Intestinal Microbiome Alterations May Trigger Immune Reactions Inducing Multiple Sclerosis

MedicalResearch.com Interview with:

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

Dr. Kouichi Ito

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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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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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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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.

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Gut and Brain Communicate To Drive Irritable Bowel Syndrome

MedicalResearch.com Interview with:

Laureate Professor Nicholas J. Talley, MBBS (Hons.)(NSW), MD (NSW), PhD (Syd), MMedSci (Clin Epi)(Newc.), FRACP, FAFPHM, FAHMS, FRCP (Lond. & Edin.), FACP, FACG, AGAF, FAMS, FRCPI (Hon), GAICD Pro Vice-Chancellor, Global Research, University of Newcastle, Australia Professor of Medicine, Faculty of Health and Medicine, University of Newcastle, Australia

Prof. Nicholas Talley

Laureate Professor Nicholas J. Talley, MBBS (Hons.)(NSW), MD (NSW), PhD (Syd), MMedSci (Clin Epi)(Newc.), FRACP, FAFPHM, FAHMS, FRCP (Lond. & Edin.), FACP, FACG, AGAF, FAMS, FRCPI (Hon), GAICD
Pro Vice-Chancellor, Global Research,
University of Newcastle, Australia
Professor of Medicine, Faculty of Health and Medicine, University of Newcastle, Australia
President, Royal Australasian College of Physicians
Chair, Committee of Presidents of Medical Colleges
Hon. Treasurer, Australian Academy of Health and Medical Sciences
Editor-in-Chief, Medical Journal of Australia
Senior Staff Specialist, John Hunter Hospital, Newcastle, Australia
Professor of Medicine and Professor of Epidemiology, Joint Supplemental Consultant Gastroenterology and Health Sciences Research, Mayo Clinic, Rochester, MN, USA

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

Response: Functional gastrointestinal diseases (FGIDs) like the irritable bowl syndrome (IBS) are very common, cause major distress including pain and psychological dysfunction, impact on quality of life and drive high health care costs. We speculated that there are two distinct types of functional gastrointestinal disease that others have not recognized.

For example, IBS in a subgroup may first begin with gut symptoms (pain, diarrhea, constipation, bloating etc) in those free of psychological distress and only later does new onset anxiety or depression develop, implicating gut disease as the primary driver of the entire symptom complex (a gut-to-brain disease). On the other hand, we speculated there is another quite different subgroup where disease begins with anxiety or depression and only later do new onset gut symptoms develop, and this is likely primarily a central nervous system cause (probably through the stress system), or a brain-to-gut disease. This is exactly what we found, with gut disease occurring first followed by new onset psychological distress in about two thirds of people from the community over a one year follow-up.

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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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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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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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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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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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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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Intestinal Bacterial Play a Role in Inflammation After Stroke

MedicalResearch.com Interview with:

Josef Anrather, VMD Finbar and Marianne Kenny Research Scholar Associate Professor, Feil Family Brain and Mind Research Institute Weill Cornell Medical College New York, NY10065

Dr. Josef Anrather

Josef Anrather, VMD
Finbar and Marianne Kenny Research Scholar
Associate Professor, Feil Family Brain and Mind Research Institute
Weill Cornell Medical College
New York, NY10065

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

Dr. Anrather: Worldwide, stroke is causing 5.6 million deaths annually. This ranks stroke as the second most common cause of death. Moreover, stroke is a leading cause of long-term disability. Stroke, even though primarily a vascular disease, has a strong inflammatory component both in rodent models and in clinics. While it is widely accepted that commensal bacteria shape the gastrointestinal immune system and have a strong impact on gastrointestinal immune diseases including Inflammatory Bowel Disease, Chron’s Disease and colitis, only recently it became evident that intestinal bacteria, at least in animal models, could alter disease course of a variety of autoimmune diseases including rheumatoid arthritis, diabetes, and multiple sclerosis. This was the point when our laboratory became interested in exploring the impact of intestinal bacteria on stroke. Although stroke is not an autoimmune disease and a role of the adaptive immune system during the acute phase of stroke is unlikely, we hypothesized that lymphoid cells more closely associated with the innate immune system, such as γδ T cells, might be also a target for intestinal bacteria.

Our study establishes a link between intestinal commensal bacteria and stroke outcome. Additionally, we show that immune cells in the gut matter and that the composition of intestinal immune cells has an impact on the immune response to stroke. One of the components identified by our study are γδ T cells which are regulated by the intestinal flora.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Anrather: The major message of our study is that stroke cannot be seen entirely as a isolated disease of the brain. There are components outside the brain that can influence the course and outcome of stroke. In our study we have identified the intestinal flora as a regulator of immune cells that participate in stroke. These immune cells are regulated in the gut through interaction with the commensal microbiota and can traffic to the meninges where they orchestrate the inflammatory response after stroke.

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

Dr. Anrather: Although the intestinal flora in humans seems relatively homogeneous among individuals at the phyla level, there is high inter-individual variation at lower taxonomic levels and only one third of bacterial genes are shared among individuals. This raises the question whether association with specific bacterial families or species could determine disease risk.

Future work will have to focus on establishing large population-level databases of enterotypes of the human gut microbiome, so we can use these epidemiological data to ask the question whether a certain microbial makeup is correlated with the frequency of cardiovascular events and – in the end – with stroke outcome. Once such microbial traits are identified there is the possibility of dietary or probiotic intervention to establish a flora with beneficial effect on the cardiovascular system.

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

Citation:

Corinne Benakis, David Brea, Silvia Caballero, Giuseppe Faraco, Jamie Moore, Michelle Murphy, Giulia Sita, Gianfranco Racchumi, Lilan Ling, Eric G Pamer, Costantino Iadecola, Josef Anrather.
Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cellsNature Medicine, 2016; DOI: 10.1038/nm.4068

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

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Emollient Treatment Improves Skin Microbiome in Atopic Dermatitis

MedicalResearch.com Interview with:

Sophie Seite, PhD La-Roche-Possy Dermatological Laboratories Asnières, France

Dr. Sophie Seite

Sophie Seite, PhD
La-Roche-Posay Dermatological Laboratories
Asnières, France

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

Dr. Seite: These studies were performed in order to confirm the previous results published by H. Kong et al showing that the skin microbiota of atopic dermatitis patients was less diversified and presented an overabundance of S. aureus in comparison to healthy subjects. Because each of us has a specific skin microbiota (huge inter-individual variation) we performed an intra-individual design protocol in order to compare the microbiome of a lesional skin area to those of a non-lesional adjacent area. This strategy showed that the skin diversity in AD patients was reduced in non-lesional area and even more in lesional area and that not only Staphylococcus aureus is overabundant but also Staphylococcus epidermidis and Staphylococcus haemolyticus. Furthermore, for the first time the effect of a topical treatment on the skin microbiome was evaluated. Prebiotic strategies using thermal spring water or biomass lysate of nonpathogenic bacteria demonstrated their efficiency for a long term management of AD patients through an action on the skin microbiome.

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Vaginal Seeding After C-Section Can Transfer Harmful Germs To Baby

MedicalResearch.com Interview with:

Dr. Aubrey Cunnington Faculty of Medicine, Department of Medicine Clinical Senior Lecturer Imperial College, London

Dr. Aubrey Cunnington

Dr. Aubrey Cunnington
Faculty of Medicine, Department of Medicine
Clinical Senior Lecturer
Imperial College, London

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

Dr. Cunnington: We noticed that increasing numbers of women who were having Caesarean section deliveries at our hospitals were requesting for their vaginal fluid to be swabbed onto their babies after birth – a process often termed “vaginal seeding”. The idea behind this, is that it transfers all the natural bacteria (microbiota) from the mother’s vagina to the baby. We know that early on in life, babies born by Caesarean section have different bacteria living on their bodies and in their guts to those of babies born by vaginal delivery. Some people think these differences in the microbiota may be responsible for differences in long-term health, although a causal link is unproven. The hope is that vaginal seeding might reduce the risk of the baby developing some diseases like obesity and asthma in the future. Unfortunately we are a long way from having the evidence to show that this is possible, and we do not know whether vaginal seeding is really safe. Babies born by elective Caesarean section are at lower risk of transfer of some potentially harmful bacteria and viruses from the birth canal, but these harmful bacteria and viruses could be transferred to the baby on a swab and potentially cause a devastating infection.

MedicalResearch.com Editor’s note:  ‘Vaginal Seeding’ is also known as “microbirthing”,   

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Babies’ Intestinal Microbiome Affected By Family Diet

MedicalResearch.com Interview with

Tine Rask Licht, Professor Head of Research Group on Gut Microbiology and Immunology Technical University of Denmark National Food Institute Søborg

Prof. Tine Rask Licht

Tine Rask Licht, Professor
Head of Research Group on Gut Microbiology and Immunology
Technical University of Denmark
National Food Institute Søborg

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

Response:  During childhood, the intestinal microbiota is under establishment. This period thus represents a ’window’, where the microbiota is likely to be more susceptible to be affected by external factors such as diet. Currently, it is well known that breast feeding has a major impact on the microbiota of young infants, but only very few studies have addressed the effect of the ‘next step’ in diet exposure, represented by complementary feeding.

We studied two cohorts of children, born to normal-weight and obese mothers, respectively, and mapped the composition of bacteria in their fecal microbiota at age 9 months and 18 months.  We found that at 9 months, the microbiota was clearly affected by the composition of the complementary diet, but not by maternal obesity.

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Microbiome Can Be Partially Restored in C-Section Delivered Babies

MedicalResearch.com Interview with:

Maria Dominguez-Bello, PhD Associate Professor, Department of Medicine, Division of Translational Medicine NYU Langone Medical Center

Dr. Dominguez-Bello

Maria Dominguez-Bello, PhD
Associate Professor, Department of Medicine, Division of Translational Medicine
NYU Langone Medical Center and

Jose Clemente, PhD Assistant Professor, Departments of Genetics and Genomic Sciences, and Medicine Icahn School of Medicine at Mount Sinai

Dr. Jose Clemente

Jose Clemente, PhD
Assistant Professor, Departments of Genetics and Genomic Sciences, and Medicine
Icahn School of Medicine at Mount Sinai    

 


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

Response: Humans and animals are a composite of their own cells and microbes.

But where they get their microbes from?  For mammals, labor and birth are major exposures to maternal vaginal bacteria, and infants are born already with a microbiota acquired from the mother.

Mom’s birth canal is heavily colonized by bacteria that are highly related to milk: some will use milk components and become dominant during early development, an important window for maturation of the immune system, the intestine and the brain. Thus, the maternal vaginal microbiota is thought to be of high adaptive value for newborn mammals. Indeed, studies in mice confirm that microbes acquired at birth are important to develop adequate immune and metabolic responses, and the mature adult microbiome will continue to modulate host metabolism and immunity.

Humans are the only mammals that interrupt the exposure to maternal vaginal microbiota, by delivering babies by Cesarean section. C-sections save lives of babies and moms, and they are estimated necessary in 10-15% of the cases. But most Western countries have rates above 30%, with the notable exception of the Scandinavian countries, Holland and Japan, which have excellent health systems and low maternal-infant mortality rates.

Previous work by us an others has shown that infants born by C-section acquire different microbiota at birth, and those differences are sustained over time, altering the normal age-dependent maturation of the microbiome. The fundamental questions are then, can we restore the microbiota of Cesarean delivered babies? And if we can, does that reduce the associated disease risks? In relation to the first question, we present here the results of a pilot study in which infants born by Cesarean delivery were exposed to maternal vaginal fluids at birth.

A total of 18 infants were recruited for the study. Seven of them were vaginally delivered, the remaining 11 were born by scheduled C-section. Among the C-section infants, 4 were exposed to maternal vaginal fluids at birth and 7 were not. We sampled all infants and their mothers for the first month of life across different body sites (oral, skin, anal, maternal vagina) and determined the microbiome composition on a total of over 1,500 samples.

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Babies’ Microbiome Affected by Cesarean Section and Formula Feeding

MedicalResearch.com Interview with:
Annie Gatewood Hoen, PhD 
Assistant Professor of Epidemiology and of Biomedical Data Science and
Juliette Madan, MD, MS
Associate Professor of Pediatrics
The Geisel School of Medicine at Dartmouth
Dartmouth-Hitchcock Medical Center
Lebanon, NH 03756

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

Response: When newborns are delivered they begin the process of acquiring vast numbers of bacteria that are critical for healthy nutrition and for immune training for a lifetime of health. Diseases such as obesity, heart disease, colitis, autism, and even cancer risk is associated with particular patterns in the gut microbiota; interestingly breast milk exposure is associated with decreased risk of many of these diseases. The intestinal microbiome plays a critical role in development, and delivery mode (cesarean section versus vaginal delivery) and feeding method (breast milk vs. formula) are important determinants of microbiome patterns.  We observed the intestinal microbiome in 6 week old infants and how it relates to delivery type and feeding. We were particularly interested in examining patterns in the microbiome in infants who received combination feeding of both breast milk and formula, an area that has been understudied.

We prospectively studied 102 infants and, with gene sequencing of bacteria, identified important patterns in microbiome composition that differed greatly based upon delivery method and between feeding groups.  Babies who were combination fed (formula and breast milk) had an intestinal microbiome that was more similar to babies who were exclusively formula fed than breast fed babies. We identified individual bacteria that were differentially abundant between delivery mode and feeding groups.

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Antibiotic Induced Depletion of Bile Acids Facilitates Growth of C. diff

Casey M. Theriot, Ph.D. Assistant Professor Infectious Disease College of Veterinary Medicine Department of Population Health and Pathobiology North Carolina State University Raleigh, NC 27607

Dr. Casey Theriot

MedicalResearch.com Interview with:
Casey M. Theriot, Ph.D.
Assistant Professor Infectious Disease
College of Veterinary Medicine
Department of Population Health and Pathobiology
North Carolina State University
Raleigh, NC 27607

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

Dr. Theriot: This study is an extension of the work we did in 2014 in our Nature Communications paper (Theriot et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, 2014). We really wanted to know how different antibiotics that varied in their mechanism of action altered the gut microbiota in different ways and also in turn how this altered the bile acids present in the small and large intestine of mice. Primary bile acids are made by the host and are further converted to secondary bile acids by members of the microbiota in the large intestine. We know from previous work that secondary bile acids can inhibit the growth of C. difficile, but no one has looked in depth at the bile acid makeup in the actual gut before in the context of C. difficile. In this study we show that specific antibiotics that significantly alter the large intestinal gut microbiota and deplete all secondary bile acids allow for C. difficile to grow without any inhibition. We also showed that C. difficile spores are always germinating in the small intestine, which means in order to prevent this pathogen from colonizing the gut, we will have to target the growth of the pathogen. Moving forward the focus will be on trying to repopulate the gut with bacteria that are capable of restoring the secondary bile acid pools in order to inhibit C. difficile.

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Intestinal Pathogens Change the Microbiome, Cause E. Coli To “Bloom”

Shannon D. Manning, Ph.D., M.P.H. Dept. of Microbiology and Molecular Genetics Michigan State University E. Lansing, MI 48824

Dr. Manning

MedicalResearch.com Interview with:
Shannon D. Manning, Ph.D., M.P.H
.
Dept. of Microbiology and Molecular Genetics
Michigan State University
E. Lansing, MI 48824

Medical Research: What is the background for this study? What are the main findings?
Dr. Manning: Diarrheal disease is a leading cause of morbidity and mortality in children under the age of five and is commonly caused by many different bacterial pathogens.

We have observed that infection with four different bacterial pathogens (Salmonella, Shigella, Shiga toxin-producing E. coli, and Campylobacter) all induce the proliferation of a population of microbes, namely Escherichia, which are already present in the gut of healthy individuals.

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Evelo Therapeutics Seeks To Disrupt Cancer Enabling Effects of Microbiome

MedicalResearch.com Interview with:
Simba Gill Ph.D

CEO, Evelo Therapeutics

MedicalResearch: Evelo Therapeutics, a new company focuses on leveraging the power of the microbiome to develop novel therapies for cancer. Evelo is pioneering Oncobiotic™ therapeutics, a new modality in cancer therapy based on the cancer microbiome.
Dr. Gill, CEO of  Evelo Therapeutics began his career at Celltech, focused on antibody research. Dr. Gill earned his Ph.D. from King’s College, London, and his MBA from INSEAD.

Medical Research:  What is a microbiome? How do microbiomes play a role in health and disease?

Dr. Gill: The microbiome is the collection of trillions of bacteria, funguses, viruses and other microbes that live on and within the human body. There are different clusters of microbes in different parts of the body, including the skin, mouth, large intestine, and vagina.

Recently we have learned that our microbial populations shift depending on changes to an individual’s health and wellness. The makeup of one’s microbiome has a strong influence on one’s health, immune response, and metabolic state.

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Microbiome Signature Can Predict Risk of C. difficile Treatment Failure

Dr. Sahil Khanna MBBS Assistant Professor of Medicine Mayo Clinic

Dr. Sahil Khanna

MedicalResearch.com Interview with:
Dr. Sahil Khanna MBBS
Assistant Professor of Medicine
Mayo Clinic

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

Response: C. difficile infection patients are at a high risk of complications such as treatment failure. Gut microbiota signatures associated with CDI have been described but it is unclear if differences in gut microbiota play a role in response to therapy. No studies have identified predictors of treatment failure and we aimed to identified gut microbiota signatures to predict response to treatment for primary C. difficile . While there were no clinical predictors of treatment response, there were increases in certain genera in patients with successful treatment response in the fecal samples at initial diagnosis compared to non-responders. A risk index built from this panel of microbes highly differentiated between patients based on response and ROC curve analysis showed that this risk index was a strong predictor of treatment response, with a high area under the curve of 0.83..

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Intestinal Bacteria May Play A Role in Anorexia Nervosa

Dr. Ian Carroll, PhD Professor of medicine UNC Center for Gastrointestinal Biology and DiseaseMedicalResearch.com Interview with:
Dr. Ian Carroll, PhD
Professor of medicine
UNC Center for Gastrointestinal Biology and Disease 

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

Dr. Carroll: Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme weight dysregulation and presents with high rates of comorbid anxiety.Anorexia nervosa carries the highest mortality rate of all psychiatric illnesses and relapse is frequent. Although a prime contributor, genetic factors do not fully account for the etiology ofAnorexia nervosa, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from Anorexia nervosa. Our study provides evidence of an intestinal dysbiosis in AN and an association between mood and the enteric microbiota in this patient population.

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Diets Rich in Vegetables May Reduce Heart Disease Risk Through Microbiome Changes

Prof. Danilo Ercolini, PhD Department of Agricultural Sciences University of Naples Federico II Portici - ItalyMedicalResearch.com Interview with:
Prof. Danilo Ercolini, PhD
Department of Agricultural Sciences
University of Naples Federico II
Portici – Italy

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

Prof. Ercolini: There is a thick body of literature showing that diet can significantly impact the gut microbiota and metabolome.

In a recent study, negligible differences in gut microbiota and feca lshort-chain fatty acids (SCFA) were reported between habitual omnivores and vegans in the USA.

In addition, Mediterranean diet is a recognized healthy dietary pattern but has not previously been related to the composition of the gut microbiota and related metabolome. That’s the background in short.

Here we show how habitual vegetarian and vegan diets promote enrichment of fibre-degrading bacteria in the gut.

Subjects who consume a Mediterranean diet rich in fruit, legumes and vegetables have higher levels of fecal short chain fatty acids, regardless of the diet type.

Low adherence to the Mediterranean diet corresponds to an increase in urinary trimethylamine oxide levels, a potential risk factor for cardiovascular disease.

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