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.

Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases (IBD). Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD. We performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin. METHODS: We performed a single-blind, multicenter study of nonanemic patients who had completed the FERGIcor study. Serum levels of ferritin were assessed every second month, and patients were given FCM (total iron dose, 1181 ± 662 mg; n = 105) or placebo (n = 99) when levels decreased to less than 100 µg/L. The primary end point was time to recurrence of anemia within 8 months. Secondary end points included changes of quality of life, disease activity, results from laboratory tests, and adverse events. RESULTS: Anemia recurred in 26.7% of subjects given FCM and in 39.4% given placebo. The time to anemia recurrence was longer in the FCM group (hazard ratio, 0.62; 95% confidence interval, 0.38-1.00; P = .049). Markers of body levels of iron increased or remained at normal levels in subjects given FCM (ferritin increased by 30.3 µg/L, transferrin saturation increased by 0.6%) but decreased in the group given placebo (ferritin decreased by 36.1 µg/L, transferrin saturation decreased by 4.0%). Changes in quality of life and disease activity were comparable between groups. Adverse events were reported in 59.0% of the FCM group and 50.5% of the placebo group, and serious adverse events were reported in 6.7% and 8.1%, respectively. CONCLUSIONS: FCM prevents recurrence of anemia in patients with IBD, compared with placebo. Nevertheless, the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment.

FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease.

BACKGROUND & AIMS: Iron deficiency anemia (IDA) is common in chronic diseases and intravenous iron is an effective and recommended treatment. However, dose calculations and inconvenient administration may affect compliance and efficacy. We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA. METHODS: This randomized, controlled, open-label, multicenter study included 485 patients with IDA (ferritin <100 µg/L, hemoglobin [Hb] 7-12 g/dL [female] or 7-13 g/dL [male]) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries. Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron, or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron. Primary end point was Hb response (Hb increase ≥ 2 g/dL); secondary end points included anemia resolution and iron status normalization by week 12. RESULTS: The results of 240 FCM-treated and 235 IS-treated patients were analyzed. More patients with FCM than IS achieved Hb response (150 [65.8%] vs 118 [53.6%]; 12.2% difference, P = .004) or Hb normalization (166 [72.8%] vs 136 [61.8%]; 11.0% difference, P = .015). Both treatments improved quality of life scores by week 12. Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience. Deviations from scheduled total iron dosages were more frequent in the IS group. CONCLUSIONS: The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen.

A global perspective on irritable bowel syndrome: a consensus statement of the World Gastroenterology Organisation Summit Task Force on irritable bowel syndrome.

Irritable bowel syndrome (IBS) is common in western Europe and North America, and many aspects of its epidemiology, risk factors, and natural history have been described in these regions. Recent data suggest, however, that IBS is also common in the rest of the world and there has been some evidence to suggest some differences in demographics and presenting features between IBS in the west and as it is experienced elsewhere. The World Gastroenterology Organization, therefore, established a Task Force comprising experts on the topic from all parts of the world to examine IBS from a global perspective. IBS does, indeed, seem to be common worldwide though with some significant variations in prevalence rates between regions and countries and there may well be some potentially interesting variations in presenting symptoms and sex distribution. The global map of IBS is far from complete; community-based prevalence data is not available from many areas. Furthermore, while some general trends are evident in terms of IBS impact and demographics, international comparisons are hampered by differences in diagnostic criteria, study location and methodology; several important unanswered questions have been identified that should form the basis for future collaborative research and have the potential to shed light on this challenging disorder.

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.

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.

Interactions between symptoms and motor and visceral sensory responses of irritable bowel syndrome patients to spasmolytics (antispasmodics).

AIM: to evaluate and correlate the symptomatic, motor and sensory responses to two widely used categories of spasmolytic agents in irritable bowel syndrome (IBS). METHODS: 118 patients with IBS, diagnosed by Rome II criteria and 45 healthy individuals were studied. In the IBS subjects, pain severity, as well as the sensory response to rectal balloon distention and rectal and sigmoid motility, were studied at baseline and after two weeks therapy with either oral buscopan (20 mg three times a day, n=37), a buscopan suppository (30 mg once daily, n=21), oral drotaverine (80 mg three times a day, n=30), calcium gluconate tablets (one three times a day, n=16) as a control for oral agents, or calendula suppository (once daily, n=14) as a control for those who received a suppository. RESULTS: Buscopan, whether administered as a tablet or a suppository, produced a significant reduction in pain scores among IBS patients with predominant diarrhea. No significant differences were evident among other IBS subgroups or in response to drotaverine. None of the interventions had any effect on any of the parameters of rectal or sigmoid motility studied. However, both buscopan and drotaverine led to a significant augmentation of the rectal threshold for discomfort/pain among IBS subjects with predominant diarrhea [21.78 + or - 2.8 vs 39.60 + or - 2.4 (p<0.05), 20.5 + or - 2,8 vs 36.84 + or - 3.8 (p<0.05) and 22.18 + or - 2.8 vs 36.9 + or - 2.42 (p<0.05) for oral buscopan, rectal buscopan and oral drotaverine, respectively]. CONCLUSION: We conclude that the clinical benefits of supposed spasmolytic (anti-spasmodic) agents may relate more to effects on visceral sensation than motility.