Author Interviews, C. difficile, Gastrointestinal Disease, Microbiome, Transplantation / 14.03.2017 Interview with: Dr. H. L. DuPont MD Director, Center for Infectious Diseases, UTHealth School of Public Health Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth Professor, Department of Epidemiology, Human Genetics and Environmental Sciences UTHealth School of Public Health Houston, TX 77030 What is the background for this study? What are the main findings? Response: Many diseases and disorders are associated with “dysbiosis,” where the intestinal microbiota diversity is reduced. This contributes to disease and to the acquisition of antibiotic resistance. Fecal microbiota transplantation (FMT) is successful in conditions with pure dysbiosis (e.g. C diff infection) and a single dose of FMT is curative in most cases. (more…)
Author Interviews, Heart Disease, Microbiome, Nutrition, Race/Ethnic Diversity / 23.02.2017 Interview with: Akira Sekikawa, Ph.D. Associate professor of epidemiology University of Pittsburgh Graduate School of Public Health What is the background for this study? What are the main findings? Response: We found that Japanese men who are able to produce equol—a substance made by some types of “good” gut bacteria when they metabolize isoflavones (micronutrients found in dietary soy)—have lower levels of a risk factor for heart disease than their counterparts who cannot produce it. All monkeys can produce equol, as can 50 to 70 percent of people in Asian countries. However, only 20 to 30 percent of people in Western countries can. Scientists have known for some time that isoflavones protect against the buildup of plaque in arteries, known as atherosclerosis, in monkeys, and are associated with lower rates of heart disease in people in Asian countries. It was surprising when a large trial of isoflavones in the U.S. didn’t show the beneficial effects on atherosclerosis. My colleagues and I recruited 272 Japanese men aged 40 to 49 and performed blood tests to find out if they were producing equol. After adjusting for other heart disease risk factors such as high blood pressure, cholesterol, smoking and obesity as well as dietary intake of isoflavones, we found that the equol-producers had 90-percent lower odds of coronary artery calcification, a predictor of heart disease, than the equol non-producers. (more…)
Author Interviews, Gastrointestinal Disease, Infections, Microbiome, Rheumatology, Science / 11.02.2017 Interview with: Randy Longman, M.D. / Ph.D. Assistant Professor of Medicine Jill Roberts Center and Institute for Research in Inflammatory Bowel Disease Weill Cornell Medicine Division of Gastroenterology and Hepatology Joan and Sanford I. Weill Department of Medicine Department of Microbiology and Immunology New York, NY 10021 What is the background for this study? What are the main findings? Response: Inflammatory bowel disease is not limited to intestinal inflammation.  Up to 1/3 of patients with active disease suffer from extra-intestinal manifestations. The most common extra-intestinal manifestations in IBD is joint inflammation or spondyloarthritis.  Peripheral joint spondyloarthritis  carries a prevalence of 20% in Crohn’s Disease and 10% in Ulcerative Colitis, predominantly affecting joints of the lower limbs.  It has long been suggested that gut bacteria can drive this systemic joint inflammation, but microbial targets have not been characterized. (more…)
Author Interviews, Gastrointestinal Disease, Microbiome / 01.02.2017 Interview with: Fernando Azpiroz, MD, PhD Chief of the Department of Digestive Diseases University Hospital Vall d’Hebron Autonomous University of Barcelona, Spain What is the background for this study? What are the main findings? Response: This open-label, single-arm study, included 26 healthy volunteers who did not have gastrointestinal (GI) symptoms or a history of GI disorders, and were not required to change their diets during treatment. Twenty participants were included in the main evaluation and six were included as control subjects. Participants in the main study were given HOST-G904 (2.8 g/day) for three weeks, during which time they followed their usual diet. In the evaluation periods (three-day periods immediately before, at the beginning and at the end of the administration), the participants followed a standardized low-fiber diet with one portion of high-fiber foods, at which time the investigators measured the following: (1) number of daytime gas evacuations for two days; (2) volume of gas evacuated; and (3) microbiome composition (as measured by fecal Illumina MiSeq sequencing). (more…)
Author Interviews, Autism, Brigham & Women's - Harvard, Gastrointestinal Disease, Microbiome / 26.01.2017 Interview with: Maria Rosaria Fiorentino, PhD Assistant Professor at Harvard Medical School Molecular Biologist at Mucosal Immunology and Biology Research Center Massachusetts General Hospital East Charlestown, MA 02129-4404 What is the background for this study? What are the main findings? Response: Autism Spectrum Disorders (ASD) refers to complex neurodevelopmental disorders arising from the interaction of genes and environmental factors. There are no defined mechanisms explaining how environmental triggers can lead to these conditions. One hypothesis based on the gut-brain axis connection suggests that inappropriate antigens trafficking through an impaired intestinal barrier, followed by passage of these antigens through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to the disease. Many Autism Spectrum Disorders children experience co-morbid medical conditions, including gastrointestinal (GI) dysfunctions whose underlying nature is poorly understood. Several clinical observations describe increased intestinal permeability in ASD with often conflicting findings. Permeability to neuroactive food antigens derived from the partial digestion of wheat (gliadorphins) and cow’s milk (casomorphins) has been reported in ASD. However, while evidence of a permeable gut barrier in ASD is increasingly reported, no information is available concerning a similar breach for the BBB. The BBB is a critical line of defense in the Central Nervous System, limiting the access of circulating solutes, macromolecules, and cells that could negatively impact neuronal activity. Dysfunctions of the BBB have been associated with numerous inflammatory neurologic disorders, such as stroke, epilepsy, multiple sclerosis, Parkinson’s and Alzheimer’s disease. (more…)
Author Interviews, Diabetes, JCEM, Microbiome / 20.01.2017 Interview with: Prof Lorenzo Piemonti, MD Professor of Endocrinology Deputy Director, Diabetes Research Institute (SR-DRI) Head, Beta Cell Biology Unit Vita-Salute San Raffaele University, San Raffaele Scientific Institute Milano Italy What is the background for this study? What are the main findings? Response: The potential role of gut inflammation and microbiome is becoming a hot topic in the field of diabetes. Several very recent publications report the presence of intestinal abnormalities associated with autoimmune diabetes in both experimental rodent models and patients. We have previously published that, compared to healthy subjects, patients with type 1 diabetes or at high risk of developing type 1 diabetes shows increased intestinal permeability. Among the factors that may modify the intestinal barrier and impact on its immune activation, the gut microbiota is at present the main suspect. Our study is the first in literature that had the opportunity to analyze the inflammatory profile, the microbiome and their correlation on duodenum biopsies of patients with type 1 diabetes, in comparison with patients with celiac disease and healthy controls. Previous papers pointed out a significant difference in the composition of the stool microflora in subjects with autoimmune diabetes. A major advancement of our work comes from the direct analysis of small intestine, instead of studies on stool samples. In fact, because of their close functional and spatial relationships, as well as a shared blood supply, it is logical to consider the duodenum and the pancreas correlated. We found big differences among the groups: gut mucosa in diabetes shows a peculiar signature of inflammation, a specific microbiome composition and we also discovered a strong association between some analysed inflammatory markers and specific bacteria genera. We think that our data add an important piece to disentangle the complex pathogenesis of type 1 diabetes and more generally of autoimmune diseases. (more…)
Author Interviews, FASEB, Microbiome, OBGYNE, Stanford / 09.12.2016 Interview with: Carlos Simón, M.D., Ph. D. Professor of Obstetrics & Gynecology. Valencia University, Spain Scientific Director, Igenomix SL. Adjunct Clinical Professor, Department of Ob/Gyn, Stanford University, CA Adjunct Professor, Department of Ob/Gyn, Baylor College of Medicine, TX What is the background for this study? What are the main findings? Response: The main findings of this study reside in the concept that the uterine cavity, which has been classically considered as a sterile organ, possess its own microbiome and that the composition of this uterine microbiome have a functional impact on the reproductive outcome of IVF patients. (more…)
Author Interviews, Microbiome, Nature, Weight Research / 03.12.2016 Interview with: Dr. Eran Elinav. Principal investigator Immunology Department Weizmann Institute of Science Rehovot, Israel What is the background for this study? What are the main findings? Response: Recurrent obesity is a very common yet poorly studied and under researched phenomenon. It is well known that many people diet, but then regain the weight they lost and even add more weight. We found that the gut microbiome is a major driver of this enhanced weight regain phenomenon. We found that in the obese state, the microbiome is altered, and these alterations are not reversed upon weight loss. And these alterations are sufficient to drive weight regain, since transferring them to germ-free mice also transferred the enhanced weight regain phenotype. Moreover, we provide three different treatments for this condition: (1) Antibiotics; (2) transfer of bacteria from lean mice; and (3) addition of specific molecules that we found to be lacking in the altered microbiome. All of these treatments cured the mice we tested from enhanced weight regain. (more…)
Author Interviews, Gastrointestinal Disease, Microbiome, Nutrition / 21.11.2016 Interview with: What is the background for this study? Response: Over the last few decades, our intake of dietary fiber has fallen drastically mainly due to the consumption of processed food, which has been connected to increased cases of intestinal diseases including colon cancer and inflammatory bowel disease. The gut microbiota is essential for us as it allows our body to digest dietary fiber contained in fruits and vegetables, that could otherwise not be processed. Changed physiologies and abundances of the gut microbiota following a fiber-deprived diet have been commonly linked to several intestinal diseases. However, the mechanisms behind these connections have remained poorly understood. (more…)
Author Interviews, C. difficile, Microbiome, Nature, Vanderbilt / 28.09.2016 Interview with: Eric P Skaar, Ph.D., MPH Director, Division of Molecular Pathogenesis Ernest W. Goodpasture Professor of Pathology Vice Chair for Basic Research, Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine What is the background for this study? What are the main findings? Response: Nutrient metals are known to be a critical driver of the outcome of host-pathogen interactions, and C. difficile is the most common cause of hospital-acquired infections. C. difficile infection typically occurs following antibiotic-mediated disruption of the healthy microbiome. We were interested in learning how nutrient metals can shape the microbiome and impact the outcome of Clostridium difficile infection. We found that excess zinc alters the structure of the microbiome and increases the severity of C. difficile infection in mice. (more…)
Author Interviews, JCEM, Microbiome, Pediatrics, Weight Research, Yale / 21.09.2016 Interview with: Nicola Santoro, MD, PhD Associate Research Scientist in Pediatrics (Endocrinology) Yale University What is the background for this study? What are the main findings? Response: The study start from previous observations showing an association between the gut microbiota and obesity. Similarly to what previously described in adults and in children, we found an association between the gut microbiota and obesity. We took a step further and also observed that the gut flora is associated to body fat partitioning (amount of fat in the abdomen). Moreover, we observed that the effect of microbiota could be mediated by the short chain fatty acids a product of gut flora. (more…)
Author Interviews, Biomarkers, Heart Disease, Microbiome / 18.08.2016 Interview with: Lemin Zheng, Ph.D. Professor, Lab Director, and Principal Investigator The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine Peking University Health Science Center Beijing  China What is the background for this study? Response: Optical coherence tomography (OCT) has been considered as an ideal tool to characterize accurately atherosclerotic plaques and has potential to detect plaque rupture due to high-resolution (10-20 μm) cross-sectional images of tissue with near infrared light (1-3). Trimethylamine-N-oxide (TMAO) is a gut microbiota-dependent-generated metabolite which is associated with cardiovascular risk by a pathway involving dietary ingestion of nutrients containing trimethylamine, including phosphatidylcholine, choline, and L-carnitine (4-6). In the gut, choline, betaine and carnitine can be metabolized to trimethylamine (TMA) by gut flora microorganism. And TMA could be further oxidized to a proatherogenic species, TMAO, in the liver by flavin monooxygenases 3 (FMO3)4-6. These risk associations have been repeatedly shown in large observational trials (7-10). (more…)
Author Interviews, Microbiome, Pharmacology / 19.07.2016 Interview with: Mark Pimentel, MD Associate Professor, Medicine Director, GI Motility Program Director, GI Motility Laboratory Cedars-Sinai IBS-C Clinical Advisory Board (Chair) at Synthetic Biologics Los Angeles, CA What is the background for this study? Dr. Pimentel: The SYN-010 program is based on research from my group at Cedars-Sinai Medical Center, and other researchers and collaborators worldwide, investigating the role of intestinal methane production in functional gastrointestinal disorders. Low levels of intestinal methane are a ubiquitous by-product of normal intestinal microbial digestion; however, elevated intestinal methane levels are correlated with decreased intestinal motility and increased symptom severity in patients with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). Methane in humans is produced almost exclusively by the intestinal microorganism Methanobrevibacter smithii (M. smithii). Highest levels of M. smithii are found in the colon; however, overgrowth of M. smithii into the small intestine has also been observed. Previous work from my laboratory demonstrated that methane production by M. smithii in stool samples from IBS-C patients is inhibited by the lactone form of lovastatin. Lovastatin lactone does not appear to eradicate microbial species in the intestine, which should reduce the risk of intestinal dysbiosis and/or the development of microbial resistance. SYN-010 is a proprietary, modified-release, oral formulation of lovastatin lactone, designed to protect lovastatin lactone from the stomach and release the active ingredient in two different locations of the intestinal tract where the M. smithii reside. SYN-010 exerts its therapeutic effect at the level of the intestinal microbiome and does not require absorption into the systemic circulation or conversion of the active ingredient (lovastatin lactone) to the cholesterol lowering β-hydroxyacid form. (more…)
Author Interviews, Genetic Research, Microbiome, Rheumatology / 15.07.2016 Interview with: Veena Taneja, Ph.D Immunologist Mayo Clinic Rochester MN What is the background for this study? What are the main findings? Response: Gut bacteria have been suggested to be involved in pathogenesis of rheumatoid arthritis. We used new technology to sequence the bacteria in patients with rheumatoid arthritis and first degree relatives and healthy individuals. We found that patients had lower diversity of bacteria than healthy individuals and the composition of the gut microbiota differed between patients and healthy people. We could identify some bacteria that have expanded in patients though those are generally observed with low numbers in healthy individuals. We could define certain metabolic signatures that associated with microbial profile. For the first time, we could show a direct link between the arthritis-associated bacteria we identified and enhancement of arthritis using a mice carrying the RA-susceptible HLA gene. (more…)
Author Interviews, Infections, Microbiome, Pulmonary Disease / 06.07.2016 Interview with: Genevieve Marchand Ph.D., RMCCM SCCM(Env) Microbiologiste agréée & Biochimiste Chercheure, Prévention des risques chimiques et biologiques IRSST What is the background for this study? Response: It is well known that Health Care Workers (HCWs) are at risk of occupationally acquired infections. Some procedures, such as bronchoscopies, are recognized to be high-risk tasks. Most researches that have linked infectious risk to specific task in healthcare settings did not measure the real bioaerosol exposure. Those link where mostly made from epidemiology observations. The aim of this study was to qualify and quantify the real bioaerosol concentrations found during bronchoscopy procedures in order to estimate the true occupational risk. (more…)
Author Interviews, Microbiome, Multiple Sclerosis, Nutrition, Science / 02.07.2016 Interview with: Ashutosh K Mangalam PhD Assistant Professor Department of Pathology University of Iowa Iowa City, IA What is the background for this study? What are the main findings? Response: Every human carries trillions of bacteria in their gut (gut microbiome) and recent advances in research indicate that these tiny passengers play an important role in our overall health maintenance. Having evolved over the time span of millions of years with the gut microbiome, they keep us healthy in multiple ways such as fermentation and absorption of undigested carbohydrates, synthesis of some vitamins, metabolism of bile acids etc. However, new research suggests that gut microbiome, also regulating our body’s defense system. It is hypothesized that a diverse gut microbiome is good for our health and perturbations in this might predispose us to disease development. Therefore, we asked whether multiple sclerosis (MS) patients have a gut microbiome which is distinct from healthy individuals. We collected fecal samples from MS patients and healthy controls and performed microbiome analysis. I have recently moved to UI but the entire study was completed at Mayo Clinic Rochester. This study involved a big team comprised of neurologist, gastroenterologist, bioinformatician, system biologist and study coordinators. We found that  multiple sclerosis patients indeed have a gut microbiome which is different from what is observed in healthy people. We identified certain bacteria which are increased or decreased in the gut of patients with multiple sclerosis compared to healthy controls. (more…)
Author Interviews, Breast Cancer, Microbiome / 26.06.2016 Interview with: Gregor Reid, B.Sc. Hons., Ph.D., MBA, ARM, CCM, Dr. HS, FCAHS Director, Canadian Centre for Human Microbiome and Probiotic Research Lawson Health Research Institute London, Ontario, Canada What is the background for this study? What are the main findings? Response: Women who breast feed have reduced risk of breast cancer. Human milk has bacteria passed on to the child. These bacteria reach the breast through the nipple and from the gut via the blood. Lactobacilli and Bifidobacteria, beneficial bacteria, grow well in milk. So, I wondered what if women never lactate or breast feed, could bacteria be there? Could bacteria be in the tissue itself and influence whether you got or did not get cancer. Proving there are bacteria in the actual breast tissue itself was an interesting discovery defying previous beliefs. (more…)
Author Interviews, Microbiome, Transplantation / 23.06.2016 Interview with: Maria-Luisa Alegre, MD, PhD Professor of medicine University of Chicago What is the background for this study? What are the main findings? Response: Most of the research that investigates why/how transplanted organs are rejected has focused on the genetic disparities between the donor and the recipient. Foreign proteins in the donor organ are recognized by the immune system of the host, which becomes activated to reject the transplanted organ. This is why transplant recipients need to take immunosuppressive medications for the rest of their lives. Whether environmental factors, in addition to genetic factors, can also affect how the immune system is activated by the transplanted organ is much less understood. In particular, the microbiota, the communities of microbes that live on and in our body, is distinct in each individual and is known to affect the function of the immune system in diseases ranging from autoimmunity to cancer. Using mouse models of skin and heart transplantation, we investigated if the microbiota was an environmental factor that could affect the speed at which the immune system rejects a transplanted organ. We found that the microbial communities that colonize the donor and the host fine-tune the function of the immune system and control the strength with which the immune system reacts to a transplanted organ. (more…)
Author Interviews, Brigham & Women's - Harvard, Microbiome, Nature / 21.06.2016 Interview with: Amir Bashan, PhD, and Yang-Yu Liu, PhD Channing Division of Network Medicine Brigham and Women’s Hospital and Harvard Medical School Boston, Massachusetts What is the background for this study? What are the main findings? Response:  We coexist with a vast number of microbes—our microbiota—that live in and on our bodies, and play important roles in human physiology and diseases. Our microbiota is inherently dynamic and changes throughout our lives. The changeability of our microbiota offers opportunities for microbiome-based therapies, e.g. fecal microbiota transplantation (FMT) and probiotic administration, to restore or maintain our healthy microbiota. Yet, our microbiota is also highly personalized and possess unique microbial “fingerprints” in both species assemblages and abundance profiles. This raises fundamental concerns regarding the efficacy and long-term safety of generic microbiome-based therapies. In particular, it is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (i.e. universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. In this case, we have to design truly personalized interventions, which need to consider not only the unique microbial state of an individual but also the unique dynamics of the underlying microbial ecosystem. In addition, host-specific microbial dynamics, if they exist, raise a major safety concern for FMT, because although the healthy microbiota are stable in the donor’s gut, they may be shifted to an undesired state in the recipient’s gut. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. We can design general interventions to control the microbial state (in terms of species assemblage and abundance profile) of different individuals. (more…)
Author Interviews, JAMA, Microbiome, Pediatrics, Weight Research / 13.06.2016 Interview with: Dr. Katri Korpela, PhD University of Helsinki Helsinki What is the background for this study? What are the main findings? Dr. Korpela: Previous studies have shown that breastfeeding reduces the frequency of infections in the child and is associated with lower risk of childhood overweight. Conversely, antibiotic use in early life is associated with increased BMI. Both antibiotic use and breastfeeding are known to influence the infant's microbiota. However, these two factors have not been studied together and it was not known whether antibiotic use could modify the beneficial effects of breastfeeding. We collected data on lifetime antibiotic use, breastfeeding duration, and BMI in a group of daycare-attending children aged 2-6 years. We found that the beneficial effects on long breastfeeding, particularly as regards BMI development, were evident only in the children who did not get antibiotics in early life. Antibiotic use before or soon after weaning seemed to eliminate the protection against elevated BMI in preschool age and weaken the protection against infections after weaning. (more…)
Author Interviews, Cleveland Clinic, Heart Disease, Microbiome / 02.06.2016 Interview with: Dr. W.H. Wilson Tang M.D. Department of Cellular and Molecular Medicine (NC10) Cleveland Clinic Lerner Research Institute Cleveland, Ohio 44195 What is the background for this study? What are the main findings? Response: Our group has recently described the mechanistic link between intestinal microbe-generated phosphatidylcholine metabolite, trimethylamine N-oxide (TMAO), and the pathogenesis of atherosclerotic coronary artery disease (CAD) and its adverse clinical outcomes. Here in a separate, independent, contemporary cohort of patients undergoing coronary angiography, we demonstrated the association between elevated fasting TMAO levels and quantitative atherosclerotic burden (as measured by SYNTAX and SYNTAX II scores) in stable cardiac patients and is an independent predictor for the presence of diffuse (but not focal) lesion characteristics. (more…)
Author Interviews, Gastrointestinal Disease, Gluten, Microbiome / 02.06.2016 Interview with: Ettje Tigchelaar MSc PhD student from department of Genetics University of Groningen, Groningen What is the background for this study? What are the main findings? Response: A gluten-free diet is used by celiac disease patients to alleviate their symptoms. Previous research in these patients has shown differences in gut microbiota composition when on habitual gluten containing diet (HD) compared to a gluten-free diet (GFD). Recently more and more individuals without celiac disease also started to adopt a gluten-free diet to improve their health and/or control weight. We studied changes in gut microbiota composition in these healthy individuals on a gluten-free diet. We observed changes in the abundance of specific bacteria, for example the abundance of the bacterium family Veillonellaceae was much lower on a gluten-free diet versus HD, whereas it was higher for the family Clostridiaceae. We also looked at the function of the bacteria in the gut and found that many of those bacteria that changed because of the gluten-free diet played a role in metabolism of starch. This makes sense since starch is like gluten highly present in wheat containing products, thus when eliminating gluten from the diet, the intake of starch also changes and the gut bacteria processing this dietary starch change accordingly. (more…)
Author Interviews, Gastrointestinal Disease, Infections, Microbiome / 28.05.2016 Interview with: Jennifer Mahony, PhD and  Prof Douwe Van Sinderen Dept of Microbiology University College Cork Cork, Ireland Editor's note: Dr Jennifer Mahony & Prof Douwe van Sinderen, of the APC (Alimentary Pharmbiotic Center) Microbiome Institute, University College Cork, Ireland, have received a Grand Challenges Explorations Grant from the Bill & Melinda Gates Foundation to study the microbiota (bacteria and viruses) of infants in developing countries. This study seeks to improve the gut health of infants which could potentially prevent/reduce the estimated 0.8 million infants who die annually in developing countries. Dr. Mahony & Prof. van Sinderen answered several questions about the upcoming study for the audience. What is the background for this study? Would you briefly explain what is meant by a microbiome? Response: The World Health Organisation promotes exclusive breast-feeding in infants until they are at least 6 months old. Early weaning in developing countries where sanitary conditions may be poor may lead to the introduction of microorganisms such as Shigella, which can cause intestinal infections and in extreme cases may be fatal. 0.8 million infant deaths in developing countries could be avoided annually according to UNICEF if exclusive breast-feeding is continued to the sixth month of life. Our intestinal tracts naturally contain many bacteria, called our microbiota, and the composition of this microbiota may have implications for our health and well-being. Just in the same way that drinking a probiotic drink every day is reported to promote a healthy gut microbiota, we will investigate how bacterial viruses (that specifically infect bacteria and not humans!) can change the gut bacterial population. (more…)
Author Interviews, Microbiome, Neurological Disorders / 22.05.2016 Interview with: Susanne Asu Wolf PhD Max-Delbrueck-Center for Molecular Medicine Berlin, Germany What inspired you to research this link between Ly6Chi monocytes, antibiotics and neurogenesis? Dr. Wolf: As a neuroimmunologist I research the communication between the immune system and the brain. Amongst other research groups we found almost 10 years ago that T cells are needed to maintain brain homeostasis and plasticity, namely neurogenesis. Since only activated T cells enter the brain, we were looking for a mouse model, where immune cells are not activated. My former supervisor Polly Matzinger (NIH), a well-known immunologist, suggested to use germ free mice, born and raised in an isolator without any contact to a pathogen or any bacteria. I did a pilot experiment with the germ free mice, but wanted to get closer to possible applications in humans. Since humans are rarely born and raised in a sterile environment, I was looking for another model. By chance I met with the group of Bereswill and Heimesaat (Berlin, Charite) who provided me with a model, where due to prolonged treatment with an antibiotic cocktail, the microbiota are below detection level and the mice are also virtually germ free. They got me into contact with the second senior author of the paper Ildiko Dunay (University of Magdeburg). Her expertise is the function of Ly6Chi monocytes during infection with malaria or toxoplasmosis. Now we were ready to investigate the gut-immune-brain axis with the focus on neurogenesis and cognition. Meanwhile the impact of the microbiome on behavior was reported by several research groups using “sterile” germ free mice and I was also curious if we could see similar differences in our antibiotic treated mice. (more…)
Author Interviews, Microbiome / 19.05.2016 Interview with: Martha Colin Founder of The BioCollectiveMartha Carlin Founder of The BioCollective Editor’s Note: In recognition of the National Microbiome Initiative (NMI) announced by the White House Office of Science and Technology Policy, Martha Carlin, founder of the The BioCollective, discussed this research effort for the readers of ‘The BioCollective, is a direct-to-consumer microbiome marketplace where members receive a percentage of revenue from microbiome sample sales to scientists. By becoming a member of The BioCollective, individuals help advance microbiome research and learn about their own microbiome along the way.’ Would you tell us a little about yourself? How did you become interested in microbiomes? Martha Carlin: My husband was diagnosed with Parkinson’s Disease (PD) in 2002. At the time, John was 44 years old, a marathon runner and life-long athlete. He had always been healthy. We were both perplexed by both his diagnosis and wanted to do everything we could to maintain his quality of life as well as hinder the progression of the disease. Although I did not have a scientific background, I began studying the many fields of science so that I could piece together my observations of his health and his life history in my search for answers. After reading Dr. Martin Blaser’s Missing Microbes in 2014, I later connected it to Dr. Filip Scheperjans’ research showing a correlation between the presence or absence of specific gut bacteria and symptoms in Parkinson’s Disease. This accelerated my research and led me to Dr. Jack Gilbert at the University of Chicago who later became one of my co-founders. I started working with Jack on sequencing samples and learning more about the field of microbiome research. From this work, we saw a need for samples to accelerate the research and founded The BioCollective with our third co-founder, Dr. Suzanne Vernon. Can you briefly explain what a microbiome is? Does it just refer to the organisms in our intestines or are there other microbiomes? Are microbiomes unique to an individual or a community? Martha Carlin: The microbiome is the sum total of microbial life in your body - the bacteria, archaea, fungi and viruses that call you home. There are 100 trillion microbial cells in your body, and they collectively can influence your health in profound ways. The possibilities in microbiome research are exciting. It has the potential to create technologies as revolutionary as probiotics to prevent obesity and allergies; “living” buildings that reduce the spread of viruses or allergens in schools and offices; personalized diets to treat depression; growth-promoting animal feed that eliminates the need for growth-promoting antibiotics; bacteria to reduce methane production in cows and flooded soils; plant-microbiome interactions that suppress disease and improve productivity, and bacterial cocktails that restore the health of damaged aquatic ecosystems ranging from streams to oceans. (more…)
Author Interviews, Gastrointestinal Disease, Microbiome, Transplantation / 16.05.2016 Interview with: Dr. Sudarshan Paramsothy University of New South Wales Australia What is the background for this study? What are the main findings? Dr. Paramsothy: This study was conducted as there is strong evidence that the gastrointestinal microbiota play a critical role in the underlying pathogenesis of inflammatory bowel disease (IBD), but treatments to date primarily are focused on controlling the associated immune response. Attempts at therapeutic microbial manipulation in ulcerative colitis (UC) to date (antibiotics, probiotics, prebiotics) have not been as impressive as one might expect. We felt intensive fecal microbiota transplantation (FMT) may be more successful than these other methods, as it involves transplanting the entire gastrointestinal microbiota from a health individual, and thus more likely to correct any underlying microbial disturbance or dysbiosis in the recipient UC patient. Our study found that significantly more active ulcerative colitis patients treated with intensive FMT than placebo (27% vs 8%) achieved the trial primary composite endpoint of both
  • clinical remission induction (ie resolution of symptoms) and
  • endoscopic remission or response (ie either healing or significant improvement of the bowel lining)
Author Interviews, Gastrointestinal Disease, Microbiome, Nature, Technology / 12.05.2016 Interview with: Prof. Dr. Paul Wilmes Associate Professor Head of the Eco-Systems Biology Research Group Luxembourg Centre for Systems Biomedicine University of Luxembourg Luxembourg What is the background for this intestinal model? Dr. Wilmes: Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential. Widely used animal models exhibit limitations. Therefore, we set out to develop the HuMiX model which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal interface. (more…)
Author Interviews, Bipolar Disorder, Infections, Johns Hopkins, Mental Health Research, Microbiome, Schizophrenia / 05.05.2016 Interview with: Emily G. Severance, Ph.D Stanley Division of Developmental Neurovirology Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, MD What is the background for this study? What are the main findings? Dr. Severance: This research stems in part from anecdotal dialogues that we had with people with psychiatric disorders and their families, and repeatedly the issue of yeast infections came up. We found that Candida overgrowth was more prevalent in people with mental illness compared to those without psychiatric disorders and the patterns that we observed occurred in a surprisingly sex-specific manner.  The levels of IgG antibodies directed against the Candida albicans were elevated in males with schizophrenia and bipolar disorder compared to controls. In females, there were no differences in antibody levels between these groups, but in women with mental illness who had high amounts of these antibodies, we found significant memory deficits compared to those without evidence of past infection. (more…)
Author Interviews, Microbiome, Nutrition, Pediatrics, Weight Research / 05.05.2016 Interview with: Jacob (Jed) E. Friedman, Professor, Ph.D. Department of Pediatrics, Biochemistry & Molecular Genetics Director, NIH Center for Human Nutrition Research Metabolism Core Laboratory University of Colorado Anschutz What is the background for this study? What are the main findings? Response: Scientists have long established that children who are breastfed are less likely to be obese as adults, though they have yet to identify precisely how breastfeeding protects children against obesity. One likely reason is that children who are breastfed have different bacteria in their intestines than those who are formula fed. The study, published Monday in the American Journal of Clinical Nutrition examines the role of human milk hormones in the development of infants’ microbiome, a bacterial ecosystem in the digestive system that contributes to multiple facets of health. “This is the first study of its kind to suggest that hormones in human milk may play an important role in shaping a healthy infant microbiome,” said Bridget Young, co-first author and assistant professor of pediatric nutrition at CU Anschutz. “We’ve known for a long time that breast milk contributes to infant intestinal maturation and healthy growth. This study suggests that hormones in milk may be partly responsible for this positive impact through interactions with the infant’s developing microbiome.” Researchers found that levels of insulin and leptin in the breastmilk were positively associated with greater microbial diversity and families of bacteria in the infants’ stool. Insulin and leptin were associated with bacterial functions that help the intestine develop as a barrier against harmful toxins, which help prevent intestinal inflammation. By promoting a stronger intestinal barrier early in life, these hormones also may protect children from chronic low-grade inflammation, which can lead to a host of additional digestive problems and diseases. In addition, researchers found significant differences in the intestinal microbiome of breastfed infants who are born to mothers with obesity compared to those born to mothers of normal weight. Infants born to mothers with obesity showed a significant reduction in gammaproteobacteria, a pioneer species that aids in normal intestinal development and microbiome maturation. Gammaproteobacteria have been shown in mice and newborn infants to cause a healthy amount inflammation in their intestines, protecting them from inflammatory and autoimmune disorders later in life. The 2-week-old infants born to obese mothers in this study had a reduced number of gammaproteobacteria in the infant gut microbiome. (more…)