Author Interviews, Cancer Research, Inflammation, Microbiome, PLoS, UCLA / 15.04.2016

MedicalResearch.com Interview with: Robert H. Schiestl PhD Department of Environmental Health Sciences, Fielding School of Public Health, Department of Pathology Department of Radiation Oncology Geffen School of Medicine University of California Los Angeles, Los Angeles, California Medical Research: What is the background for this study? What are the main findings? Dr. Schiestl: When we moved from Harvard to UCLA 13 years ago, after 6 years at UCLA our Atm mouse colony lived significantly 4 fold longer and the frequency of DNA deletions was 4.5 fold reduced and the latency of lymphoma 2.5 fold different. Ultimately we identified the reason behind this as a difference in the intestinal bacteria. The Atm deficient mice are hypersensitive to inflammation and the bacteria reduced inflammation. Then I isolated the most prevalent bacterium among the health beneficial bacteria and this bacterium by itself called Lactobacillus johnsonii 456 reduced genotoxicity and all markers of inflammation. (more…)
Author Interviews, Microbiome, Multiple Sclerosis / 05.04.2016

MedicalResearch.com Interview with: Professor JF Cryan PhD Department of Anatomy and Neuroscience APC Microbiome Institute University College Cork Cork, Ireland MedicalResearch.com: What is the background for this study? What are the main findings?  Prof. Cryan: Over the past decade there has been an ever growing body of preclinical studies that highlight an essential role of the gut microbiota in many aspects of physiology including and perhps most surprtisingly the brain . Germ-free animals are one useful approach used to establish causality in gut microbiota-brain relationships. This model has been extremely useful in establishing that the microbiota is essential for appropriate stress responsibility, anxiety-like behaviours, neurogenesis, blood-brain barrier function and microglia activity. From these findings we can see that there is a clear cut role for the microbiota in CNS developmental processes. Here we wanted to investigate using next generation sequencing, as we had done previously in the amygdala what impact life without microbes has on transcriptional regulation in the prefrontal cortex, a brain region essential in many aspects of emotional behaviour. What we uncovered from this was that there was a large number of dysregulated genes in germ-free animals that have a direct role in myelination. We found increased expression levels of genes that encode for structural proteins that are key in forming the myelin sheath. We followed up this finding with transmission electron microscopy to identify whether this marked increase in myelin related gene expression was functional at a structural level. What we found was germ-free myelinated axons in the prefrontal cortex were hypermyelinated (lower g-ratio), they had thicker myelin sheaths compared to conventionally raised mice. Additionally we also had germ-free colonized animals, animals that were born germ-free but have been colonized with a conventional microbiome early in life. These animals displayed no change in myelin related gene expression and appeared to be indistinguishable from the conventional animals. However, at the protein levels they appeared to have increased myelin protein like germ-free mice. This could be due to the fact that these mice were germ-free for at least 3 weeks of life and the hypermyelinated axons had already been established before colonization. Really this shows that we can still target the microbiota in later life that can have an impact of myelin gene regulation. (more…)
Addiction, Dental Research, Microbiome, NYU, Smoking / 30.03.2016

MedicalResearch.com Interview with: Jiyoung Ahn, PhD, RD, MS Associate Professor of Population Health Associate Director of Population Sciences, NYU Perlmutter Cancer Center  and Brandilyn Peters (post-doctoral fellow, lead author) NYU Langone School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Oral bacteria play important roles in oral health, and can influence the health of other body systems as well. We were interested in studying how cigarette smoking affects oral bacteria. To do this, we examined the oral bacteria in mouthwash samples from 112 current smokers, 571 former smokers, and 521 people who never smoked. We found that the mouth bacterial composition of current smokers differed dramatically from those who never smoked. However, the mouth bacterial composition of former smokers was similar to that of never smokers, suggesting that quitting can restore the oral bacteria back to a healthy state. (more…)
Author Interviews, Microbiome / 30.03.2016

MedicalResearch.com Interview with: Jonas Schluter, DPhil Memorial Sloan Kettering Cancer Center New York City Kirstie McLoughlin Department of Zoology Oxford University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Microbes in our guts perform many important functions for our health. Healthy individuals are inhabited by a complex microbial community. A less diverse community is often a sign of ill health, and can be accompanied by loss of beneficial functions that a normal microbial community provides for the host. We try to understand how such complex communities can persist – after all, competition between microbes could lead to the eradication of slow-growing, but helpful microbes. We built a computer model of the gut that allows us to simulate how the host can actively help such slow microbes, and thereby maintain a healthily diverse microbial community. We show that a mechanism by which the host can achieve such selection is via secretions that help slow growing microbes persist by sticking in place. We propose that the host can change microbiota composition by conveying increased adhesion to disadvantages microbes, for example using mucus molecules and the attached sugars such as fucose. We hypothesise that this might also help explain the secretion of vast amounts of immune system molecules such as immunoglobulin A – perhaps they are not only a way to harm, but also to help certain microbes by anchoring them to the mucus. Indeed, we demonstrate that the host can change the selective effect of increased adhesion by tuning the mucus secretion rate: from beneficial for the adhered microbes at low mucus flow to detrimental at high mucus secretion rates. (more…)
Author Interviews, Dermatology, Microbiome / 09.03.2016

MedicalResearch.com Interview with: Sophie Seite, PhD La-Roche-Posay Dermatological Laboratories Asnières, France MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Seite: These studies were performed in order to confirm the previous results published by H. Kong et al showing that the skin microbiota of atopic dermatitis patients was less diversified and presented an overabundance of S. aureus in comparison to healthy subjects. Because each of us has a specific skin microbiota (huge inter-individual variation) we performed an intra-individual design protocol in order to compare the microbiome of a lesional skin area to those of a non-lesional adjacent area. This strategy showed that the skin diversity in AD patients was reduced in non-lesional area and even more in lesional area and that not only Staphylococcus aureus is overabundant but also Staphylococcus epidermidis and Staphylococcus haemolyticus. Furthermore, for the first time the effect of a topical treatment on the skin microbiome was evaluated. Prebiotic strategies using thermal spring water or biomass lysate of nonpathogenic bacteria demonstrated their efficiency for a long term management of AD patients through an action on the skin microbiome. (more…)
Author Interviews, Gastrointestinal Disease, Lancet, Microbiome, Pediatrics / 09.03.2016

MedicalResearch.com Interview with: Phillip I. Tarr, MD Melvin E. Carnahan MD Professor of Pediatrics Director, Pediatric Division of Gastroenterolgy and Nutrition Washington University in St Louis School of Medicine St Louis, MO 63110, USA MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Tarr: There is a longstanding belief that gut bacteria are relevant to the developing necrotising enterocolitis (NEC). We have established dysbiosis in the gut before NEC occurs, suggesting this ecological perturbation might be causal.

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Abuse and Neglect, BMJ, Imperial College, Microbiome, OBGYNE / 23.02.2016

MedicalResearch.com Interview with: Dr. Aubrey Cunnington Faculty of Medicine, Department of Medicine Clinical Senior Lecturer Imperial College, London Medical Research: What is the background for this study? What are the main findings? Dr. Cunnington: We noticed that increasing numbers of women who were having Caesarean section deliveries at our hospitals were requesting for their vaginal fluid to be swabbed onto their babies after birth – a process often termed “vaginal seeding”. The idea behind this, is that it transfers all the natural bacteria (microbiota) from the mother’s vagina to the baby. We know that early on in life, babies born by Caesarean section have different bacteria living on their bodies and in their guts to those of babies born by vaginal delivery. Some people think these differences in the microbiota may be responsible for differences in long-term health, although a causal link is unproven. The hope is that vaginal seeding might reduce the risk of the baby developing some diseases like obesity and asthma in the future. Unfortunately we are a long way from having the evidence to show that this is possible, and we do not know whether vaginal seeding is really safe. Babies born by elective Caesarean section are at lower risk of transfer of some potentially harmful bacteria and viruses from the birth canal, but these harmful bacteria and viruses could be transferred to the baby on a swab and potentially cause a devastating infection. MedicalResearch.com Editor's note:  'Vaginal Seeding' is also known as "microbirthing",    (more…)
Author Interviews, Microbiome, Nutrition, Pediatrics, Weight Research / 12.02.2016

MedicalResearch.com Interview with Tine Rask Licht, Professor Head of Research Group on Gut Microbiology and Immunology Technical University of Denmark National Food Institute Søborg Medical Research: What is the background for this study? What are the main findings? Response:  During childhood, the intestinal microbiota is under establishment. This period thus represents a ’window’, where the microbiota is likely to be more susceptible to be affected by external factors such as diet. Currently, it is well known that breast feeding has a major impact on the microbiota of young infants, but only very few studies have addressed the effect of the ‘next step’ in diet exposure, represented by complementary feeding. We studied two cohorts of children, born to normal-weight and obese mothers, respectively, and mapped the composition of bacteria in their fecal microbiota at age 9 months and 18 months.  We found that at 9 months, the microbiota was clearly affected by the composition of the complementary diet, but not by maternal obesity. (more…)
Author Interviews, Microbiome, Nature, NYU, OBGYNE / 01.02.2016

MedicalResearch.com Interview with: Maria Dominguez-Bello, PhD Associate Professor, Department of Medicine, Division of Translational Medicine NYU Langone Medical Center and Jose Clemente, PhD Assistant Professor, Departments of Genetics and Genomic Sciences, and Medicine Icahn School of Medicine at Mount Sinai       Medical Research: What is the background for this study? What are the main findings? Response: Humans and animals are a composite of their own cells and microbes. But where they get their microbes from?  For mammals, labor and birth are major exposures to maternal vaginal bacteria, and infants are born already with a microbiota acquired from the mother. Mom’s birth canal is heavily colonized by bacteria that are highly related to milk: some will use milk components and become dominant during early development, an important window for maturation of the immune system, the intestine and the brain. Thus, the maternal vaginal microbiota is thought to be of high adaptive value for newborn mammals. Indeed, studies in mice confirm that microbes acquired at birth are important to develop adequate immune and metabolic responses, and the mature adult microbiome will continue to modulate host metabolism and immunity. Humans are the only mammals that interrupt the exposure to maternal vaginal microbiota, by delivering babies by Cesarean section. C-sections save lives of babies and moms, and they are estimated necessary in 10-15% of the cases. But most Western countries have rates above 30%, with the notable exception of the Scandinavian countries, Holland and Japan, which have excellent health systems and low maternal-infant mortality rates. Previous work by us an others has shown that infants born by C-section acquire different microbiota at birth, and those differences are sustained over time, altering the normal age-dependent maturation of the microbiome. The fundamental questions are then, can we restore the microbiota of Cesarean delivered babies? And if we can, does that reduce the associated disease risks? In relation to the first question, we present here the results of a pilot study in which infants born by Cesarean delivery were exposed to maternal vaginal fluids at birth. A total of 18 infants were recruited for the study. Seven of them were vaginally delivered, the remaining 11 were born by scheduled C-section. Among the C-section infants, 4 were exposed to maternal vaginal fluids at birth and 7 were not. We sampled all infants and their mothers for the first month of life across different body sites (oral, skin, anal, maternal vagina) and determined the microbiome composition on a total of over 1,500 samples. (more…)
Author Interviews, C. difficile, Hospital Acquired, Infections, Microbiome / 07.01.2016

MedicalResearch.com Interview with: Casey M. Theriot, Ph.D. Assistant Professor Infectious Disease College of Veterinary Medicine Department of Population Health and Pathobiology North Carolina State University Raleigh, NC 27607 Medical Research: What is the background for this study? What are the main findings? Dr. Theriot: This study is an extension of the work we did in 2014 in our Nature Communications paper (Theriot et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, 2014). We really wanted to know how different antibiotics that varied in their mechanism of action altered the gut microbiota in different ways and also in turn how this altered the bile acids present in the small and large intestine of mice. Primary bile acids are made by the host and are further converted to secondary bile acids by members of the microbiota in the large intestine. We know from previous work that secondary bile acids can inhibit the growth of C. difficile, but no one has looked in depth at the bile acid makeup in the actual gut before in the context of C. difficile. In this study we show that specific antibiotics that significantly alter the large intestinal gut microbiota and deplete all secondary bile acids allow for C. difficile to grow without any inhibition. We also showed that C. difficile spores are always germinating in the small intestine, which means in order to prevent this pathogen from colonizing the gut, we will have to target the growth of the pathogen. Moving forward the focus will be on trying to repopulate the gut with bacteria that are capable of restoring the secondary bile acid pools in order to inhibit C. difficile. (more…)
Author Interviews, Infections, JAMA, Microbiome / 24.12.2015

MedicalResearch.com Interview with: Tara F Carr, MD Assistant Professor, Medicine and Otolaryngology Allergy and Immunology Fellowship Training Program Director Director, Adult Allergy Division of Pulmonary, Allergy, Critical Care and Sleep Medicine University of Arizona Tucson, AZ 85724 Medical Research: What is the background for this study? What are the main findings? Dr. Carr: Some patients with chronic rhinosinusitis continue to suffer from symptoms despite aggressive medical and surgical treatments. For these individuals, therapy is generally chosen based on bacterial culture results, and often includes the use of topical antibacterial rinses with a medication called mupirocin.  We found that if patients are still having problems after this treatment, the bacteria identified from repeated sinus cultures are very different than those usually expected, and in general more difficult to treat. (more…)
Author Interviews, Microbiome, Weight Research / 28.11.2015

MedicalResearch.com Interview with: Dr. Eran Elinav PhD Immunology Department and Prof. Eran Segal PhD Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot , Israel Medical Research: What is the background for this study? Response: Obesity and diabetes are rising epidemics, affecting a significant portion of the world’s population. Blood glucose levels are a major contributor to these epidemics, as they are associated with obesity and with risk to develop diabetes. Normalizing blood glucose can have highly beneficial effects on the health of individuals. Therefore, we decided to study the factors that affect blood glucose. Among these factors are the macro- and micronutrient content of the meal, a person’s lifestyle, medical state, and their microbiome. We then started collecting from participants these exact parameters, and studied their effect on blood glucose. We managed to successfully predict the blood glucose response of many people to many meals and to assign for people beneficial diets based on this prediction. (more…)
Author Interviews, Gastrointestinal Disease, Microbiome / 11.11.2015

MedicalResearch.com Interview with: Shannon D. Manning, Ph.D., M.P.H. Dept. of Microbiology and Molecular Genetics Michigan State University E. Lansing, MI 48824 Medical Research: What is the background for this study? What are the main findings? Dr. Manning: Diarrheal disease is a leading cause of morbidity and mortality in children under the age of five and is commonly caused by many different bacterial pathogens. We have observed that infection with four different bacterial pathogens (Salmonella, Shigella, Shiga toxin-producing E. coli, and Campylobacter) all induce the proliferation of a population of microbes, namely Escherichia, which are already present in the gut of healthy individuals. (more…)
Author Interviews, Cancer Research, Microbiome / 04.11.2015

MedicalResearch.com Interview with: Simba Gill Ph.D CEO, Evelo Therapeutics MedicalResearch: Evelo Therapeutics, a new company focuses on leveraging the power of the microbiome to develop novel therapies for cancer. Evelo is pioneering Oncobiotic™ therapeutics, a new modality in cancer therapy based on the cancer microbiome. Dr. Gill, CEO of  Evelo Therapeutics began his career at Celltech, focused on antibody research. Dr. Gill earned his Ph.D. from King’s College, London, and his MBA from INSEAD. Medical Research:  What is a microbiome? How do microbiomes play a role in health and disease? Dr. Gill: The microbiome is the collection of trillions of bacteria, funguses, viruses and other microbes that live on and within the human body. There are different clusters of microbes in different parts of the body, including the skin, mouth, large intestine, and vagina. Recently we have learned that our microbial populations shift depending on changes to an individual’s health and wellness. The makeup of one’s microbiome has a strong influence on one’s health, immune response, and metabolic state. (more…)
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015

MedicalResearch.com Interview with: Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83.. (more…)
Author Interviews, Eating Disorders, Microbiome / 06.10.2015

Dr. Ian Carroll, PhD Professor of medicine UNC Center for Gastrointestinal Biology and DiseaseMedicalResearch.com Interview with: Dr. Ian Carroll, PhD Professor of medicine UNC Center for Gastrointestinal Biology and Disease  Medical Research: What is the background for this study? What are the main findings? Dr. Carroll: Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme weight dysregulation and presents with high rates of comorbid anxiety.Anorexia nervosa carries the highest mortality rate of all psychiatric illnesses and relapse is frequent. Although a prime contributor, genetic factors do not fully account for the etiology ofAnorexia nervosa, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from Anorexia nervosa. Our study provides evidence of an intestinal dysbiosis in AN and an association between mood and the enteric microbiota in this patient population. (more…)
Author Interviews, BMJ, Heart Disease, Mediterranean Diet, Microbiome, Nutrition, Vegetarians / 29.09.2015

Prof. Danilo Ercolini, PhD Department of Agricultural Sciences University of Naples Federico II Portici - ItalyMedicalResearch.com Interview with: Prof. Danilo Ercolini, PhD Department of Agricultural Sciences University of Naples Federico II Portici - Italy Medical Research: What is the background for this study? What are the main findings? Prof. Ercolini: There is a thick body of literature showing that diet can significantly impact the gut microbiota and metabolome. In a recent study, negligible differences in gut microbiota and feca lshort-chain fatty acids (SCFA) were reported between habitual omnivores and vegans in the USA. In addition, Mediterranean diet is a recognized healthy dietary pattern but has not previously been related to the composition of the gut microbiota and related metabolome. That’s the background in short. Here we show how habitual vegetarian and vegan diets promote enrichment of fibre-degrading bacteria in the gut. Subjects who consume a Mediterranean diet rich in fruit, legumes and vegetables have higher levels of fecal short chain fatty acids, regardless of the diet type. Low adherence to the Mediterranean diet corresponds to an increase in urinary trimethylamine oxide levels, a potential risk factor for cardiovascular disease. (more…)
AHA Journals, Author Interviews, Gastrointestinal Disease, Heart Disease, Microbiome / 16.09.2015

Jingyuan Fu, Ph.D. Associate professor of genetics University Medical Center Groningen NetherlandsMedicalResearch.com Interview with: Jingyuan Fu, Ph.D. Associate professor of genetics University Medical Center Groningen Netherlands  Medical Research: What is the background for this study? What are the main findings? Dr. Jingyuan Fu: Abnormal blood lipid levels are important risk factors for cardiovascular diseases. Because of that, a common advice is to have a healthy lifestyle or take lipid-lowering drugs like statin to control the blood lipid level. However, the problem is only partially solved. Cardiovascular disease remains the No 1 cause of death globally, representing 31% of all global deaths.  The primary purpose of the study is to look for a new solution in humans’ gut. Over millions of years, microbes and humans have formed a truly symbiotic relationship. Human body contains 10 trillion bacteria, 10x more than human cells. They help digest food and train our immune systems. As less than 30% of bacteria in human gut can be cultured, we know very little how they are and what they do in our gut. With the state-of-art deep sequencing technology, we are now able to see who are there. The research questions would be how much effect these bacteria could affect the blood lipids levels and which bacteria play important role. No such an analysis was done in large-scale human population. Our study was the first to provide solid evidence for the associations between gut bacteria and blood lipids. Although we cannot conclude cause-effect relationship yet, it serves an important step in narrowing possible therapeutic targets. (more…)
Allergies, Asthma, Author Interviews, Microbiome, Pulmonary Disease / 28.08.2015

Rebecca Normansell MA MB BChir Cochrane Airways Population Health Research Institute St George’s, University of London MedicalResearch.com Interview with: Rebecca Normansell MA MB BChir Cochrane Airways Population Health Research Institute St George’s, University of London     Medical Research: What is the background for this study? Response: Asthma is a common, long-term, respiratory condition which affects over 300 million people worldwide. It is a burden not only for the individual with asthma but also for the health services that care for them and the wider economy, due to days lost from work and school. Asthma therapies aim to prevent attacks and improve symptoms by reducing airway constriction and inflammation, but they come with their own risks of side effects. For example, long-term high-dose inhaled corticosteroids have been associated with growth restriction in children and long-acting beta2-agonists as mono-therapy have been associated with increased risk of death in people with asthma. There is growing interest in developing novel treatments for asthma and one such treatment is specific allergen immunotherapy. Immunotherapy has the potential to be a useful approach for asthma as it is thought that for approximately half of people with asthma, allergies are an important trigger for their symptoms and attacks. Immunotherapy can be delivered by injection (subcutaneously) or under the tongue (sublingually) and aims to bring about immune tolerance. Immunotherapy has already been demonstrated to be effective in certain conditions, such as allergic rhinitis and wasp and bee sting allergy, but its effectiveness and safety in asthma is less clear. In fact, immunotherapy is not recommended at all for use in people with severe or uncontrolled asthma due to the risk of triggering a serious respiratory reaction. Medical Research: What are the main findings? Response: Our review looked for trials in which people with asthma who were given sublingual immunotherapy (SLIT) were compared with those given placebo, or who continued usual asthma care. We found 52 randomised controlled trials which met our inclusion criteria, allocating over 5,000 people to either SLIT or placebo/usual care. Most of the participants had mild asthma and were allergic to either house dust mite or pollen. Despite the large number of eligible trials we were only able to perform a limited meta-analysis. This is because most of the trials did not report the efficacy outcomes we were most interested in: exacerbations and quality of life. Asthma symptoms and medication use were both more frequently reported, but often using different, un-validated scales so we did not perform a meta-analysis for these outcomes. However, we were able to combine serious adverse event data from 22 trials involving 2560 participants and data for all adverse events from 19 trials including 1755 participants. SLIT did not appear to be associated with an increased risk of serious adverse events, although very few events were observed overall. SLIT was associated with a small increase in the risk of all adverse events, which in absolute terms equated to an increase from 222 per 1000 people in the control group to 327 per 1000 (95% confidence intervals 257 to 404). Importantly, many of these events were mild and transient local reactions and did not generally result in participants withdrawing from the trial. (more…)
Author Interviews, Mental Health Research, Microbiome / 26.08.2015

Keith A. Crandall, PhD Director - Computational Biology Institute George Washington University Innovation Hall Suite 305 Ashburn, VA 20147-2766MedicalResearch.com Interview with: Keith A. Crandall, PhD Director - Computational Biology Institute George Washington University Innovation Hall Suite 305 Ashburn, VA 20147-2766 Medical Research: What is the background for this study? What are the main findings? Dr. Crandall: We wanted to investigate whether or not there were significant differences in the microbiome (microbial composition) of patients with schizophrenia versus controls.  The other researchers have demonstrated a connection between microbiome diversity and brain development and behavior modulation associated with a variety of disorders.  Our initial study focuses on the oropharyngeal as a target for the microbiome characterization, but we have additional work relating to other microbiomes (e.g., gut) for which we are still in the process of analyzing the data.     Collected microbiome data from 16 individuals with schizophrenia and 16 controls (matched as best we could and corrected statistically for differences between the populations), we showed differences in the microbiome taxonomic diversity and functional diversity.  Specifically, we identified a significant increase in the number of metabolic pathways related to metabolite transport systems; whereas, carbohydrate and lipid pathways and energy metabolism were abundant in controls. (more…)
Allergies, Asthma, Author Interviews, Microbiome / 14.08.2015

Yvonne J. Huang, MD Assistant Professor, Division of Pulmonary & Critical Care Medicine University of Michigan Health System Ann Arbor, MI 48109-5642 MedicalResearch.com Interview with: Yvonne J. Huang, MD Assistant Professor, Division of Pulmonary & Critical Care Medicine University of Michigan Health System Ann Arbor, MI  48109-5642   Medical Research: What is the background for this study? Dr. Huang: Asthma is a disease with many different clinical manifestations, and it is likely that multiple mechanisms play a role in asthma. Understanding the biological processes that contribute to this heterogeneity is an important goal of current translational research in asthma. One hypothesis that dates back several decades is whether asthma, at least in some forms, is linked to chronic airway infection or colonization by particular species of bacteria.  Results of early investigations in this regard were mixed, in part due to reliance on less sensitive methods to detect bacterial infection, but a new spin on this hypothesis has emerged in recent years.   This stems from the technological advances that now enable one to molecularly profile all bacteria present in a sample, such as via sequence analysis of conserved bacterial genes (such as that for 16S ribosomal RNA). 16S rRNA-based methods are now commonly used to profile bacterial microbiota in a variety of human niches, including in studies of respiratory disease. Prior to our current study, a few investigations had shown that the lower respiratory microbiome in adult asthmatics differs in bacterial composition (i.e. the types and relative abundance of bacteria present), compared to healthy controls.   In a previous study of patients with mild-moderate asthma, we also had found that clinical features of asthma, such as bronchial hyper-responsiveness, were associated with increased abundance of specific bacterial groups.  However, whether similar relationships between clinical features and the  microbiome exist in severe asthma was unknown, which we addressed in the current study. (more…)
Author Interviews, Gastrointestinal Disease, Microbiome, PLoS / 10.07.2015

MedicalResearch.com Interview with: Mashkoor A.  Choudhry, PhD Professor of Surgery, Microbiology & Immunology Burn & Shock Trauma Research Institute Stritch School of Medicine Loyola University Chicago Health Sciences Division Maywood, IL 60153 Medical Research: What is the background for this study? What are the main findings? Dr. Choudhry: Intestine is the major reservoir of bacteria in the body. We observed that gut bacterial composition is altered after burn injury. We found that burn causes a significant increase in Enterobacteriaceae, a group of bacteria that has the potential to be harmful for the host. Dysbiosis of the healthy intestinal microbiome is associated with a number of inflammatory conditions. (more…)
Author Interviews, Microbiome, Weight Research / 30.06.2015

Dr. Karine Clément M.D., Ph.D. Assistant Professor, Nutrition Department Hotel-Dieu hospital ParisMedicalResearch.com Interview with: Prof. Karine Clément MD, PhD Director ICAN - Institute of Cardiometabolism And Nutrition Hôpital La Pitié-Salpêtrière, Paris www.ican.paris [email protected] Medical Research: What is the background for this study? What are the main findings? Dr. Clément: Obesity, associated with insulin resistance, is a chronic inflammatory disease revealed by a moderate but long-term increase in the levels of inflammatory molecules in the blood. Our groups and others have shown that several organs such as adipose tissues, liver, pancreas and muscles are also sites of inflammation with accumulation of immune cells such as macrophages and lymphocytes. This low-grade inflammatory state perturbs the tissue biology and contributes to the development and/or maintenance of insulin resistance and diabetes. In addition our teams and others showed that the intestinal functions are altered in obesity such as sugar and lipid absorption of and enteroendocrine nutrient signaling to the whole body. Our teams showed modifications of immunity in the obese intestine, and particularly in the jejunum part where most of sugar and lipid absorption takes place. Obesity increases the absorptive surface of the intestine and the colonization of the epithelium by CD8αβ T lymphocytes not affecting tissue integrity, thus differing from IBD inflammation. The cytokines secreted by the CD8 T cells of obese, but not lean subjects, are able to inhibit insulin action in enterocytes. In these patients, the increase of intestinal CD8 T cell density correlates with sugar absorption capacity and with the level of obesity and associated complications such as liver disease (NASH – Non-Alcoholic SteatoHepatitis) and dyslipidemia. (more…)
Author Interviews, Infections, Microbiome, Urinary Tract Infections / 29.06.2015

MedicalResearch.com Interview with: Jeffrey P. Henderson, M.D., Ph.D. Assistant Professor of Medicine and Molecular Microbiology Center for Women's Infectious Diseases Research Division of Infectious Diseases and Robin Shields-Cutler, Ph.D Ph.D. Student, Molecular Microbiology and Microbial Pathogenesis Washington University School of Medicine St. Louis, Missouri Medical Research: What is the background for this study? Response: Increasing antibiotic resistance, together with an appreciation that many patients are particularly susceptible to recurrent Urinary Tract Infections UTIs following antibiotic therapy, motivated interest in the events that occur during early stages of UTI pathogenesis. Abundant evidence suggests that uropathogenic E.coli must obtain iron from human hosts in order to cause a clinical infection. Early in infection, human cells secrete a protein called siderocalin that is known to limit bacterial growth by sequestering iron. This protein is detectable in the urine of Urinary Tract Infections patients. Medical Research: What are the main findings? Response: We obtained urine from a diverse panel of healthy volunteers, inoculated them individually with a uropathogenic E.coli strain, and monitored growth in the presence and absence of a fixed amount of siderocalin. Siderocalin exhibited a remarkably wide range of activity between individuals. We traced this variation back to differences in urinary pH and to phenolic urinary metabolites. We could significantly facilitate siderocalin’s antibacterial activity in urine by alkalinizing it above 6.5 and adding phenolic metabolites. The metabolites that potentiate siderocalin’s antibacterial effect have been linked to dietary sources such as coffee, tea, and berries. Some of these compounds may further derive from the actions of gut microbes on dietary phenols. The functional basis for these compounds’ properties seems to arise from siderocalin’s ability to use them as molecular grips that chelate iron ions in a form that is difficult for bacteria to access. From the pathogen perspective, we found that enterobactin, a molecule secreted by E.coli, acts as a microbial countermeasure to urinary siderocalin. Adding a drug-like inhibitor to urine that blocks enterobactin biosynthesis greatly increased siderocalin’s antibacterial effect. (more…)
Author Interviews, BMC, Colon Cancer, Microbiome / 26.06.2015

Michael B. Burns, Ph.D. HHMI Post-Doctoral Fellow Dept. of Genetics, Cell Biology and Development Dept. of Ecology, Evolution, and Behavior Masonic Cancer Center Dept. of Biology Teaching and Learning University of Minnesota, Twin Cities St. Paul, MN 55108MedicalResearch.com Interview with: Michael B. Burns, Ph.D. HHMI Post-Doctoral Fellow Dept. of Genetics, Cell Biology and Development Dept. of Ecology, Evolution, and Behavior Masonic Cancer Center Dept. of Biology Teaching and Learning University of Minnesota Twin Cities St. Paul, MN 55108 Medical Research: What is the background for this study? Dr. Burns: Recent technological advances have made it possible to survey all the of microbes that are in, on, and around us. One of the surprising things is the sheer quantity and diversity of the bacteria in our environments and our microbiomes. Many researchers have begun the systematic characterization of the microbes that are associated with specific disease states, including cancer. With regard to colorectal cancer, there have been numerous studies that have identified specific bacteria that are linked to the presence of the disease. There have been many reports that have identified particular potentially important microbes that may be causing the cancer, driving the cancer, or some combination of the two. Among these microbes, one of the best studied so far is a group of bacteria called Fusobacterium. Medical Research: What are the main findings? Dr. Burns: In our work, we set out to perform another characterization of the bacteria in the gut microbiome that are specifically associated with colorectal tumors. We used samples of normal colon tissue from the same individuals as controls, which allowed us to account for much of the variability in the different bacteria we found that might have been simply the result of, for instance, diet. In our analysis, we confirmed the previous results related to Fusobacterium, and additionally discovered a new potential culprit in colorectal cancer, a group of bacteria named Providencia. The finding of another new set of microbes that might be causing or driving cancer is not surprising. As indicated above, there are many groups who have found other potential candidate microbes that could be implicated in the disease. Our next question was to determine if there was some reason why there might be so many different bacteria that are linked with the disease and what it might be able to tell us about what these bacteria are doing. To that end, we used computational approaches to assess what these two groups of bacteria might be doing at a functional level and if there were any similarities. We found that there was a great deal in common between Fusobacterium and Providencia, including a finding that one of the common functions was related to a large group of virulence genes. (more…)
Author Interviews, Gastrointestinal Disease, Microbiome / 24.06.2015

Kathy Magnusson D.V.M., Ph.D Professor Oregon State College of Veterinary Medicine Principal Investigator with the Linus Pauling InstituteMedicalResearch.com Interview with: Kathy Magnusson D.V.M., Ph.D Professor Oregon State College of Veterinary Medicine Principal Investigator with the Linus Pauling Institute Medical Research: What is the background for this study? Dr. Magnusson: There is increasing evidence that the gut microbiome can communicate with our brain. Others had also shown that high-energy diets could alter the composition of the gut microbiome (i.e., shift the percentages of different bacteria within the population) and could alter cognitive function. We decided to use that dietary model to determine whether there was a relationship between the bacterial changes and the behavioral changes. Medical Research: What are the main findings? Dr. Magnusson: We found decreases in Bacteroidales and increases in Clostridiales orders of bacteria, similar to that seen in obese humans and animals on high energy diets. We also found problems with early learning for long-term memory, with delayed short-term memory and with cognitive flexibility, the ability to adapt to new rules and changing conditions. The alterations in Bacteroidales and Clostridiales showed a relationship to this decline in cognitive flexibility. (more…)
Author Interviews, C. difficile, Columbia, Gastrointestinal Disease, Microbiome, Pediatrics / 19.06.2015

Daniel E. Freedberg, MD, MS Assistant Professor of Medicine Division of Digestive and Liver Diseases Columbia University, New YorkMedicalResearch.com Interview with: Daniel E. Freedberg, MD, MS Assistant Professor of Medicine Division of Digestive and Liver Diseases Columbia University, New York Medical Research: What is the background for this study? Dr. Freedberg: Acid suppression medications are increasingly prescribed to relatively healthy children without clear indications, but the side effects of these medications are uncertain. Medical Research: What are the main findings? Dr. Freedberg: Acid suppression with (proton pump inhibitors ) PPIs or (histamine-2 receptor antagonists) H2RAs was associated with increased risk for C. diff infection in both infants and older children. Medical Research: What should clinicians and patients take away from your report? Dr. Freedberg: Increased risk for C. diff should be factored into the decision to use acid suppression medications in children.  Our findings imply that acid suppression medications alter the bacterial composition of the lower gastrointestinal tract. (more…)
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. (more…)
Author Interviews, Microbiome, Pediatrics / 23.05.2015

MedicalResearch.com Interview with: Ms. Pajau Vangay Graduate Research Fellow Biomedical Informatics and Computational Biology Vice President of Grants, Council of Graduate Students University of Minnesota Medical Research: What is the background for this study? What are the main findings? Response: Previous studies showed links between antibiotic use and unbalanced gut bacteria, and others showed links between unbalanced gut bacteria and adult disease. Over the past year we synthesized hundreds of studies and found evidence of strong correlations between antibiotic use, changes in gut bacteria, and disease in adulthood. (more…)