Author Interviews, C. difficile, Gastrointestinal Disease, Microbiome, Transplantation / 14.03.2017
Frozen Fecal Transplant in Pill Form Found To Reverse C. Diff Infection
MedicalResearch.com Interview with:
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Dr. DuPont[/caption]
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
MedicalResearch.com: 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.
Dr. DuPont[/caption]
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
MedicalResearch.com: 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.













Dr. Maria Luisa Alegre[/caption]
Maria-Luisa Alegre, MD, PhD
Professor of medicine
University of Chicago
MedicalResearch.com: 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.
Ettje Tigchelaar[/caption]
Ettje Tigchelaar MSc
PhD student from department of Genetics
University of Groningen, Groningen
MedicalResearch.com: 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.
Jennifer Mahony, PhD and Prof Douwe Van Sinderen[/caption]
Jennifer Mahony, PhD and
Prof Douwe Van Sinderen
Dept of Microbiology
University College Cork
Cork, Ireland
MedicalResearch.com 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 MedicalResearch.com audience.
MedicalResearch.com: 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.
Dr. Susanne Asu Wolf[/caption]
Susanne Asu Wolf PhD
Max-Delbrueck-Center for Molecular Medicine
Berlin, Germany
MedicalResearch.com: 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.
Martha Carlin
Founder of The BioCollective
MedicalResearch.com 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 MedicalResearch.com.
‘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.’
MedicalResearch.com: 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.
MedicalResearch.com: 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.
Paul Wilmes[/caption]
Prof. Dr. Paul Wilmes
Associate Professor
Head of the Eco-Systems Biology Research Group
Luxembourg Centre for Systems Biomedicine
University of Luxembourg
Luxembourg
MedicalResearch.com: 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.
Dr. Jed Friedman[/caption]
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
MedicalResearch.com: 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.





