Author Interviews, Diabetes, mBio, Microbiome / 04.06.2015

Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242MedicalResearch.com Interview with: Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242 Medical Research: What is the background for this study? Dr. Schlievert:
  1. As people become obese and enter pre-diabetes type II, there is a gut microbiome shift in bacteria from Bacteroidetes to Firmicutes. A dominant pathogenic Firmicute in humans is Staphylococcus aureus.
  2. As people become obese, their skin becomes wetter due to enhanced sweating upon exertion and the presence of more skin folds. These, plus mucous membranes have enhanced Staphylococcus aureus numbers, such that 100% of people become colonized and numbers of the bacterium rise to 1013 per person. This number of bacteria is like a cubic inch of margarine spread across the skin and mucous membranes.
  3. All pathogenic Staphylococcus aureus bacteria make and secrete a family of toxins called superantigens, including toxic shock syndrome toxin and staphylococcal enterotoxins. In high amounts (0.1 μg/human), these toxins can be lethal, causing toxic shock syndrome. At lower concentrations, the same superantigen toxins cause total body inflammation without lethality.
  4. In order to show that a microbes causes human disease, it is necessary to fulfill Koch’s postulates:
    1. Must associate human symptoms with a particular disease,
    2. Must isolate a potentially causative bacterium that is always present when the disease is present.
    3. Must produce the disease in an experimental animal.
    4. Must re-isolate the microbe from the experimental animal and re-cause the disease in another animal.
Medical Research: What are the main findings? Dr. Schlievert: We have fulfilled Koch’s postulates, showing that Staphylococcus aureus and its superantigen toxins cause type II diabetes.
Author Interviews, Gastrointestinal Disease, mBio, Weight Research / 06.02.2015

Senior Principal Investigator - Systems Biology Singapore Institute for Clinical Sciences Brenner Centre for Molecular Medicine SingaporeMedicalResearch.com Interview with: Joanna Holbrook PhD Senior Principal Investigator - Systems Biology Singapore Institute for Clinical Sciences Brenner Centre for Molecular Medicine Singapore Medical Research: What is the background for this study? Dr. Holbrook: Bacteria in the human gut may influence many aspects of our health; however, it is not fully known what determines the composition of the gut microbiota. Rapid bacterial colonisation of the infant gut could be influenced by the environment of the baby before birth, and microbiota content has been associated with the development of obesity and insulin resistance. Medical Research: What are the main findings? Dr. Holbrook: The rate of bacterial colonisation of the gut is influenced by external factors such as the method of delivery and duration of gestation. Also, infants with a mature gut bacteria profile at an early age gained normal levels of body fat, while infants with less mature gut bacteria profiles displayed a tendency to gain lower levels of body fat at the age of 18 months, indicating that gut bacteria could be related to normal development and healthy weight gain.
Author Interviews, Infections, mBio, NEJM / 07.08.2014

Claudio Soto, PhD Professor of Neurology Director Mitchell Center for Alzheimer's disease and related Brain Disorders University of Texas Medical School at HoustonMedicalResearch.com Interview with: Claudio Soto, PhD Professor of Neurology Director Mitchell Center for Alzheimer's disease and related Brain Disorders University of Texas Medical School at Houston Medical Research: What are the main findings of the study? Dr. Soto: In this study we describe for the first time the highly sensitive detection of prions in human urine, specifically in samples from patients affected by the variant form of Creutzfeldt-Jakob disease (vCJD), which is the disease produced by infection with prions associated with bovine spongiform encephalopathy, also known as mad cow disease. For detection we used the protein misfolding cyclic amplification (PMCA) technique which amplifies the amount of abnormal prion protein in a cyclical manner conceptually analogous to the polymerize chain reaction. We detected prions in 13 of the 14 vCJD cases analyzed, and the only negative was a sample coming from a patient under treatment with a experimental drug injected directly into the brain. No false positive were observed in the more than 200 cases analyzed.  The concentration of abnormal prion protein in urine was estimated at 1x10^-16 g/ml, or 3x10^-21 moles/ml, which extrapolates to ~40-100 particles per ml of urine.
Author Interviews, Gastrointestinal Disease, mBio / 04.08.2014

Dr. Sridhar Mani MD Departments of Genetics and Medicine Albert Einstein College of Medicine, Bronx, NY 10461MedicalResearch.com Interview with: Dr. Sridhar Mani MD Departments of Genetics and Medicine Albert Einstein College of Medicine Bronx, NY 10461

  Medical Research: What are the main findings of the study? Dr. Mani: In a series of studies using cells grown in the lab and mouse studies, the researchers found that a metabolite called indole 3-propionic acid (IPA)—produced exclusively by so-called commensal bacteria —both strengthens the intestinal epithelium’s barrier function and prevents its inflammation by activating an orphan nuclear receptor, Pregnane X Receptor (PXR). Specifically, PXR activation suppresses production of an inflammatory protein called tumor necrosis factor alpha (TNF-á) while increasing levels of a protein that strengthens the junctions between intestinal epithelial cells (makes the intestines less permeable to noxious substances). Loss of PXR protein and/or IPA results in a disrupted intestinal barrier and increased propensity towards intestinal inflammation and/or toxin induced injury to the intestines.
Author Interviews, Infections, mBio / 08.07.2014

Soo Chan Lee, PhD Senior Research Associate, Center for Microbial Pathogenesis, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, N.C. 27710MedicalResearch.com Interview with: Soo Chan Lee, PhD Senior Research Associate, Center for Microbial Pathogenesis, Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, N.C. 27710 Medical Research: What are the main findings of the study? Dr. Soo Chan Lee: Mucor circinelloides strain isolated from recalled Chobani yogurt was found to be the most virulent subspecies M. circinelloides forma circinelloides that is commonly associated with human infections. When mice were infected with this fungus through the tail-vein, 80% mortality was observed 5 days post infection. When mice were fed with spores, the fungus survived passage through the GI tract as many as 10 days, indicating the fungus can colonize to cause infections.  Whole genome sequence analysis revealed the possibility that this fungus could produce harmful secondary metabolites that are unknown in this fungal species.