PCOS: Hyperandrogenism Associated With Changes in Gut Microbiome

MedicalResearch.com Interview with:

Varykina Thackray, Ph.D. Associate Professor of Reproductive Medicine University of California, San Diego

Dr. Thackray

Varykina Thackray, Ph.D.
Associate Professor of Reproductive Medicine
University of California, San Diego

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

Response: Previous studies have shown that changes in the composition of intestinal microbes (gut microbiome) are associated with metabolic diseases. Since many women with polycystic ovary syndrome (PCOS) have metabolic dysregulation that increases the risk of developing type 2 diabetes and cardiovascular disease, we wondered whether PCOS was associated with changes in the gut microbiome and if these changes were linked to any clinical features of PCOS.

We collaborated with Beata Banaszewska and her colleagues at the Poznan University of Medical Sciences in Poznan, Poland to obtain clinical data and fecal samples from 163 premenopausal women recruited for the study. In collaboration with Scott Kelley at San Diego State University, we used 16S ribosomal RNA gene sequencing and bioinformatics analyses to show that the diversity of the gut microbiome was reduced in Polish women with PCOS compared to healthy women and women with polycystic ovaries but no other symptoms of PCOS.

The study confirmed findings reported in two other recent studies with smaller cohorts of Caucasian and Han Chinese women. Since many factors could affect the gut microbiome in women with PCOS, regression analysis was used to identify clinical hallmarks that correlated with changes in the gut microbiome. In contrast to body mass index or insulin resistance, hyperandrogenism was associated with changes in the gut microbiome in this cohort of women, suggesting that elevated testosterone may be an important factor in shaping the gut microbiome in women.

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C-Section and Formula-Fed Babies Have Different Microbiome From Breastfed or Vaginal Births

MedicalResearch.com Interview with:

Anita Kozyrskyj, PhD, Professor Dept Pediatrics Faculty of Medicine & Dentistry, University of Alberta Edmonton, AB   

Dr. Kozyrskyj

Anita Kozyrskyj, PhD, Professor
Dept Pediatrics
Faculty of Medicine & Dentistry, University of Alberta
Edmonton, AB   

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

Response: The first year of an infant’s life is a critical time for the development of his or her gut microbiome. Gut microbes not only help infants digest food, but they also “train” their developing immune system. An infant’s environment, from the type of birth and infant diet to use of antibiotics, has a large impact in determining which microbes are present. Frequently these early life exposures occur together. Using data from AllerGen’s CHILD birth cohort and a new analytical approach —called Significance Analysis of Microarrays—we quantified changes to gut microbiota throughout the first year of life according to common combinations of early life exposures.

We found that, compared to vaginally-born and breastfed infants, formula-fed or cesarean-delivered infants had different trajectories of microbial colonization in later infancy, which could have implications for their future health.

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Intestinal Microbiome Linked To Pediatric Asthma

MedicalResearch.com Interview with:

Anita Kozyrskyj, PhD, Professor, Dept Pediatrics Faculty of Medicine & Dentistry, University of Alberta Edmonton, AB 

Dr. Kozyrskyj

Anita Kozyrskyj, PhD, Professor, Dept Pediatrics
Faculty of Medicine & Dentistry, University of Alberta
Edmonton, AB  

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

Response: I was motivated to study the maternal asthma-infant microbiome link by the well-established fact that maternal asthma affects infant birth weight in a sex-specific manner. Based on data from AllerGen’s CHILD birth cohort, Caucasian baby boys born to pregnant moms with asthma—putting them at the highest risk for developing asthma in early childhood—were one-third as likely to have high levels of the microbe, Lactobacillus, in their gut microbiome at 3-4 months after birth.

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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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