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

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Prof. Elinav

Prof. Eran Elinav
Department of Immunology

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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.

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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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