likelihood of response or no response. METHODS: Serum samples were obtained from 49 UC patients before infliximab infusions, and levels of 17 cytokines were measured using a multiplex assay. The Fisher linear discriminant analysis (FLDA) was applied to the cytokine values to predict which patients would respond to infliximab. "Response" was defined as clinical remission after the third infusion, and "no response" was defined as lack of remission after the third infusion. RESULTS: The Fisher linear discriminant analysis model identified a subset of seven predictor cytokines: TNF-α, IL-12, IL-8, IL-2, IL-5, IL1-ß, and IFN-γ. The obtained canonical coefficients enabled to calculate discriminant scores as linear combinations of the cytokines; model classified thepatients as responders and nonresponders with a sensitivity of 84.2% and a specificity of 93.3%. Overall, the yield of the FLDA model was 89.8% of the total 49 patients. CONCLUSIONS: An unbiased, statistically derived, predictive model based on measurement of serum cytokines before therapy may predict a positive or negative outcome from the administration of anti-TNF to UC patients. Because accurately measuring cytokines is simple and inexpensive, the model may be a valuable new tool to complement other laboratory parameters used in the management of IBD patients.

Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn's disease discovered using metagenomic and genomic analyses.

BACKGROUND: Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated. METHODS: We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability. RESULTS: The abnormal shifts in the microbial community structures in Crohn's disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes. CONCLUSIONS: The genomic diversity of Crohn's disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn's disease and the development of new strategies for the prevention and treatment of this disease.

Genome analysis of E. coli isolated from Crohn's disease patients.

BACKGROUND: Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related. RESULTS: We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons. CONCLUSIONS: Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.

Inflammatory bowel disease treatment in Eastern Europe: current status, challenges and needs.

PURPOSE OF REVIEW: To analyze the available studies of course, diagnosis and treatment of Inflammatory bowel disease (IBD) in Eastern Europe. RECENT FINDINGS: According to published data, full epidemiological studies were conducted only in Czech Republic, Estonia, Hungary and Romania. Russia was recently included in the EpiCom study, although only Moscow region data were provided. SUMMARY: We summarize previously published and unpublished data on the epidemiology, IBD diagnosis and treatment in Eastern Europe. In addition, changes during several years are presented. These data show that IBD epidemiology in Eastern Europe corresponds to the previously known patterns, and that the quality of IBD health care has improved in the last several years.