Common Bacteria May Be One Cause of Type II Diabetes

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.

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Gut Bacteria in Infancy May Have Long Lasting Effects on Weight

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.

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An Improved Test for Creutzfeldt-Jakob Disease

Byron Caughey, PhD Senior Investigator Rocky Mountain Laboratories National Institute for Allergy and Infectious Diseases National Institutes of Health Hamilton, Montana 59840MedicalResearch.com Interview with:
Byron Caughey, PhD
Senior Investigator
Rocky Mountain Laboratories
National Institute for Allergy and Infectious Diseases
National Institutes of Health
Hamilton, Montana 59840

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Caughey: One of the challenges in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases such as Creutzfeldt-Jakob disease (CJD) because the causative prion agents are deadly, transmissible and unusually resistant to decontamination. A recently developed test called Real-Time Quaking-Induced Conversion (RT-QuIC) allows for highly sensitive and specific detection of Creutzfeldt-Jakob disease using human cerebrospinal fluid (CSF) or nasal brushings and is being widely implemented as a key diagnostic tool. However, the currently implemented CSF-based test takes 2.5-5 days and misses 11-23% of Creutzfeldt-Jakob disease cases. We have now markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced analytical and diagnostic sensitivity. Analysis of 11 Creutzfeldt-Jakob disease patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples sporadic Creutzfeldt-Jakob disease patients were positive while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Caughey: Our improved RT-QuIC assay should allow for much faster, more accurate and practical testing for Creutzfeldt-Jakob disease using patients’ CSF samples.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Caughey: Future studies should be aimed at further evaluating the diagnostic utility of the RT-QuIC test using much larger numbers of CSF specimens and additional diagnostic centers. In a larger sense, the RT-QuIC assay provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer’s, Parkinson’s and tauopathies.

Citation:

Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid.

Orrú CD, Groveman BR, Hughson AG, Zanusso G, Coulthart MB, Caughey B.

mBio. 2015 Jan 20;6(1). pii: e02451-14. doi: 10.1128/mBio.02451-14.

MedicalResearch.com Interview with:, Byron Caughey, PhD, Senior Investigator, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, & Hamilton, Montana 59840 (2015). An Improved Test for Creutzfeldt-Jakob Disease MedicalResearch.com

Urinary Detection of Prions That Cause Creutzfeldt-Jakob Disease

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 1×10^-16 g/ml, or 3×10^-21 moles/ml, which extrapolates to ~40-100 particles per ml of urine.
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Bacterial Mix Important For Intestinal Health

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.
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Recalled Yogurt Harbored Harmful Fungus

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.
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