Intestinal Microbiome Alterations May Trigger Immune Reactions Inducing Multiple Sclerosis

MedicalResearch.com Interview with:

multiple sclerosis on mri Wikipedia Image James Heilman, MD

Multiple sclerosis as see on MRI

Kouichi Ito, PhD
Associate Professor
Department of Neurology
Robert Wood Johnson Medical School
Rutgers

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), and breakdown of immune tolerance to CNS proteins has been suggested to initiate CNS autoimmunity. Although the mechanism underlying the breakdown of immune tolerance to CNS proteins is still unknown, gut microbiota has been suggested to be involved in disease initiation and progression.

To investigate the etiology of Multiple Sclerosis, we have created humanized transgenic mice expressing MHC class II and T cell receptor genes isolated from an Multiple Sclerosis patient and showed that gut dysbiosis, alteration in intestinal microbial composition, can induce gut leakiness and subsequently trigger the development of neurological deficits through activation of complement C3 and reduction of CBLB and Foxp3 genes.

This study suggests that gut dysbiosis is one of the possible etiological factors for Multiple Sclerosis.

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Prebiotin™ Fiber Supplement Tested in NIH/NIDDK Pilot Study In End-Stage Kidney Disease Patients

MedicalResearch.com Interview with:

Ron Walborn Jr. Prebiotin CEO

Ron Walborn Jr.

Ron Walborn Jr.
Prebiotin CEO 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The product Prebiotin™ Prebiotic Fiber was brought to market in 2007 by Dr. Frank Jackson, a gastroenterologist out of Harrisburg, PA. He found through 40 years of experience with his patients that a variety of digestive issues benefitted from daily supplementation with a soluble prebiotic fiber, specifically, oligofructose-enriched inulin (OEI) derived from chicory root.

In the late summer of 2012, Prebiotin caught the attention of Dr. Dominic Raj at the Internal Medicine Department of George Washington University. Dr. Raj’s laboratory showed that patients with kidney disease may have a higher level of release of endotoxins like p-Cresol sulfate and indole from the bacteria in the gut, which can move into the bloodstream and promote inflammation.

This early work was the basis of a successful grant application. Researchers were interested in investigating the therapeutic potential of altering the composition and/or function of the gut microbiome in this patient population, based on the understanding that by building up the levels of healthy bacteria in the gut, undesirable bacteria is eventually crowded out, thereby reducing the release of harmful endotoxins into the system.

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Gut Microbiome of Health Very Old Similar To Younger Adults

MedicalResearch.com Interview with:
Greg Gloor, PhD
Principal investigator
Professor at Western’s Schulich School of Medicine & Dentistry and
Scientist at Lawson Health Research Institute.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We sampled the bacteria in the gut (stool) in over 1000 members of a super healthy population in China across the age ranges of 3 to over 100. Exclusion criteria included a history of genetic or chronic disease (intergenerational in the case of people younger than 30), no smoking, drinking or drug use (including no prescription drugs).

Our goal was to identify what, if any changes in the makeup of the gut microbiota occurred in this population so that we could define “what is associated with health”.

We found three things.

  • First, that the expected differences between the very young and everyone else were found in this population. This indicates that we could observe the standards signatures of a maturing gut microbiota.
  • Second, that the gut microbiota of very healthy very elderly group (over 95 yo) was very similar to that of any very healthy person over the age of 30.
  • Third, we found that the gut microbiota of 20yo people (in three distinct groups) was different from all other age groups. The reason for the differences observed in the 20 yo groups from all the others is unknown, but is not methodological in origin.

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Organic Compounds In Bowel Responsible For Longer Healthier Lives in Variety of Species

MedicalResearch.com Interview with:

Daniel Kalman, Ph.D. Department of Pathology and Laboratory Medicine Emory University

Dr. Kalman

Daniel Kalman, Ph.D.
Department of Pathology and Laboratory Medicine
Emory University

MedicalResearch.com: What is the background for this study? What are the main findings?

  1. We think a lot about living longer, but that means we will also have a longer period of frailty and infirmity, which isn’t optimal. Moreover, with geriatric populations projected to expand by 350 fold over the next 40 years, healthcare costs will be unsustainable.
  2. We were interested in understanding how health span of animals is regulated, and whether the microbiota plays a role. The microbiota, which is composed of bacteria inside and on us, when dysregulated (called dysbiosis) contributes to disease; the question we asked was whether it could also contribute to healthy aging, and how.
  3. We showed that animals of widely divergent phyla and separated by hundreds of millions of years of evolutionary time, all utilize indoles to regulate how well they age; in short indoles  make older animals look younger by various metrics, including motility, and fecundity.

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Risk of Inflammatory Bowel Disease Lower In Rural Households

MedicalResearch.com Interview with:

Eric I. Benchimol, MD, PhD, FRCPC Associate Professor of Pediatrics and Epidemiology, University of Ottawa Division of Gastroenterology, Hepatology and Nutrition Children's Hospital of Eastern Ontario Ottawa, ON Canada

Dr. Benchimol

Eric I. Benchimol, MD, PhD, FRCPC
Associate Professor of Pediatrics and Epidemiology, University of Ottawa
Division of Gastroenterology, Hepatology and Nutrition
Children’s Hospital of Eastern Ontario
Ottawa, ON Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We found that living in a rural household (compared to urban households) was protective against developing inflammatory bowel disease (IBD). People living in a rural household were around 10% less likely to get IBD (Crohn’s disease and ulcerative colitis).

While our finding that IBD was more common in people living in urban households was similar to other studies from around the world, there were a number of new, interesting findings:

  1. Living in a rural household was most protective against pediatric-onset IBD. In fact, it was not protective in IBD with onset between ages 18-39, 40-64, or 65 and older at diagnosis.
  2. Living in a rural household in the first 5 years of life was highly protective against IBD later in life.

These findings indicate the importance of early life environmental exposures in the subsequent development of IBD. This effect has been seen in the inflammatory bowel disease literature when examining other environmental risk factors, particularly early-life antibiotic use and air pollution. These risk factors seem to have the strongest effect of increasing the risk of childhood-onset IBD, and not adult-onset disease.

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Diabetes Alters Oral Microbiome Leading to Periodontal Disease

MedicalResearch.com Interview with:

Dana T. Graves DDS Department of Periodontics School of Dental Medicine University of Pennsylvania Philadelphia, PA

Dr. Graves

Dana T. Graves DDS
Department of Periodontics
School of Dental Medicine
University of Pennsylvania
Philadelphia, PA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It was previously thought that diabetes did not have a significant effect on oral bacteria. We found that diabetes caused a change in the composition of the oral bacteria. This change caused resulted in a bacterial composition that was more pathogenic and stimulated more inflammation in the gums and greater loss of bone around the teeth.

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What Type of Bread Is Best For Your Glycemic Index?

MedicalResearch.com Interview with:

Prof. Avraham A. Levy Department of Plant and Environmental Sciences Weizmann Institute of Science Rehovot Israel

Prof. Levy

Prof. Avraham A. Levy
Department of Plant and Environmental Sciences

Prof-Eran-Elinav.jpg

Prof. Elinav

Prof. Eran Elinav
Department of Immunology

Prof-Eran-Segal.jpg

Prof. Segal

Prof. Eran Segal
Department of Computer Science And Applied Math

Weizmann Institute of Science, Rehovot Israel

MedicalResearch.com: What is the background for this study? 

Response: We performed a type of clinical trial that is very powerful in comparing short term effects of interventions – a crossover trial. In this trial, each subject is compared to themselves; in our case, we compared increased short-term (1 week) consumption of industrial white bread vs. matched consumption of artisanal sourdough-leavened whole-wheat bread – which we originally viewed as radical opposites in terms of their health benefits. We measured various clinical end points – weight, blood pressure, various blood tests – and also the gut microbiome.

To our great surprise, we found no difference between the effects those two breads had on the various end points that we measured. This does not mean that bread consumption had no effect – but that this effect was generally similar for its two types. In fact, when we analyzed our data when pooling together the two bread types (i.e., testing whether bread of any type had an effect), we found that just one week of bread consumption resulted in statistically significant changes to multiple clinical parameters – on the one hand, we saw a reduction in essential minerals in the blood (calcium, magnesium, iron) and an increase in LDH (marker of tissue damage); on the other hand, we saw an improvement in markers of liver and kidney function, inflammation markers and cholesterol levels.

In terms of the microbiome, we have found only a minimal difference between the effects of the two bread (two microbial taxa that were increased with white bread) – but in general, we saw that the microbiome was very resilient to this intervention. This is surprising as the current paradigm in the field is that a change in nutrition rapidly changes the makeup of the microbiome. We say that this is probably dependent on the kind of change – as we had a nutritional change here which was significant enough to change clinical parameters, which we tend to think of as very stable, and yet had a minimal effect on the microbiome.

At this point, there were two possible explanations to what we saw:
The first is that bread had an effect in our intervention, but it was very similar between those two very distinct types.
The second is that these two distinct types indeed had different effects, but they were different for each subject – and thus cancel out when we look at the entire population.

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Microbiome Regulates Fear Response via the Amygdala

MedicalResearch.com Interview with:

Dr. Gerard Clarke PhD APC Microbiome Institute Department of Psychiatry and Neurobehavioural Science University College Cork, Cork, Ireland

Dr. Clarke

Dr. Gerard Clarke PhD
APC Microbiome Institute
Department of Psychiatry and Neurobehavioural Science
University College Cork, Cork, Ireland

MedicalResearch.com: What is the background for this study?

Response: Over the last decade or so, we and others have shown that the gut microbiome exerts a broad influence on the central nervous system, reflected in a range of abnormal behaviours and altered brain function in germ-free animals. These germ-free animals grow up in a sterile bubble and allow us to see what aspects of brain and behaviour could be under the influence of the microorganisms in our gastrointestinal tract.

One of the most consistent findings to emerge relates to anxiety-like behaviours.

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New Drug May Protect Gut From Antibiotic-Resistance Genes

MedicalResearch.com Interview with:

Synthetic Biologics, Inc.

Synthetic Biologics, Inc.

Sheila Connelly, PhD
Vice President, Research
Synthetic Biologics, Inc.

MedicalResearch.com: What is the background for this study?

Response: Synthetic Biologics, Inc. is focused on the protection and preservation of the gut microbiome which is the diverse collection of microorganisms that live in the intestinal tract. We are learning that the gut microbiome plays a key role in health. Negative changes to the microbiome, called dysbiosis, are linked to disease states including allergies, autism, and obesity, among a rapidly growing list of other conditions. A consequence of using antibiotics is that, in addition to fighting the bacterial infection being treated, they also kill the gut microbiota. The space left in the gut by the dead bacteria allows other surviving bacteria, many times opportunistic pathogens or microbes that are resistant to multiple antibiotics, to overgrow and fill the open niches. Exposure to antibiotics, particularly broad-spectrum antimicrobials, such as penicillins and cephalosporins, is a major risk factor for acquiring a potentially deadly Clostridium difficile infection.

Dr-Sheila-Connelly.jpg

Dr. Sheila Connelly

Another consequence of antibiotic use is the emergence of antibiotic-resistant organisms. Widespread use of antibiotics provides selective pressure for the evolution of lethal, multi-drug resistant pathogens, termed “nightmare bacteria”. The gut microbiome acts as a reservoir of antibiotic resistance that can be triggered, by antibiotic exposure, to acquire and propagate resistance genes.

A way to protect the microbiome and reduce antibiotic resistance is to limit exposure of the gut microbiota to antibiotics. To this end, we developed an antibiotic inactivation strategy using a beta-lactamase enzyme to degrade beta-lactam antibiotics in the GI tract before they can harm the gut microbiome. Beta-lactamases are naturally-occurring bacterial enzymes that confer resistance to beta-lactams, the most widely used broad spectrum antibiotics, and their presence is normally considered an obstacle to efficacious infection control. We took advantage of the highly efficient antibiotic degradation activity of a beta-lactamase and developed SYN-004 (ribaxamase). Ribaxamase is a beta-lactamase engineered to inactivate penicillins and most cephalosporins, formulated for oral delivery, and intended for use with IV beta-lactam antibiotics to degrade the antibiotics in the GI tract to protect the microbiome.

Ribaxamase was demonstrated to significantly reduce the occurrence of C. difficile disease in a recently completed Phase 2b clinical study. The study met its primary endpoint by demonstrating that ribaxamase, when delivered orally with IV ceftriaxone, significantly reduced C. difficile disease in patients treated for a respiratory tract infection. Ribaxamase also resulted in a significant reduction in new colonization by vancomycin-resistant enterococcus (VRE).

For the current study, pig models of antibiotic-mediated gut dysbiosis were established using three classes of beta-lactam antibiotics, a cephalosporin, ceftriaxone, a penicillin, amoxicillin, and a carbapenem, ertapenem. The ceftriaxone model was used to evaluate the protective effect of ribaxamase on the microbiome and the amoxicillin and ertapenem models are intended for evaluation of pipeline products.

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Diet Foods Can Make You Fat By Changing Your Microbiome

MedicalResearch.com Interview with:

Krzysztof Czaja VBDI, D.V.M Associate professor of veterinary biosciences and diagnostic imaging College of Veterinary Medicine University of Georgia

Dr. Krzysztof Czaja

Krzysztof Czaja VBDI, D.V.M
Associate professor of veterinary biosciences and diagnostic imaging
College of Veterinary Medicine
University of Georgia

MedicalResearch.com: What is the background for this study?

Response: The neural regulation of food intake and satiety in rodents and human are similar. Therefore, rodent model is well established in studying neural regulation in obesity in humans.

MedicalResearch.com: What are the main findings?

Response: We determined that diets rich in sugar, and many “diet products” contain high amount of sugar (sometimes under different names), increase efficiency of accumulation of body and liver fat. We also found that sugar-rich diets change the gut microflora toward overpopulation of enterotoxic bacteria, damaging neural gut-brain communication and disrupting neural regulation of food intake. The implications of our results on human health are very significant because they show that diets rich in sugar changes the brain circuits responsible for food intake and satiety, induces chronic inflammation and symptoms of non-alcoholic liver disease (NALD).

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Exposure To Furry Pets During Pregnancy and Babyhood May Help Keep Your Child Lean

MedicalResearch.com Interview with:

Anita Kozyrskyj, PhD Department of Pediatrics Faculty of Medicine & Dentistry University of Alberta

Dr. Anita Kozyrskyj

Anita Kozyrskyj, PhD
Department of Pediatrics
Faculty of Medicine & Dentistry
University of Alberta

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have known for a while that early-life exposure to household pets can reduce risk for allergic disease; new studies also suggest a benefit in preventing overweight. Our pilot study in 2013 showed that postnatal pet exposure increases the number of different beneficial microbes in the infant gut. My team of 12, including first author and Albert Innovates-Health Solutions (AIHS) postdoctoral fellow Hein Min Tun, took the science one step closer to understanding this connection in our recently published work in the Microbiome journal. In a study of 746 infants from the Canadian Healthy Infant Longitudinal Development Study (CHILD) birth cohort, we investigated the impact of pet exposure during pregnancy or afterwards on infant gut microbes, and whether this depended on how infants were born.

In infants born vaginally or by cesarean section, pet exposure during pregnancy or pre and postnatally up to 3 months after birth increased the amounts of 2 bacteria found on dogs and cats. One is Ruminococcus, linked to lower rates of allergies in children. The other is a relatively unknown microbe, Oscillospira, reported to promote leanness. Another important finding suggested that contact with pets during pregnancy could reduce transmission of vaginal GBS (group B Streptococcus) during birth.

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Athletes’ Microbiome May Be Conditioned For Performance

MedicalResearch.com Interview with:
Dr. Orla O’Sullivan

Computational Biologist,
Teagasc Food Research Centre,
Moorepark, Co. Cork,
Ireland 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previously we had demonstrated that professional rugby players had significantly increased microbial diversity compared to both low and high BMI controls. This microbial diversity correlated with creatine kinase levels in the blood (which we had used as a proxy for exercise) and protein intake. In this present study we went a step further and demonstrated that these same athletes had distinct functional potential in their gut microbes compared to controls and furthermore both the host derived ( urine) and bacterial derived ( faecal water) metabolites were also distinct in the athlete group. In particular we found that the athlete’s microbiome is primed for tissue repair and to harness energy from the diet, reflecting the significant energy demands and high cell-turnover evident in elite sport.

Thus, the state of physical fitness is not limited to the host alone; it appears to also include conditioning of the microbiota.

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Probiotics May Influence Schizophrenia Symptoms Through Yeast in Microbiome

MedicalResearch.com Interview with:
Emily G. Severance PhD
Stanley Division of Developmental Neurovirology
Department of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD 21287

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previously, we found that people with schizophrenia and bipolar disorder had an increased susceptibility to Candida albicans yeast infections, which was sex specific and associated with memory deficits. Also in an earlier placebo-controlled probiotic study, we found that although probiotics improved the overall bowel function of people with schizophrenia, there was no effect by this treatment on psychiatric symptoms.  Given that C. albicans infections can upset the dynamics of the human microbiome, we decided to re-evaluate the potential benefit of probiotics in the context of a patient’s C. albicans yeast status.  Not only was bowel function again enhanced following intake of probiotics, but yeast antibody levels were decreased by this treatment.

Furthermore, psychiatric symptoms were actually improved over time for men receiving probiotics who did not have elevated C. albicans antibodies. Men who were positive for C. albicans exposure, however, consistently presented with worse psychiatric symptoms irrespective of probiotic or placebo treatment.

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Antibiotics in Pregnancy Increase Children’s Risk of Otitis Media and Ventilation Tubes

MedicalResearch.com Interview with:
Hans Bisgaard, MD, DMSc

Professor of Pediatrics
The Faculty of Health Sciences
University of Copenhagen
Copenhagen University Hospital, Gentofte
Copenhagen, Denmark

MedicalResearch.com: What is the background for this study?

Response: The consumption of antibiotics is increasing worldwide. Antibiotics alter the maternal bacterial colonization and by vertical transmission this can affect the offspring. An unfavorable microbiome may increase the disease propensity of the offspring.
Otitis media is one of the most common infections in early childhood. We hypothesized that antibiotic consumption in pregnancy can increase the children’s risk of otitis media.
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Viral Bacterial Parasites Called Phages Drive Co-Evolution of Gut Microbiome

MedicalResearch.com Interview with:

Dr Pauline Scanlan Royal Society-Science Foundation Ireland University Research Fellow/APC Faculty, APC Microbiome Institute, Biosciences, University College Cork, Éire

Dr. Scanlan

Dr Pauline Scanlan
Royal Society-Science Foundation Ireland University Research Fellow/APC Faculty,
APC Microbiome Institute, Biosciences,
University College Cork, Éire

MedicalResearch.com: What is the background for this study?

Response: The human gut is host to an incredible diversity of microbes collectively known as the gut microbiome. Each of us has a unique collection of bacterial strains that form part of the gut microbiome. This uniqueness is of potentially crucial importance with respect to host health as we know that differences in bacterial strain diversity within species could have a range of positive or negative consequences for the human host. For example, some strains of a given bacteria are harmless whilst another strain of the same bacterial species could kill you. A classic example of such a difference in strain functionality is exemplified by the gut bacterium Escherichia coli – one strain called E. coli Nissle 1917 is used as a probiotic and another, E. coli O157:H7, has been responsible for a number of deadly food-borne pathogen outbreaks. Therefore a better understanding of what drives bacterial strain diversity is not just fundamental to our understanding of the ecology and evolution of microbes but is also highly relevant for improvements in human health and disease prevention.

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Protective Bacteria May Reverse Inflammation In Some Forms of IBD

MedicalResearch.com Interview with:
Justin E. Wilson, Ph.D 
On behalf of the authors
Research Assistant Professor – Laboratory of Jenny Ting
Department of Genetics
Lineberger Comprehensive Cancer Center
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599

MedicalResearch.com: Could you provide me with some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper?

Response: Previous work from our lab and others discovered two major points about NLRP12:
a) NLRP12 suppresses inflammation in response to bacterial components
b) NLRP12 provides protection against the inflammatory bowel disease colitis and colitis-associated colon cancer (i.e., Nlrp12-defcient mice have greater colon inflammation and inflammation-driven colon cancer).
Therefore, we wanted to know if Nlrp12 was regulating inflammation in the colon by responding to the trillions of intestinal microbes collective referred to as the microbiome. Mounting evidence also indicates that the immune system both responds to and influences the composition of the intestinal microbiome during intestinal health and disease, and we hypothesized that NLRP12 could be one of the important immune components during this process. Moreover, we were also interested in this topic because targeting the microbiome to treat inflammatory disorders and other diseases is an attractive method that has many advantages over immune suppression.

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Frozen Fecal Transplant in Pill Form Found To Reverse C. Diff Infection

MedicalResearch.com 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

Dr. DuPont

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.

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Cardioprotective Effect of Soy in Japanese May Be Mediated Through Equol

MedicalResearch.com Interview with:

Akira Sekikawa, Ph.D.</strong> Associate professor of epidemiology University of Pittsburgh Graduate School of Public Health

Dr. Sekikawa

Akira Sekikawa, Ph.D.
Associate professor of epidemiology
University of Pittsburgh Graduate School of Public Health

MedicalResearch.com: 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.

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Intestinal E. coli Linked to Arthritis in Inflammatory Bowel Disease

MedicalResearch.com 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

Dr. Randy Longman

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 

MedicalResearch.com: 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.

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Investigational Compound Improves Gut Microbiome Without Long-Term GI Symptoms

MedicalResearch.com Interview with:

Fernando Azpiroz, MD, PhD Chief of the Department of Digestive Diseases University Hospital Vall d’Hebron Autonomous University of Barcelona, Spain

Dr. Fernando Azpiroz

Fernando Azpiroz, MD, PhD
Chief of the Department of Digestive Diseases
University Hospital Vall d’Hebron
Autonomous University of Barcelona, Spain

MedicalResearch.com: 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).

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Intestinal and Blood-Brain Barrier Alterations Linked to Autism Spectrum Disorders

MedicalResearch.com Interview with:

Maria Rosaria Fiorentino, PhD

Dr. Maria Rosaria Fiorentino

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

MedicalResearch.com: 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.

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Gut Inflammation & Bacterial Changes Linked to Type 1 Diabetes

MedicalResearch.com 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

Prof Lorenzo Piemonti

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

MedicalResearch.com: 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.

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Uterine Microbiome Plays Key Role in IVF Success

MedicalResearch.com 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

Dr. Carlos Simón

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

MedicalResearch.com: 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.

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Microbiome Is Major Driver of Recurrent Obesity

MedicalResearch.com Interview with:
Dr. Eran Elinav. Principal investigator
Immunology Department
Weizmann Institute of Science
Rehovot, Israel

MedicalResearch.com: 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.

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Without Fiber, Gut Bacteria Begin To Eat Our Intestinal Lining

MedicalResearch.com Interview with:

Mahesh Desai, PhD Principal Investigator Allergology - Immunology - Inflammation Research Unit Department of Infection and Immunity Luxembourg Institute of Health Luxembourg

Dr. Mahesh Desai

MedicalResearch.com: 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.

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Excess Zinc May Predispose to C.diff By Altering Gut Microbiome

MedicalResearch.com 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

Dr. Eric P Skaar,

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

MedicalResearch.com: 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.

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Intestinal Microbiome Linked to Obesity and Fat Storage in Children

MedicalResearch.com Interview with:

Nicola Santoro, MD, PhD Associate Research Scientist in Pediatrics (Endocrinology) Yale University

Dr. Nicola Santoro

Nicola Santoro, MD, PhD
Associate Research Scientist in Pediatrics (Endocrinology)
Yale University

MedicalResearch.com: 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.

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Circulating TMAO Levels Correlate with Coronary Plaque Vulnerability and Rupture

MedicalResearch.com Interview with:

Lemin Zheng, Ph.D.

Dr. Lemin Zheng

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

MedicalResearch.com: 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).

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Abnormal Microbiome Found in Preterm Infants Who Develop Chronic Lung Disease

Charitharth ‘Vivek' Lal, MD Assistant Professor, Division of Neonatal-Perinatal Medicine, Departments of Pediatrics University of Alabama at Birmingham Birmingham, AL 35249-7335

Dr. Lal

MedicalResearch.com Interview with:
Charitharth ‘Vivek’ Lal, MD
Assistant Professor,
Division of Neonatal-Perinatal Medicine,
Departments of Pediatrics
University of Alabama at Birmingham
Birmingham, AL 35249-7335

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Airway microbiome of neonates, at birth, has not been studied. Also, association of airway microbiome with lung disease of prematurity has not been studied well.

We found that infant airway is already colonized with bacteria or bacterial DNA when a baby is born. The extremely low birth weight (ELBW) infants who went on to develop life-threatening bronchopulmonary dysplasia showed abnormal microbial colonization patterns at birth, as compared to pre-term infants who did not get BPD. These findings were validated from a second independent set of patients, from a different clinical site.

MedicalResearch.com: What should readers take away from your report?

Response: Early airway microbiome dysbiosis may be associated with subsequent lung diseases and presence of lactobacillus in the airway of preterm infants may be protective. In addition, the newborn may acquire the airway microbiome / bacterial DNA, transplacentally or from the amniotic fluid.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response:
• To study the effects of pulmonary microbiome in various lung disease processes.
• To study the mechanisms by which the respiratory microbiome affect host response.
• To study the gut – lung microbial axis.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

The Airway Microbiome at Birth
Charitharth Vivek Lal , Colm Travers, Zubair H. Aghai , Peter Eipers , Tamas Jilling , Brian Halloran,Waldemar A. Carlo, Jordan Keeley , Gabriel Rezonzew , Ranjit Kumar, Casey Morrow , Vineet Bhandari & Namasivayam Ambalavanan
Published online: 04 August 2016
Scientific Reports 6, Article number: 31023 (2016)
doi:10.1038/srep31023

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Phase 2 Trials of Methane Inhibitor Improved Symptoms of Irritable Bowel Syndrome

MedicalResearch.com Interview with:

Mark Pimentel, MD Associate Professor, Medicine Director, GI Motility Program Director, GI Motility Laboratory Cedars-Sinai

Dr. Mark Pimentel

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

MedicalResearch.com: 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.

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Gut Bacteria May Play Role in Rheumatoid Arthritis Activity

MedicalResearch.com Interview with:

Veena Taneja, Ph.D Immunologist Mayo Clinic Rochester MN

Dr. Veena Taneja

Veena Taneja, Ph.D
Immunologist
Mayo Clinic
Rochester MN

MedicalResearch.com: 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.

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Bronchoscopy Can Expose Health Care Workers To Pathogens in Aerosol

MedicalResearch.com Interview with:

Genevieve Marchand Ph.D., RMCCM SCCM(Env) Microbiologiste agréée & Biochimiste Chercheure, Prévention des risques chimiques et biologiques IRSST

Dr-Genevieve-Marchand

Genevieve Marchand Ph.D., RMCCM SCCM(Env)
Microbiologiste agréée & Biochimiste
Chercheure, Prévention des risques chimiques et biologiques
IRSST

MedicalResearch.com: 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.

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Multiple Sclerosis Patients Have Altered Microbiome That May Benefit From Dietary Changes

MedicalResearch.com Interview with:

Ashutosh K Mangalam PhD Assistant Professor Department of Pathology University of Iowa Iowa City, IA

Mangalam~Ashu

Ashutosh K Mangalam PhD
Assistant Professor
Department of Pathology
University of Iowa
Iowa City, IA

MedicalResearch.com: 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.

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Women With Breast Cancer Have Different Bacterial Microbiome in Breasts

MedicalResearch.com 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

Dr. Gregory Reid

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

MedicalResearch.com: 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.

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Microbiome Affects the Immune System of Transplanted Organs

MedicalResearch.com Interview with:

Maria-Luisa Alegre, MD, PhD Professor of medicine University of Chicago

Dr. Maria Luisa Alegre

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.

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Model Deepens Understanding of Human Microbiomes

MedicalResearch.com 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

MedicalResearch.com: 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.

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Antibiotics Weaken Protective Effect of Breastfeeding on Pediatric Infections and Obesity

MedicalResearch.com Interview with:

Dr. Katri Korpela, PhD University of Helsinki Helsinki

Dr. Katri Korpela

Dr. Katri Korpela, PhD
University of Helsinki
Helsinki

MedicalResearch.com: 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.

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Intestinal Metabolite Associated With Diffuse Atherosclerosis

MedicalResearch.com Interview with:

Dr. W.H. Wilson Tang M.D. Department of Cellular and Molecular Medicine (NC10) Cleveland Clinic Lerner Research Institute Cleveland, Ohio 44195

Dr. W.H.Wilson Tang

Dr. W.H. Wilson Tang M.D.
Department of Cellular and Molecular Medicine (NC10)
Cleveland Clinic Lerner Research Institute
Cleveland, Ohio 44195

MedicalResearch.com: 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.

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Gluten-Free Diet Induces Changes In Gut Microbiome

MedicalResearch.com Interview with:

Ettje Tigchelaar MSc PhD student from department of Genetics University of Groningen, Groningen

Ettje Tigchelaar

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.

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Bill & Melinda Gates Foundation To Support Study of Microbiome of Infants in Developing Countries

MedicalResearch.com Interview with:

Jennifer Mahony, PhD Prof Douwe Van Sinderen

Jennifer Mahony, PhD and Prof Douwe Van Sinderen

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.

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Prolonged Antibiotic Therapy May Impact Brain Function

MedicalResearch.com Interview with:

Susanne Asu Wolf PhD Max-Delbrueck-Center for Molecular Medicine Berlin, Germany

Dr. Susanne Asu Wolf

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.

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The BioCollective Brings Public Input Into Microbiome Research

MedicalResearch.com Interview with:
Martha Colin Founder of The BioCollectiveMartha 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.

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Fecal Microbiota Transplantation is Promising Option for Ulcerative Colitis Treatment

MedicalResearch.com Interview with:
Dr. Sudarshan Paramsothy

University of New South Wales
Australia

MedicalResearch.com: 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)

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HuMiX Effectively Models Human Intestinal Microbiome

MedicalResearch.com Interview with:

Paul Wilmes

Paul Wilmes

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.

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Candida Yeast Infections Linked to Schizophrenia and Bipolar Disorder

MedicalResearch.com Interview with:

Emily G. Severance, Ph.D Stanley Division of Developmental Neurovirology Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, MD

Dr. Emily Severance

Emily G. Severance, Ph.D
Stanley Division of Developmental Neurovirology
Department of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD 

MedicalResearch.com: 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.

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Hormones in Breast Milk Shape Infant’s Microbiome

MedicalResearch.com 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

Dr. Jed Friedman

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.

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Intestinal Bacteria May Decrease Cancer Risk By Reducing Inflammation

MedicalResearch.com Interview with:

Robert H. Schiestl PhD Department of Environmental Health Sciences, Fielding School of Public Health, Department of Pathology Department of Radiation Oncology Geffen School of Medicine University of California Los Angeles, Los Angeles, California

Dr. Robert Schiestl

Robert H. Schiestl PhD
Department of Environmental Health Sciences, Fielding School of Public Health,
Department of Pathology
Department of Radiation Oncology
Geffen School of Medicine
University of California Los Angeles,
Los Angeles, California

Medical Research: What is the background for this study? What are the main findings?

Dr. Schiestl: When we moved from Harvard to UCLA 13 years ago, after 6 years at UCLA our Atm mouse colony lived significantly 4 fold longer and the frequency of DNA deletions was 4.5 fold reduced and the latency of lymphoma 2.5 fold different. Ultimately we identified the reason behind this as a difference in the intestinal bacteria. The Atm deficient mice are hypersensitive to inflammation and the bacteria reduced inflammation. Then I isolated the most prevalent bacterium among the health beneficial bacteria and this bacterium by itself called Lactobacillus johnsonii 456 reduced genotoxicity and all markers of inflammation.

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Gut Microbiome May Play Role in Myelination Disorders Including Multiple Sclerosis

MedicalResearch.com Interview with:

Professor JF Cryan PhD Department of Anatomy and Neuroscience APC Microbiome Institute University College Cork Cork, Ireland

Prof. John Cryan

Professor JF Cryan PhD
Department of Anatomy and Neuroscience
APC Microbiome Institute
University College Cork
Cork, Ireland

MedicalResearch.com: What is the background for this study? What are the main findings? 

Prof. Cryan: Over the past decade there has been an ever growing body of preclinical studies that highlight an essential role of the gut microbiota in many aspects of physiology including and perhps most surprtisingly the brain . Germ-free animals are one useful approach used to establish causality in gut microbiota-brain relationships. This model has been extremely useful in establishing that the microbiota is essential for appropriate stress responsibility, anxiety-like behaviours, neurogenesis, blood-brain barrier function and microglia activity. From these findings we can see that there is a clear cut role for the microbiota in CNS developmental processes.

Here we wanted to investigate using next generation sequencing, as we had done previously in the amygdala what impact life without microbes has on transcriptional regulation in the prefrontal cortex, a brain region essential in many aspects of emotional behaviour. What we uncovered from this was that there was a large number of dysregulated genes in germ-free animals that have a direct role in myelination. We found increased expression levels of genes that encode for structural proteins that are key in forming the myelin sheath. We followed up this finding with transmission electron microscopy to identify whether this marked increase in myelin related gene expression was functional at a structural level. What we found was germ-free myelinated axons in the prefrontal cortex were hypermyelinated (lower g-ratio), they had thicker myelin sheaths compared to conventionally raised mice. Additionally we also had germ-free colonized animals, animals that were born germ-free but have been colonized with a conventional microbiome early in life. These animals displayed no change in myelin related gene expression and appeared to be indistinguishable from the conventional animals. However, at the protein levels they appeared to have increased myelin protein like germ-free mice. This could be due to the fact that these mice were germ-free for at least 3 weeks of life and the hypermyelinated axons had already been established before colonization. Really this shows that we can still target the microbiota in later life that can have an impact of myelin gene regulation.
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Quitting Smoking Can Restore Normal Bacteria To Oral Microbiome

MedicalResearch.com Interview with:
Jiyoung Ahn, PhD, RD, MS
Associate Professor of Population Health
Associate Director of Population Sciences,
NYU Perlmutter Cancer Center  and
Brandilyn Peters (post-doctoral fellow, lead author)
NYU Langone School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Oral bacteria play important roles in oral health, and can influence the health of other body systems as well. We were interested in studying how cigarette smoking affects oral bacteria. To do this, we examined the oral bacteria in mouthwash samples from 112 current smokers, 571 former smokers, and 521 people who never smoked. We found that the mouth bacterial composition of current smokers differed dramatically from those who never smoked. However, the mouth bacterial composition of former smokers was similar to that of never smokers, suggesting that quitting can restore the oral bacteria back to a healthy state.

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Immune System Uses Mucous To Anchor Desired Bacteria to Intestine

MedicalResearch.com Interview with:

Jonas Schluter, DPhil Memorial Sloan Kettering Cancer Center New York City

Dr. Jonas Schluter

Jonas Schluter, DPhil
Memorial Sloan Kettering Cancer Center
New York City

Kirstie McLoughlin Department of Zoology Oxford University

Dr. Kirstie McLoughlin

Kirstie McLoughlin
Department of Zoology
Oxford University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Microbes in our guts perform many important functions for our health. Healthy individuals are inhabited by a complex microbial community. A less diverse community is often a sign of ill health, and can be accompanied by loss of beneficial functions that a normal microbial community provides for the host.

We try to understand how such complex communities can persist – after all, competition between microbes could lead to the eradication of slow-growing, but helpful microbes. We built a computer model of the gut that allows us to simulate how the host can actively help such slow microbes, and thereby maintain a healthily diverse microbial community. We show that a mechanism by which the host can achieve such selection is via secretions that help slow growing microbes persist by sticking in place.

We propose that the host can change microbiota composition by conveying increased adhesion to disadvantages microbes, for example using mucus molecules and the attached sugars such as fucose. We hypothesise that this might also help explain the secretion of vast amounts of immune system molecules such as immunoglobulin A – perhaps they are not only a way to harm, but also to help certain microbes by anchoring them to the mucus. Indeed, we demonstrate that the host can change the selective effect of increased adhesion by tuning the mucus secretion rate: from beneficial for the adhered microbes at low mucus flow to detrimental at high mucus secretion rates.

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