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Landmark study reveals first genetic snapshots of unique placental microbiome
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2014-05-29 14:23:18 UTC
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Landmark study reveals first genetic snapshots of unique placental microbiome


Dr. Kjersti Aagaard, associate professor of obstetrics and gynecology in the section of maternal fetal medicine at Baylor and the Texas Children's Pavilion for Women.
The placenta is not as sterile as once thought. New research shows that the placenta harbors a unique, low abundant microbiome, said researchers from Baylor College of Medicine and Texas Children's Hospital.

The findings, in the current issue of the journal Science Translational Medicine, provide important new insights on the structure of the placental microbial community, the organisms present, and how they might be capable of impacting a pregnancy.

"After we completed our studies of the vaginal microbiome in pregnancy, we noted that the most abundant microbes in the mom's vagina were not what populated the baby's intestinal microbiome," said Dr. Kjersti Aagaard, associate professor of obstetrics and gynecology in the section of maternal fetal medicine at Baylor and the Texas Children's Pavilion for Women, and the lead and corresponding author on the report. "We reasoned that there must be another source 'seeding' the infant's gut at birth, so we sought to examine the placenta."

The microbiome is the population of microbes - bacteria, viruses and fungi - that cohabit with human cells and help cells complete their tasks. Understanding what characterizes the microbiome communities is essential for understanding human development, Aagaard said.

Aagaard and her colleagues are key members in the collaborative National Institutes of Health funded Human Microbiome Project, which seeks to further characterize these communities and how they relate to health and healing human disease.

In this study, the first and largest study to focus on the placental microbiome, 320 human subjects' samples were analyzed comprehensively following a process called shotgun metagenomic sequencing. This technology enables microbiologists to uniquely evaluate bacterial diversity and detect the abundance of specific microbes and all their genetic pathways in a community.

Implications for oral health

The researchers showed that the placenta is not sterile (free from bacteria or other living organisms), but rather harbors a diverse and very unique microbiome.

"The placental microbiome is low in terms of microbial abundance but not as sterile as we previously thought," said Aagaard.

Of the samples, Escherichia coli (E. coli) was the species with the highest abundance in most individuals, a bacteria that lives in the intestines of most healthy individuals. Prevotella tannerae (gingival crevices) and non-pathogenic Neisseria species (mucosal special surfaces), both species of the oral cavity, were also detected in highest relative abundance.

"Interestingly, when we looked very thoroughly at the placenta in relation to many other sites of the body, we found that the placental microbiome does not bear many similarities to microbiomes closest in terms of anatomic location. Specifically, it is not much like the vaginal or intestinal microbiome, but rather is most similar to the oral microbiome," said Aagaard.

The finding has important implications on the likely importance of oral health during pregnancy, she said. "It reinforces long-standing data relating periodontal disease to risk of preterm birth."

Microbiome and preterm birth

Additionally, the researchers observed differences in the placental microbiome based on a remote history of infection during the pregnancy (most commonly urinary tract infections from many months ago that were treated successfully with antibiotics).

The placental microbiome is also unique based on whether a preterm birth occurred, the researchers found.

"Exposure of the fetus to a placental microbiome may have fundamental implications for early human development and the physiology of pregnancy," said Dr. James Versalovic, co-author on the report, professor of pathology at Baylor and head of pathology at Texas Children's Hospital.

A larger study is currently underway to expand these findings to describe the placental and microbiome profiles across pregnancy and in relation with preterm birth.

"The hope is that we will get a clearer picture of how several of the microbial communities in women and their placentas change over the course of the entire pregnancy among those at risk for preterm birth. These discoveries could lead to rapid breakthroughs in not only identifying women at risk for preterm birth, but developing new and worthwhile strategies to prevent preterm birth," said Aagaard. "As we catch glimmers of the microbial biology of pregnancy, we can start to see a not too distant future where we will prevent preterm birth (or its complications in newborns) with truly novel approaches aimed at enhancing the healthy microbes of not just the vagina, but the mouth and gut. As we unravel the mysteries of pregnancy, we are learning that our microbes may be as much friend as foe. That is fantastic news for our moms and their babies."

Additional authors include Jun Ma, Dr. Kathleen M. Antony, Dr. Radhika Ganu and Dr. Joseph Petrosino all of Baylor.

Funding for this work was provided by the National Institutes of Health Director's New Innovator Award (to Aagaard); the Burroughs Welcome Fund Preterm Birth Initiative (to Aagaard and Versalovic); the National Institutes of Health's National Human Genome Research Institute as well as the Director's Common Fund (to Aagaard, Versalovic, and Petrosino); and the Alkek Center of Metagenomics and Microbiome Research (led by Petrosino with funding awards to Ganu and Aagaard).

https://www.bcm.edu/news/obstetrics-and-gynecology/genetic-unique-placental-microbiome
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2014-05-30 21:03:22 UTC
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Landmark study reveals first genetic snapshots of unique placental microbiome
Dr. Kjersti Aagaard, associate professor of obstetrics and gynecology in the section of maternal fetal medicine at Baylor and the Texas Children's Pavilion for Women.
The placenta is not as sterile as once thought. New research shows that the placenta harbors a unique, low abundant microbiome, said researchers from Baylor College of Medicine and Texas Children's Hospital.
Since our bodies are made up of billions of microbes, many of which
perform useful and vital functions, why would anybody expect that any
part of the human body including the placenta, be sterile?

This is a misconception of modern science that all germs and bacteria
are bad.

There are good bacteria and bad bacteria.
Obviously if good bacteria proliferate that is good and vice versa.

It would be nice if modern science could get past the very basics of
this new science and work up some workable theories on how to use the
information -- ie apart from fecal transplants which seems to be as
far as they've gotten.


Enquiring minds want to know

The pharmaceutical industry is based on myths and lies
http://www.pharmamyths.net/

Institutional Corruption of Pharmaceuticals and the Myth of Safe and
Effective Drugs
http://www.pharmamyths.net/files/JLME_ARTICLE_2013.pdf

Big Pharma Pockets $711 Billion in Profits by Price-Gouging Taxpayers
and Seniors
http://healthcareforamericanow.org/2013/04/08/pharma-711-billion-profits-price-gouging-seniors/

Pharmaceutical Companies Spent 19 Times More On Self-Promotion Than
Basic Research: Report
http://www.huffingtonpost.com/2012/08/09/pharmaceutical-companies-marketing_n_1760380.html
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2017-07-09 05:39:44 UTC
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Repeated antibiotic use alters gut's composition of beneficial microbes, study shows

SEP 13 2010
David Relman


Repeated use of an antibiotic that is considered generally benign, because users seldom incur obvious side effects, induces cumulative and persistent changes in the composition of the beneficial microbial species inhabiting the human gut, researchers at the Stanford University School of Medicine have found.

By a conservative estimate, something like 1,000 different varieties of microbes coexist harmoniously within a typical healthy person’s gut, said David Relman, MD, professor of medicine and of microbiology and immunology at the medical school and chief of the infectious diseases division at the Veterans Affairs Palo Alto Health Care System. Relman is the senior author of a paper, published online Sept. 13 in Proceedings of the National Academy of Sciences.

The study examined the effects of ciprofloxacin (trade name Cipro), an antibiotic that is widely prescribed for intestinal, urinary and a variety of systemic infections. In an earlier, short-term study, Relman’s group had concluded that people’s intestinal microbial communities seem to bounce back reasonably well within weeks after a five-day regimen of ciprofloxacin. This new study involved two courses of antibiotic administration, six months apart, and it revealed more-subtle, long-term effects of ciprofloxacin use — such as the replacement of multiple resident bacterial species by other, closely related varieties and the occasional complete eradication of a species.

The infrequent occurrence of easily visible side effects such as bloating and diarrhea from ciprofloxacin use has given rise to an assumption that the drug spares most beneficial gut-dwelling bacteria. Overall similarities between pre-regimen gut bacterial strains and their post-regimen replacements explain why such side effects aren’t typically seen after ciprofloxacin use. Still, the more nuanced differences between the pre-existing communities and those that appear in the wake of this repeated disturbance present a new set of problems, said Relman, who is also the Thomas C. and Joan M. Merigan Professor at the medical school. A bacterial species whose presence was lost or diminished may have been performing a valuable job — for example, secreting a protein that’s toxic to a particular pathogen — that is shirked by its replacement. The abandoned function might not be noticed until, perhaps, years later when the pathogen in question invaded the person’s gut.

While the study’s findings shouldn’t be interpreted to mean that ciprofloxacin is dangerous and should be avoided, Relman said, they do raise questions about possible long-term effects of antibiotic administration, in addition to concerns about spurring the evolution of drug-resistant organisms. The new findings underscore the desirability of finding ways to pinpoint not just which bacteria have been lost or whose numbers were diminished by an antibiotic, but also which important beneficial functions performed by the patient’s gut microbial community as a whole have been impaired — such as signaling cells of the intestinal lining, which are constantly turning over, to maintain an appropriate barrier against ingested toxic compounds, or secreting anti-inflammatory substances that may prevent allergic or autoimmune diseases.

For this study, the Stanford scientists collected more than 50 stool samples from each of three healthy adult females over a period of 10 months. Then they used advanced, molecular techniques to count the number of different microbial species represented in each sample, as well as relative population sizes of the different species in that sample.

Twice during this 10-month period, the researchers perturbed their subjects’ gut ecosystems by giving them five-day courses of ciprofloxacin at a standard dose. During the first course, overall bacterial populations in each subject — which had previously waxed and waned but, on the whole, been quite stable — plummeted and remained depressed for about a week. Roughly one-third to one-half of the resident species’ populations declined, with some disappearing entirely. A few originally less-abundant species grew in number, as they filled in the ecological niche abandoned by bugs adversely affected by the drug.

Within a week after the first course’s completion, two of the three subjects’ internal microbial ecosystems had largely returned to a state fairly similar to that before the regimen, as measured by the broad classes to which the microbial constituents belonged. One subject’s overall ecosystem, however, still had not recovered even by that rough measure a full six months later.

The second course of antibiotic administration produced a stronger effect. “Even the one subject whose gut bacterial community fully recovered after the first ciprofloxacin course experienced an incomplete recovery after the second one,” said Relman. The communities in the other two subjects partially recovered from the second course, but never returned to their original state. In essence, each subject’s community of gut-dwelling microbes shifted to a new, “alternative” state and remained in that state for at least two months after the second antibiotic course had been completed. Thus, all three subjects experienced significant and lasting changes in the specific membership of their internal microbial communities at the end of the 10-month study period.

“Ecologists have found that an ecosystem, such as a wildlife refuge, that is quite capable of rebounding from even huge occasional perturbations — forest fire, volcanic eruption, pests — may yet be undone by too rapid a series of such perturbations,” said Les Dethlefsen, PhD, a research scientist in Relman’s lab and the study’s first author. “In the same way, recurring antibiotic use may produce a cumulative effect on our internal microbial ecosystems with potentially debilitating, if as yet unpredictable, consequences.”

“It’s as if your beneficial bacteria ‘remember’ the bad things done to them in the past,” said Relman. “Clinical signs and symptoms may be the last thing to show up.”

The precise counts of gut-dwelling microbes in this study were made possible by a new technique, pioneered in recent years by Relman and others. The older method — growing the microbes in culture — simply doesn’t work for many species and, even when it does, rare species are often swamped by more common ones and don’t get counted. The new technique reads short, telltale DNA snippets that distinguish microbes both from human cells and one from another. This allowed the Stanford researchers to assess both the total number of different microbial varieties and the relative size of each variety’s population.

Similar techniques now make it possible to assess, before and after antibiotic administration, the abundance in a patient’s gut of microbial genes known to code for important functions performed by one or more members of the patient’s gut community, Relman said. In the future, if it becomes known that a key function has been impaired, clinicians might perhaps restore that function by prescribing specific probiotics or nutrients that encourage the return of appropriate beneficial bugs.

The research was supported by a National Institutes of Health Pioneer Award and by the Doris Duke Charitable Foundation. Information about the Departments of Medicine and of Microbiology and Immunology, which also supported the research, is available at http://medicine.stanford.edu and http://microimmuno.stanford.edu.

Bruce Goldman
By
BRUCE GOLDMAN
Bruce Goldman is a science writer for the medical school’s Office of Communication & Public Affairs.
Stanford Medicine integrates research, medical education and health care at its three institutions - Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children's Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.


https://med.stanford.edu/news/all-news/2010/09/repeated-antibiotic-use-alters-guts-composition-of-beneficial-microbes-study-shows.html
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