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.

Archean komatiite volcanism controlled by the evolution of early continents.

The generation and evolution of Earth's continental crust has played a fundamental role in the development of the planet. Its formation modified the composition of the mantle, contributed to the establishment of the atmosphere, and led to the creation of ecological niches important for early life. Here we show that in the Archean, the formation and stabilization of continents also controlled the location, geochemistry, and volcanology of the hottest preserved lavas on Earth: komatiites. These magmas typically represent 50-30% partial melting of the mantle and subsequently record important information on the thermal and chemical evolution of the Archean-Proterozoic Earth. As a result, it is vital to constrain and understand the processes that govern their localization and emplacement. Here, we combined Lu-Hf isotopes and U-Pb geochronology to map the four-dimensional evolution of the Yilgarn Craton, Western Australia, and reveal the progressive development of an Archean microcontinent. Our results show that in the early Earth, relatively small crustal blocks, analogous to modern microplates, progressively amalgamated to form larger continental masses, and eventually the first cratons. This cratonization process drove the hottest and most voluminous komatiite eruptions to the edge of established continental blocks. The dynamic evolution of the early continents thus directly influenced the addition of deep mantle material to the Archean crust, oceans, and atmosphere, while also providing a fundamental control on the distribution of major magmatic ore deposits.

Prevalence of Clostridium Difficile-Associated Diarrhoea in Hospitalised Patients (Results of a Russian Prospective Multicentre Study).

INTRODUCTION: The objective of the study was to evaluate the prevalence of Clostridium difficile-associated diarrhoea (CDAD) among hospitalised patients with antibiotic-associated diarrhoea (AAD) in general and by specific types of medical care and hospital units. METHODS: A prospective, cross-sectional, non-interventional, multicentre study. The main inclusion criteria were: patient age ≥ 18 years, hospital stay of at least 48 h, current antibiotic therapy or antibiotic therapy within the previous 30 days, loose stools (Bristol stool types 5-7 and stool frequency ≥ 3 within ≤ 24 consecutive hours or exceeding normal for the patient) and signed informed consent form. The stool sample was taken to the local (study site) microbiology laboratory for detection of glutamate dehydrogenase (GDH) and toxins A/B using enzyme immunoassay (EIA) stool test. RESULTS: From April 2016 to April 2017, a total of 1245 patients from 12 large hospitals were enrolled in the study. Data on 81 patients were excluded from the analysis for different reasons. Data on 1164 patients (45.2% males and 54.8% females) with a mean age of 54.9 years (range 18-95 years) were analysed. Length of hospitalisation was 2-188 days (median, 8 days). The EIA stool test showed CDAD-positive results in 21.7% (253/1164) patients. The patients were from surgery units (546/1164), internal medicine units (510/1164) and intensive care units (108/1164). The prevalence of CDAD among patients from surgery, internal medicine and intensive care units was 26.2, 17.8 and 17.6%, respectively. Oncology, gastroenterology, septic surgery, oncohaematology and general medical hospital units accounted for more than 75% of all patients included; the prevalence of CDAD by those hospital units was 11.3, 15.0, 39.2, 17.6, and 27.2%, respectively. The proportion of GDH-positive and toxin A/B-negative patients by the rapid stool test result was 16.8% (196/1164). The prevalence of CDAD varied widely between the hospitals (from 0 to 44.3%). CONCLUSIONS: The prevalence of CDAD among hospitalised patients with AAD in this study was 21.7% (95% confidence interval: 14.8 and 28.7%). The percentage of CDAD varied widely between hospitals and by specific types of medical care and hospital units.

3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial.

BACKGROUND AND AIMS: Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3g mesalazine granules OD. METHODS: This was an eight-week randomised, double-blind, double-dummy, multicentre study in which patients with mild-to-moderately active UC, defined as Clinical Activity Index (CAI) ≥6 and Endoscopic Index (EI) ≥4, received budesonide (Budenofalk® 3mg capsules×3) or mesalazine (Salofalk® 1000mg granules×3). The primary endpoint was clinical remission at week 8 (CAI ≤4 with stool frequency and rectal bleeding subscores of "0"). RESULTS: 343 patients were randomised (177 budesonide, 166 mesalazine). Fewer patients achieved the primary endpoint with budesonide versus mesalazine (70/177 [39.5%] versus 91/166 [54.8%]) with a difference in proportions of -15.3% (95% CI [-25.7%, -4.8%]; p=0.520 for non-inferiority). The median time to first resolution of symptoms was 14.0 days (budesonide) and 11.0 days (mesalazine) (hazard ratio 1.19; 95% CI [0.94, 1.51]). Mucosal healing was observed in 54/177 (30.5%) budesonide patients versus 65/166 (39.2%) mesalazine patients, a difference of -8.6% (95% CI [-18.7%, 1.4%]; p=0.093). The incidences of adverse events (budesonide 26.6%, mesalazine 25.3%) and serious adverse events (budesonide 1.7%, mesalazine 1.2%) were similar. CONCLUSIONS: Once-daily 3g mesalazine administered as granules is superior to 9mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC. However, it is noteworthy that remission of UC was attained in about 40% of budesonide-treated patients with a rapid onset of resolution.