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.

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.

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.