Author Interviews, Microbiome, Nature, NYU/NYMC, OBGYNE / 01.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21187" align="alignleft" width="150"]Maria Dominguez-Bello, PhD Associate Professor, Department of Medicine, Division of Translational Medicine NYU Langone Medical Center Dr. Dominguez-Bello[/caption] Maria Dominguez-Bello, PhD Associate Professor, Department of Medicine, Division of Translational Medicine NYU Langone Medical Center and [caption id="attachment_21188" align="alignleft" width="150"]Jose Clemente, PhD Assistant Professor, Departments of Genetics and Genomic Sciences, and Medicine Icahn School of Medicine at Mount Sinai Dr. Jose Clemente[/caption] 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.
Author Interviews, JAMA, OBGYNE, Pediatrics / 11.01.2016

MedicalResearch.com Interview with: Annie Gatewood Hoen, PhD  Assistant Professor of Epidemiology and of Biomedical Data Science and Juliette Madan, MD, MS Associate Professor of Pediatrics The Geisel School of Medicine at Dartmouth Dartmouth-Hitchcock Medical Center Lebanon, NH 03756 Medical Research: What is the background for this study? What are the main findings? Response: When newborns are delivered they begin the process of acquiring vast numbers of bacteria that are critical for healthy nutrition and for immune training for a lifetime of health. Diseases such as obesity, heart disease, colitis, autism, and even cancer risk is associated with particular patterns in the gut microbiota; interestingly breast milk exposure is associated with decreased risk of many of these diseases. The intestinal microbiome plays a critical role in development, and delivery mode (cesarean section versus vaginal delivery) and feeding method (breast milk vs. formula) are important determinants of microbiome patterns.  We observed the intestinal microbiome in 6 week old infants and how it relates to delivery type and feeding. We were particularly interested in examining patterns in the microbiome in infants who received combination feeding of both breast milk and formula, an area that has been understudied. We prospectively studied 102 infants and, with gene sequencing of bacteria, identified important patterns in microbiome composition that differed greatly based upon delivery method and between feeding groups.  Babies who were combination fed (formula and breast milk) had an intestinal microbiome that was more similar to babies who were exclusively formula fed than breast fed babies. We identified individual bacteria that were differentially abundant between delivery mode and feeding groups.
Author Interviews, C. difficile, Hospital Acquired, Infections, Microbiome / 07.01.2016

[caption id="attachment_20480" align="alignleft" width="128"]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 Dr. Casey Theriot[/caption] 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.
Author Interviews, Gastrointestinal Disease, Microbiome / 11.11.2015

[caption id="attachment_19265" align="alignleft" width="200"]Shannon D. Manning, Ph.D., M.P.H. Dept. of Microbiology and Molecular Genetics Michigan State University E. Lansing, MI 48824 Dr. Manning[/caption] 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.
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.
Author Interviews, C. difficile, Gastrointestinal Disease, Mayo Clinic, Microbiome, Transplantation / 22.10.2015

[caption id="attachment_18565" align="alignleft" width="125"]Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic Dr. Sahil Khanna[/caption] 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..
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.
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.
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.
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.
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.
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.
Asthma, Author Interviews, Nature, Nutrition / 01.07.2015

Dr. Alison Thorburn Ph.D. School of Medical and Applied Sciences, Central Queensland University Rockhampton, Queensland 4702, AustraliaMedicalResearch.com Interview with: Dr. Alison Thorburn Ph.D. Department of Immunology Monash University Victoria, Australia Medical Research: What is the background for this study? Dr. Thorburn: Asthma is a highly prevalent disease in the Western World. The prevailing explanation for this has been the hygiene hypothesis, which proposes that a decline in family size and improved hygiene has decreased exposure to infectious agents and therefore resulted in dysregulated immune responses that lead to asthma. However, recently there has been more attention on the role of diet and the gut microbiota in explaining the prevalence of inflammatory diseases in Western World. Indeed, many studies implicate obesity, as well as a high fat, low fruit and vegetable diet with higher prevalence of asthma. On the other hand, a Mediterranean diet, which is high in fruit and vegetables, is associated with lower prevelance of asthma. Interestingly, the consumption of dietary fiber is reduced in severe asthmatics. These and other data suggest that the diet (particularly dietary fibre) and the gut microbiota may play an important role in the development of asthma. Medical Research: What are the main findings? Dr. Thorburn: The main findings of this study are that: -        In mice: A high-fiber diet promotes a gut microbiota that produces high levels of anti-inflammatory short-chain fatty acids (SCFAs), particularly acetate. Acetate (alkaline form of vinegar) suppressed the development of allergic airways disease (AAD, a model for human asthma) in adult mice and the offspring of pregnant mice. -        In humans: High dietary fiber intake during late pregnancy is associated with higher acetate levels in the serum and a decrease in the percentage of infants showing predictors for asthma development in later life. -        The mechanism underlying these findings involves increasing T regulatory cell number and function through epigenetic mechanisms, which enhance immune regulation to prevent inflammation.
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.
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.
Allergies, Author Interviews, Infections, Microbiome / 27.03.2015

Vijay R. Ramakrishnan, MD Assistant Professor University of Colorado Department of Otolaryngology Aurora, CO 80045MedicalResearch.com Interview with: Vijay R. Ramakrishnan, MD Assistant Professor University of Colorado Department of Otolaryngology Aurora, CO 80045 Medical Research: What is the background for this study? What are the main findings? Dr. Ramakrishnan: Chronic rhinosinusitis (CRS) is an extremely common problem, associated with major quality of life alterations and financial burden. Bacteria are thought to play a role in the initiation or sustenance of the disease, at least in a subset of CRS patients. Chronic rhinosinusitis is probably a group of heterogeneous diseases with different pathways that result in the same endpoint. Here, we study the bacterial microbiome of a large group of CRS and healthy sinuses, and discover that a few clinical subtypes display unique bacterial microbiome profiles and that the microbiome may predict outcomes from severe Chronic rhinosinusitis patients electing to undergo surgery.
Allergies, Microbiome / 23.02.2015

Christine Cole Johnson, PhD, MPH Senior Staff Epidemiologist & Henry Ford Distinguished Scientist Department Chair Department of Public Health Sciences Henry Ford Hospital and Health System Detroit MichiganMedicalResearch.com Interview with: Christine Cole Johnson, PhD, MPH Senior Staff Epidemiologist & Henry Ford Distinguished Scientist Department Chair Department of Public Health Sciences Henry Ford Hospital and Health System Detroit Michigan   Medical Research: What is the background for this study? What are the main findings? Dr. Johnson: Our research group is focused on the environmental and infant gut microbiomes. We are interested in studying what environmental, lifestyle and behavioral factors affect the microbial community of the baby's gastrointestinal tract, and how that microbial community composition affects the development of allergic disorders. We have been following a birth cohort called WHEALS in Detroit and its suburbs since 2003, collecting data on potential risk and preventive factors as well as environmental samples and stool samples from the babies. We have used sequencing of the v4 region of the 16s rRNA gene, common and unique to all bacteria, to develop a fingerprint of the bacterial community in the stool samples. We have found that many variables shown in the past by ourselves and others to allergic disorders are associated with different types of bacterial communities, such as breastfeeding, mode of delivery, first born status, socioeconomic status, pets in the home, levels of endotoxin in the home, and environmental tobacco smoke. Current breastfeeding is the most important variable at both 1 and 6 months, and at one month, mode of delivery is next most important. Endotoxin levels in house dust samples, a crude marker of bacteria levels, are important at 1 month but even more important at 6 months. We also found that certain bacterial community patterns in the baby's gut impact whether or not they have parental-reported allergic symptoms when exposed to cats and dogs when the children are about 4 years of age.