Tag Archives: Microbiota research

C. diff. Research and Development Community October 2015

laboratorybeakers3

Here is the latest from the Clostridium difficile research community

 

 

 

Serum 25-hydroxyvitamin D levels are not associated with adverse outcomes in                        Clostridium difficile infection

Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI.

For full article click on the link below:

http://www.pagepress.org/journals/index.php/idr/article/view/5979

 

Clostridium difficile is a Gram-positive spore-forming pathogen and a leading cause of nosocomial diarrhea. C. difficile infections are transmitted when ingested spores germinate in the gastrointestinal tract and transform into vegetative cells. Germination begins when the germinant receptor CspC detects bile salts in the gut. CspC is a subtilisin-like serine pseudoprotease that activates the related CspB serine protease through an unknown mechanism. Activated CspB cleaves the pro-SleC zymogen, which allows the activated SleC cortex hydrolase to degrade the protective cortex layer. While these regulators are essential for C. difficile spores to outgrow and form toxin-secreting vegetative cells, the mechanisms controlling their function have only been partially characterized. In this study, we identify the lipoprotein GerS as a novel regulator of C. difficile spore germination using targeted mutagenesis. A gerS mutant has a severe germination defect and fails to degrade cortex even though it processes SleC at wildtype levels. Using complementation analyses, we demonstrate that GerS secretion, but not lipidation, is necessary for GerS to activate SleC. Importantly, loss of GerS attenuates the virulence of C. difficile in a hamster model of infection. Since GerS appears to be conserved exclusively in related Peptostreptococcaeace family members, our results contribute to a growing body of work indicating that C. difficile has evolved distinct mechanisms for controlling the exit from dormancy relative to B. subtilis and other spore-forming organisms.

For full article click on the link below:

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005239

 

XBiotech  the world’s leading developer of next-generation True Human™ therapeutic antibodies, announced today the launch of a research and development program to develop a first-in-class oral monoclonal antibody against Clostridium difficile (C. difficile) infection. Using its proprietary True Human technology, the Company has begun screening human blood samples from donors to identify and clone a therapeutic antibody candidate from individuals with natural immunity to C. difficile infection.

For full article click on the link below:

In a 1-year survey at a university hospital we found that 20·6% (81/392) of patients with antibiotic associated diarrohea where positive for C. difficile. The most common PCR ribotypes were 012 (14·8%), 027 (12·3%), 046 (12·3%) and 014/020 (9·9). The incidence rate was 2·6 cases of C. difficile infection for every 1000 outpatients.
For full article click on the link below:

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=10011117&fileId=S0950268815002459

Microbiota Changes Predict Treatment Failure
Infection with C. difficile is associated with several adverse outcomes including treatment failure (5% to 35%) but researchers do not know what clinical factors can predict this failure.

Reporting at the American College of Gastroenterology Scientific Meeting in Honolulu, a Mayo Clinic team of researchers looked at which gut microbiota signatures might be useful in determining whether patients will get better.

They defined treatment failure as a non-response to treatment with vancomycin for four days or metronidazole for five days. They looked at 889 patients with primary C. dif in infection (CDI) of whom 60.2% were women and the median age was 54 years. Of these 7% had severe CDI, 70.5% had been treated with metronidazole, 23.8% with vancomycin, and 5.6% with a combination.

Overall 12.5% failed treatment and the rates were similar with each drug.

The researchers looked at clinical factors that might have predicted the failures–age, sex, obesity, prior antibiotic use, and other factors. They found no correlation between having those factors and failing treatment. They did find that patients who responded to treatment had higher quantities of certain bacteria, for instance Faecalibacterium and Bacteroides.

Conversely, the patients who failed treatment had more Streptococcus and Clostridium.

The authors suggest that analyzing these changes in microbiota could be useful. “Gut microbiota signatures may be used to predict treatment response in the absence of reliable clinical predictors,” said Sahil Khanna, MBBS, M S in presenting the study.

For full article click on the link below:

Study Shows the importance of Gut Microbiota in Stem Cell Transplant Outcome

In The News 17 June 2014

New  research published online today in Blood, the Journal of the American Society of Hematology (ASH), suggests that the diversity of bacteria in the gastrointestinal tract of patients receiving stem cell transplants may be an important predictor of their post-transplant survival.

A healthy gastrointestinal tract contains a balanced community of microorganisms (known as microbiota), largely comprised of “friendly” bacteria that aid digestion and are important to immune system function. When this community of microbes is compromised, the microbiota may become less diverse, and the body becomes more susceptible to certain diseases.

Previous studies have shown that the intensive treatment given to individuals receiving a stem cell transplant from a healthy donor (known as an allogeneic stem cell transplant or SCT) can destroy a significant portion of the recipients’ gut microbiota and reduce its overall diversity. Disturbances of the gut microbiota have been shown to be correlated with post-transplant complications such as bloodstream infections and graft-versus-host disease.

“While the link between gut microbiota and complications in allogeneic SCT has been previously established, until this point it has remained unclear whether the gut bacteria of transplant recipients could predict their survival,” said senior study author Ying Taur, MD, MPH, of the Lucille Castori Center for Microbes, Inflammation, and Cancer at Memorial Sloan Kettering Cancer Center. “This study sought to further explore the potential connection between transplantation, gut bacteria, and overall survival.”

To better understand the association between post-transplant microbiota and patient outcomes, Dr. Taur and a team of researchers collected fecal specimens from 80 patients undergoing allogeneic SCT and sequenced each sample’s bacterial DNA. Specimens were collected within seven days of engraftment, the point at which transplanted blood-forming cells start to grow and make healthy cells in the recipient and the point at which researchers speculated that microbiota diversity would be greatest following pre-transplant conditioning.

Researchers compared patient outcomes based on diversity of microbiota in their specimens, grouping subjects into high, intermediate, and low microbiota diversity categories. At time of stem cell engraftment, 34 patients (42.5%) were observed to have low gut microbiota diversity, 20 (25%) of patients had intermediate diversity, and 26 (32.5%) patients had high diversity. The analysis continued for up to three years or until death or last follow-up.

Following their analyses, researchers found a strong connection between post-transplant gut microbiota diversity and outcomes, observing overall survival rates of 36 percent, 60 percent, and 67 percent among the low, intermediate, and high diversity groups, respectively. Furthermore, researchers observed that diversity was particularly associated with transplant-related outcomes, concluding that patients with low microbiota diversity were approximately five times more likely to die of transplant-related causes within the follow-up period than those with more diverse gut bacteria.

“These results further underscore the significance of the gut microbiota in allogeneic stem cell transplant. A major question is whether we can improve outcomes by preserving diversity within the gut microbiota,” said Dr. Taur.    “One possible strategy is to find ways to perform transplants in a manner that minimizes damage to the gut microbiota. Another approach would be to replenish the gut with beneficial microbes that are lost after this procedure is performed. We hope that this study will inspire additional research that will further examine the role and importance of the gut microbiota to stem cell transplant outcome.”

Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.

ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.

blood® is a registered trademark of the American Society of Hematology.

SOURCE American Society of Hematology

and for full article:

http://news.yahoo.com/gut-bacteria-predict-survival-stem-cell-transplant-study-140000698.html?soc_src=copy