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.
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.
Author Interviews, Diabetes, mBio, Microbiome / 04.06.2015

Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242MedicalResearch.com Interview with: Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242 Medical Research: What is the background for this study? Dr. Schlievert:
  1. As people become obese and enter pre-diabetes type II, there is a gut microbiome shift in bacteria from Bacteroidetes to Firmicutes. A dominant pathogenic Firmicute in humans is Staphylococcus aureus.
  2. As people become obese, their skin becomes wetter due to enhanced sweating upon exertion and the presence of more skin folds. These, plus mucous membranes have enhanced Staphylococcus aureus numbers, such that 100% of people become colonized and numbers of the bacterium rise to 1013 per person. This number of bacteria is like a cubic inch of margarine spread across the skin and mucous membranes.
  3. All pathogenic Staphylococcus aureus bacteria make and secrete a family of toxins called superantigens, including toxic shock syndrome toxin and staphylococcal enterotoxins. In high amounts (0.1 μg/human), these toxins can be lethal, causing toxic shock syndrome. At lower concentrations, the same superantigen toxins cause total body inflammation without lethality.
  4. In order to show that a microbes causes human disease, it is necessary to fulfill Koch’s postulates:
    1. Must associate human symptoms with a particular disease,
    2. Must isolate a potentially causative bacterium that is always present when the disease is present.
    3. Must produce the disease in an experimental animal.
    4. Must re-isolate the microbe from the experimental animal and re-cause the disease in another animal.
Medical Research: What are the main findings? Dr. Schlievert: We have fulfilled Koch’s postulates, showing that Staphylococcus aureus and its superantigen toxins cause type II diabetes.
Author Interviews, 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.
AACR, Author Interviews, Cancer Research, Dental Research, Microbiome / 20.04.2015

Xiaodan Mai MBBS University at Buffalo, The State University of New York Buffalo, NYMedicalResearch.com Interview with: Xiaodan Mai MBBS University at Buffalo, The State University of New York Buffalo, NY MedicalResearch: What is the background for this study? What are the main findings? Response: Periodontal disease is a condition that is highly prevalent amongst the elderly, and is characterized by chronic polymicrobial infection and inflammation of gum tissue. Periodontal disease has been associated with increased cancer risk, and these findings may be partially explained by extra-oral translocation of subgingival bacteria that subsequently modulates host cell environment and function. However, there is limited research on whether the presence of certain subgingival bacteria influences cancer risk. . Oral bacteria have been categorized into color-coded complexes by their timing of colonization and strength of association with periodontal disease. Using data from an ancillary study of the Women’s Health Initiative conducted in Buffalo, New York (a cohort of 1300 postmenopausal women), we therefore investigated the associations between the presence of three early-colonizing periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus, i.e., "orange complex" bacteria moderately associated with PD), the presence of two late-colonizing periodontal pathogens (Porphyromonas gingivalis, Tannerella forsythia, i.e., "red complex" bacteria strongly associated with PD) in dental plaque and cancer risk. We found borderline associations between presence of any early-colonizing pathogens and increased risk of total cancer and lung cancer. Individual pathogens were not associated with total cancer or site-specific cancers when analyzed singly. Presence of any pathogens or presence of any late-colonizing pathogens was not associated with total or site-specific cancer.
Author Interviews, Microbiome, Pediatrics, Weight Research / 10.04.2015

MedicalResearch.com Interview with: Lisa J. Martin PhD Professor Division of Human Genetics Jessica G. Woo PhD Associate Professor Division of Biostatistics and Epidemiology Cincinnati Children’s Hospital Medical Center Cincinnati, OH MedicalResearch: What is the background for this study? Response: Obesity is a major public health concern. In the past 30 years, more and more children are being considered obese. Because treatment is challenging, researchers are looking toward prevention. The health benefits of breastfeeding over infant formula feeding are well recognized, including evidence that breastfeeding may protect against obesity. But, how much protection it provides and the reasons for protection are unclear. Thus, the purpose of this paper was to examine the relationship between breastfeeding and reduced risk of obesity later in life, with special emphasis on potential mechanisms. MedicalResearch: What are the main findings? Response: After reviewing more than 80 studies conducted over a period of 20 years, the authors showed that breastfeeding is associated with a 10 to 20 percent reduction in obesity prevalence in childhood. Mechanisms that connect human milk and infant physiology include maternal obesity, development of a healthy gut environment (microbiome) in the infant, and the development of taste preference and diet quality. Importantly, each of these mechanisms can be influenced by biologic and social factors which may directly and indirectly affect the child’s obesity risk.
Author Interviews, C. difficile, Gastrointestinal Disease, Microbiome / 01.04.2015

Michael J Sadowsky Ph.D Director, BioTechnology Institute University of MinnesotaMedicalResearch.com Interview with: Michael J Sadowsky Ph.D Director, BioTechnology Institute University of Minnesota MedicalResearch: What is the background for this study? What are the main findings? Dr. Sadowsky: Fecal microbiota transplantation (FMT) has become increasingly common in the treatment of patients with refractory Clostridium difficile infection (CDI). It also holds promise for the treatment of medical conditions ranging from inflammatory bowel and Crohn’s disease to diabetes and metabolic syndrome. In contrast to standard antibiotic therapies, which further disrupt intestinal microflora and may contribute to the recurrence of CDI, FMT restores intestinal microbiome and healthy gut function. Despite therapeutic successes, little is known about the stability of transplanted microbiota over time. This report contributes to our understanding of the short-and long-term composition of gut microbiota following Fecal microbiota transplantation. In this study, fecal samples collected before and after treatment were compared with data from the Human Microbiome Project (HMP). Treatment using FMT resulted in the rapid normalization of microbial composition in the patient, with the post-treatment profiles closely resembling the normal distribution of fecal microbiota from the donor. While the composition of fecal microbiota in the donor and recipient varied over time, both remained in the large band characterized as normal in hundreds of healthy individuals collected as part of the HMP. Furthermore, while the composition of the microflora in Fecal microbiota transplantation recipients and donors diverges over time, the recipient profiles stay within the same dynamic range as the original implanted donor material.
Author Interviews, Infections, Microbiome, Urology / 01.04.2015

Alan J. Wolfe PhD, Professor Department of Microbiology and Immunology Stritch School of Medicine, Loyola University Chicago Maywood, ILMedicalResearch.com Interview with: Alan J. Wolfe PhD, Professor Department of Microbiology and Immunology Stritch School of Medicine, Loyola University Chicago Maywood, IL

Medical Research: What is the background for this study? Dr. Wolfe: Several years ago, Dr. Brubaker and I began a conversation. As a urogynecologist, she was concerned about the general lack of improvement in diagnosis and treatment in her urogynecological practice and thus in clinical outcome. As a microbiologist, I was extremely skeptical of the dogma that urine in the bladder was sterile in the absence of a clinical infection. This skepticism was based upon my former work in bacterial motility and biofilm formation and on the knowledge that most bacteria are not cultured by the standard clinical microbiology urine culture method. With the goal of ultimately improving urogynecological practice, and with the help of our colleagues in the Loyola Urinary Education and Research Collaborative (LUEREC), we decided to test the sterile bladder hypothesis by seeking evidence of bacteria in urine taken directly from the bladder to avoid vulva-vaginal contamination. To detect bacterial DNA, we used high-throughput DNA sequencing technology. To detect live bacteria, we developed an Expanded Quantitative Urine Culture (EQUC) protocol. We applied these complementary approaches to women with and without urgency urinary incontinence (UUI) whose standard clinical urine culture was negative. Medical Research: What are the main findings? Dr. Wolfe: First and foremost, the bladder is not sterile. We can detect bacteria and/or bacterial DNA in most women whether they have urgency urinary incontinence (UUI) or not. Thus, the female bladder contains a resident bacterial community, which we call the female urinary microbiome (FUM). We found that bacterial members of the FUM are distinct from the bacteria that typically cause urinary tract infections (UTI). Thus, the bacteria that make up the FUM are not the bacteria that cause typical UTIs. Indeed, detection of the female urinary microbiome was associated with reduced risk of UTIs that often occur after instrumentation or surgery. We therefore hypothesize that the FUM or some members of the FUM could protect against UTI. We also saw that the FUM in women with UUI differs from the FUM in women without UUI and that certain bacterial species were considerably more common in women with urgency urinary incontinence than in women without urgency urinary incontinence . We hypothesize that some of these bacteria could be causative or contributory to UUI or they could be a consequence of urgency urinary incontinence.
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, Author Interviews, Microbiome, Pediatrics / 04.03.2015

Anita Kozyrskyj Ph.D Professor, Department of Pediatrics University of AlbertaMedicalResearch.com Interview with: Anita Kozyrskyj Ph.D Professor, Department of Pediatrics University of Alberta Medical Research: What is the background for this study? What are the main findings? Prof. Kozyrskyj: Our study determined what "good" gut bacteria were present in 166 full-term infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Funded by CIHR and AllerGen NCE, this landmark study involves more than 3,500 families and their newborn infants across Canada. Gut bacteria were identified by DNA sequences extracted from infant poop. Infants with a fewer number of different bacteria in their gut at 3 months of age were more likely to become sensitized to foods such as milk, egg or peanut, by the time they were 1 years old. Infants who developed food sensitization also had altered levels of two specific types of bacteria, Enterobacteriaceae and Bacteroidaceae, compared to infants who didn’t.
Allergies, Author Interviews, Microbiome, Pediatrics / 24.02.2015

Dr. Bill Hesselmar University of Gothenburg SwedenMedicalResearch.com Interview with: Dr. Bill Hesselmar University of Gothenburg Sweden MedicalResearch: What is the background for this study? What are the main findings? Dr. Hesselmar: The hygiene hypothesis is the background for this study, and the hypothesis states that children’s immune system need to be stimulated by bacteria and microbes to mature in a proper way prevent the children from developing immune mediated diseases such as allergies. There are increasing support for the hygiene hypothesis, with less allergies found in children from milieus with a rich microbial exposure such as: growing up on a farm or in a developing country, in children with many siblings, and after vaginal delivery as compared to caesarean section. Even though these findings are interesting from a theoretical point of view, they can’t be use in primary prevention since you can’t recommend anyone to live by a farm. We are investigating if there are harmless “microbial sources” in different daily life-situations that are good enough to stimulate children’s immune system. So far we have observed two such possible sources, the sharing of children’s pacifier (Pediatrics 2013) and hand dishwashing (this study). These are, however, only observational data – we have only found an association between hand dishwashing and a lower risk of allergy, we don’t know for sure that the lower risk of allergy was just because of the hand dishwashing. So far we regard it as an “interesting observation”, which need to be confirmed in new studies before any general conclusions could be made. The main findings was a lower risk of allergy (Odds Ratio 0,57) in children from hand dishwashing families as compared to children from families who use machine dishwashing.       
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.