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  • richardmitnick 8:02 am on December 29, 2016 Permalink | Reply
    Tags: , , , Microbiome, Weizmann group   

    From COSMOS: “Circadian rhythms and the microbiome” 

    Cosmos Magazine bloc

    COSMOS

    29 December 2016
    Richard G. “Bugs” Stevens
    Professor, School of Medicine
    University of Connecticut

    New research is beginning to show that the composition and activity of the microbiota exhibits a daily, or circadian, rhythmicity, just like we do.

    1
    Examples of the microbes associated with healthy human beings. Jonathan Bailey, NHGRI, CC BY

    We’ve known that bacteria live in our intestines as far back as the 1680s, when Leeuwenhoek first looked through his microscope. Yogurt companies use that information in the sales pitch for their product, claiming it can help keep your gut bacteria happy. The bacteria growing on our skin have also been effectively exploited to sell the underarm deodorants without which we can become, ahem, malodorous. Until fairly recently our various microbes were thought of as freeloaders without any meaningful benefit to our functioning as healthy human beings.

    However, that view has changed in a big way [Nature]over the last couple of decades.

    Interest in, and knowledge about, the microbiota has recently exploded. These highly diverse communities of microbes live in and on us in staggering numbers; researchers now estimate that a typical human body is made up of about 30 trillion human cells and 39 trillion bacteria.

    We now recognize they’re essential to our health, participating in many important physiological functions such as digestion and metabolism of foods, and immune responses and inflammation; disruption of the gut microbiota might then contribute to a variety of conditions including childhood asthma, obesity, colitis and colon cancer.

    New research is beginning to show that the composition and activity of the microbiota exhibits a daily, or circadian, rhythmicity [Cell], just like we do. This offers one pathway to explain a Pandora’s box of possible adverse health effects from aspects of modern life, such as eating late at night or too much electric light after sunset.

    The microbial daily routine

    The microbiota is primarily bacterial but also includes viruses and eukaryotes like yeast; the latter are much bigger and more complicated than bacteria, and have a structure similar to our own cells. The total DNA complement of the microbiota is termed the microbiome, and it’s what we study to learn about the inner workings of the microbiota.

    In this field’s early days, researchers took fecal samples from people to investigate the composition of the gut microbiome. Later they noticed that defining the microbiome from a sample taken in the morning was quite different from one taken in the evening: The gut microbiota was not static over the span of the day.

    Perhaps this was to be expected. Almost all life on Earth has an endogenous circadian rhythmicity that is genetically determined, but that also responds to changes in light and dark. For human beings, reliable changes occur between day and night in hunger, body temperature, sleep propensity, hormone production, activity level, metabolic rate and more.

    These findings on daily rhythmicity in microbiota have really piqued my interest because disruption of our circadian rhythmicity by electric light at night has been my research passion for several decades. As scientists investigate the links between our internal daily patterns, electric light and health, new information about the rhythmicity of our microbiome might hold clues about how this all works together.

    The crucial question is whether the microbes simply respond to their host human’s circadian rhythm or whether they can actually alter our rhythm somehow. And does this really matter anyway?

    Microbiota calling the shots

    A group of researchers from the Weizmann Institute in Israel have now used an array of remarkable DNA technologies to show that the gut microbiota changes location within the gut, and changes its metabolic outputs over the span of the 24-hour day, at least in mice. Amino acids, lipids and vitamins that the microbes release circulate in the host mouse’s blood. As the levels of these molecules in the blood changed throughout the day, they altered the expression of genes in the mouse’s liver that code for many metabolic enzymes.

    This is the first clear demonstration of the gut microbiota changing the circadian activity of an essential organ – in this case, the liver, which is the engine of our physiology and crucial to our health.

    2
    Changes in microbial movements and metabolite production over the course of the day influence host tissues. Thaiss et al/Cell 2016, CC BY

    The authors showed this link by administering an antibiotic to mice that kills much of the gut microbiota. Afterward they found significant changes in liver physiology. They could produce the same effect just by changing the feeding times of the mice; mice forced to eat only during the day showed different patterns of microbiota metabolites circulating in the blood than those allowed to eat at night, their natural active period.

    In addition, the authors showed the liver changes how it responds to an overdose of acetaminophen over the span of the day in response to signals from the microbiota in the gut. They used acetaminophen as an example of a drug that could damage the liver depending on how it’s broken down. Interestingly, an overdose was less toxic at the beginning of the day, dawn, and most toxic at the end of the day, dusk.

    They concluded that the microbiota regulates how effectively the liver can detoxify over the course of the day. The authors argue that this finding can be extrapolated to apply to metabolism of drugs in general, including chemotherapeutic agents we use to treat disease. If so, then the time of day that a medication is administered could have a big impact on its effectiveness, and on the severity of its adverse side effects.

    This work has exciting implications. Understanding how time of day matters might allow for better treatment of disease, and for prevention of maladies like obesity, metabolic syndrome and perhaps other serious conditions.

    Technology drives the science

    The findings described by the Weizmann group were made possible by advances in the technology of DNA research. As so often happens, scientific insights follow on technological development.

    This is particularly true in the science of DNA. In order to count trillions of microbes as well as distinguish among hundreds of different species, there are four broad requirements: conceptual development, sequencing machines, analytic approaches and supercomputers to conduct the near hopelessly complex statistical analyses. Each of these has advanced to an extent that now studies like the one from the Weizmann Institute are achievable.

    The key conceptual breakthrough in analyzing the microbiome came with the recognition that the complex array of so many different organisms living together in a community may not be reducible. In other words, it doesn’t appear possible to separate out only one bacterial species from the group, and understand how it functions in isolation. The community works as a whole. For example, some of its members are bacteria that cannot absorb iron, which is necessary for growth. They require iron-binding molecules made by other members of the community to survive. So you can’t grow this guy in a Petri dish by itself.

    3
    Shift work might have effects on you and your microbiota. Woman image via shuterstock.

    Gut and rhythm

    The findings of the new study from Israel, which extends previous exciting work in this area, are relevant to humans for many reasons. For example, people who must take antibiotics for extended periods, or shift workers who eat at the “wrong” time of day, may be at risk via these microbiome pathways. In both instances, there will be changes in their metabolism that could lead, perhaps, to higher risk of obesity and metabolic syndrome, both of which have been shown to be in excess in night workers.

    A root cause of these human health issues we see on the macro scale may be our gut microbiota and whether or not it is happy.

    See the full article here .

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  • richardmitnick 3:40 pm on May 13, 2016 Permalink | Reply
    Tags: , , Microbiome, New National Microbiome Initiative   

    From LBL: “Berkeley Lab Participates in New National Microbiome Initiative” 

    Berkeley Logo

    Berkeley Lab

    May 13, 2016
    Dan Krotz
    510-486-4019
    dakrotz@lbl.gov

    The Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) will participate in a new National Microbiome Initiative launched today by the White House Office of Science and Technology Policy.

    The initiative, announced at an event in Washington, D.C., will advance the understanding of microbiome behavior and enable the protection of healthy microbiomes, which are communities of microorganisms that live on and in people, plants, soil, oceans, and the atmosphere. Microbiomes maintain the healthy function of diverse ecosystems, and they influence human health, climate change, and food security.

    The National Microbiome Initiative brings together scientists from more than 100 universities, companies, research institutions, and federal agencies. The goal is to investigate fundamental principles that govern microbiomes across ecosystems, and develop new tools to study microbiomes.

    Berkeley Lab is well positioned to contribute to the national effort thanks to Microbes to Biomes, a Lab-wide initiative designed to understand, predict, and harness critical microbiomes for energy, food, environment, and health. The initiative involves scientists across Berkeley Lab in biology, environmental sciences, genomics, systems biology, computation, advanced imaging, material sciences, and engineering.

    “It’s exciting to see this coordinated National Microbiome Initiative launched. It is very much in line with our interdisciplinary vision for Microbes-to-Biomes and our goals of building a functional understanding of Earth’s microbiomes,” says Eoin Brodie, deputy director of Berkeley Lab’s Climate and Ecosystem Sciences Division.

    In addition, Brodie is the corresponding author of an editorial published* today in the journal mBio that calls for a predictive understanding of Earth’s microbiomes to address some the most significant challenges of the 21st century. These challenges include maintaining our food, energy, and water supplies while improving the health of our population and Earth’s ecosystems. Trent Northen, director of Berkeley Lab’s Environmental Genomics and Systems Biology Division, and Mary Maxon, Biosciences Area principal deputy, are co-authors of the editorial.

    More about Berkeley Lab’s Microbes to Biomes Initiative


    Access mp4 video here .
    Berkeley Lab’s Microbes to Biomes initiative is designed to reveal, decode and harness microbes.

    Microbes to Biomes brings together teams of Berkeley Lab scientists to discover causal mechanisms governing microbiomes and accurately predict responses. The goal is to harness beneficial microbiomes in natural and managed environments for a range of applications, including terrestrial carbon sequestration, sustainable growth of bioenergy and food crops, and environmental remediation.

    The initiative, which aims to bridge the gap from microbe-scale to biome-scale science, takes advantage of Berkeley Lab’s capabilities, ranging from biology, environmental sciences, genomics, systems biology, computation, advanced imaging, materials sciences, and engineering.

    Berkeley Lab scientists are developing new approaches to monitor, simulate, and manipulate microbe-through-biome interactions and feedbacks. They’re also creating controlled laboratory “ecosystems,” which will ultimately be virtually linked to ecosystem field observatories. The initial goal is to build a mechanistic and predictive understanding of the soil-microbe-plant biome.

    More about the mBio editorial

    1
    The potential impact of a unified Microbiome initiative to understand and responsibly harness the activities of microbial communities. (Credit: Diana Swantek, Berkeley Lab)

    The mBio paper makes the case that given the extensive influence of microorganisms across our biosphere—they’ve shaped our planet and its inhabitants for over 3.5 billion years—and new scientific capabilities, the time is ripe for a cross-disciplinary effort to understand, predict, and harness microbiome function to help address the big challenges of today.

    This effort could draw on rapidly improving advances in gene function testing as well as precision manipulation of genes, communities, and model ecosystems. Recently developed analytical and simulation approaches could also be utilized.

    The goal is to improve prediction of ecosystem response and enable the development of new, responsible, microbiome-based solutions to significant energy, health, and environmental problems.

    The mBio editorial was authored by eleven scientists from several institutions. The Berkeley Lab co-authors were supported by the Department of Energy’s Office of Science.

    Science editorial:
    Toward a Predictive Understanding of Earth’s Microbiomes to Address 21st Century Challenges

    See the full article here .

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  • richardmitnick 2:57 pm on August 9, 2015 Permalink | Reply
    Tags: , Microbiome,   

    From Chicago: “Looking closer at role of microbiome” 

    U Chicago bloc

    University of Chicago

    August 2015
    The University of Chicago Magazine.
    Lydialyle Gibson, courtesy of the University of Chicago Magazine
    Photo by Mark Lopez, Argonne National Laboratory

    1
    Jack Gilbert and colleagues study bacteria’s broad influence

    There’s a story that Assoc. Prof. Jack Gilbert, a microbial ecologist at UChicago and Argonne National Laboratory, likes to tell about a bacterium called Enterococcus faecalis. It’s sort of a love story gone wrong.

    Squat and vaguely jellybean-like, measuring about three microns long, E. faecalis lives in the human gastrointestinal tract. Under normal circumstances, the relationship is friendly. It’s close. It’s what microbiologists call commensal, a term whose Latin etymology conjures up togetherness and a shared dinner table.

    “In its original state, just living inside your gut, this bug is totally harmless,” Gilbert says. “In fact, it’s beneficial. It helps train your immune system.” Your body wants it there, needs it there, has evolved to live with it. “It’s a natural part of your gut’s flora, your ecosystem.”

    All that can change, though, when a person goes in for gastrointestinal surgery. Like, for instance, to remove part of the colon and stitch the remaining pieces back together, a routine treatment for colon cancer. Afterward, some patients develop what’s called an anastomotic leak. The seam where the bowel has been rejoined breaks open, and fluids from the intestine begin seeping into the body. It’s a rare complication, but it can be disastrous, sometimes fatal. Even after years of increasingly better materials—glues, staples, stronger stitches—and increasingly precise surgical techniques, anastomotic leak persists. Some surgeons opt to avoid the risk altogether by performing a colostomy that, unpleasantly, diverts fecal matter into an external bag.

    The culprit, it turns out, is usually not the stitches or the surgeon; instead, it’s a particular strain of the otherwise commensal E. faecalis. In a study published this past May, Gilbert and John Alverdy, the Sara and Harold Lincoln Thompson Professor of Surgery, found that the bacterium creates small holes in the intestine at the surgical site, degrading the tissue and weakening the connection. In rats with anastomotic leaks, the abundance of E. faecalis ballooned 500-fold. “It becomes like a swarm of locusts,” Gilbert says of the microbe. “And it swarms directly to the site of damage in the cell wall, grabs hold of it, and starts to break down the collagen that the body is trying to use to repair the cell damage. It’s like going to the scaffolding on a new building and just ripping it apart. And the building falls down.”

    But why? What makes this friendly bug turn against its host? The answer, Gilbert says, underlines an increasingly inescapable need to reimagine the way medicine is practiced. Not just surgery, but all medicine. And—now that he’s talking about it—not just medicine, but modern life more broadly. The cities we build, the buildings we work in, the food we eat, the homes we keep, the environments where we live our lives and raise our children. All these factors affect the microbes living inside us, which in turn, scientists are discovering, can influence everything from obesity to Alzheimer’s to asthma.

    Unraveling influence of microbiome

    Humans are vastly outnumbered in their own bodies. For every human cell, there are 10 cells of bacteria. But until they’re born, babies are sterile. They leave the womb and pass through the birth canal, where they’re colonized by their mothers’ microbiota. After that, children pick up bacteria everywhere they go: from their parents and siblings and other people, from pets, food, clothes, floors, furniture, toys, plants, trees, dirt, and the air all around them. By the time children learn to walk, they’re enveloped, inside and out, by a massive, invisible kaleidoscope of microorganisms, 100 trillion or so. Those microbes—mostly bacteria but also some viruses and fungi—live in our mouths and blanket our skin; they congregate in our nasal passages and ear canals and on the surface of our eyes. More than anywhere else, they inhabit our digestive systems.

    Taken together, these organisms are called the microbiome, and they are so pivotal to our health, both its function and dysfunction, that scientists have begun thinking of them as another organ. Indeed, about three pounds of every person’s biomass is microbial; that’s roughly the same weight as the human brain. Friendly microbes living happily in our bodies help train our immune system, help digest our food and absorb nutrients from it, and help keep pathogens at bay. But the role that E. faecalis plays in anastomotic leaks is only one example of what can happen when this complex and dynamic community of organisms falls out of balance.

    UChicago scientists, including Gilbert, are researching the ways in which “dysbiosis,” a microbial imbalance inside the body, can lead to food allergies and inflammatory bowel disorders. Pathologist Alexander Chervonsky studies the link between an absence of certain microbes in the gut and the onset of type 1 diabetes and other autoimmune disorders. He’s also examining how the differing composition of male and female microbiomes may at least partly explain why autoimmune disorders strike women more often than men. Pediatrician Stacy Kahn has looked at how fecal transplants, which transfer gut microbes from one person to another, can be used to treat recurrent Clostridium difficile infections in children.

    Geneticist Carole Ober is working to unravel the microbial influence on asthma. For decades, Ober has studied the Hutterites of South Dakota and the Amish of northern Indiana, two groups with nearly identical genetic ancestry—both are Anabaptists who live on communal farms—but strikingly divergent childhood asthma rates. At 15 percent, the Hutterites’ rate exceeds the national average, while the Amish Ober studies have almost no asthma at all. Her recent research points to the seemingly protective effects of dust, and the microbes within it, found in Amish homes. New research, not yet published, on which Gilbert is a collaborator, also points, he says, to differing traditional practices that have Amish children working out in the barns at a much earlier age than the Hutterite children.

    Some of the most promising discoveries have come in the realm of allergies. Particularly food allergies—peanuts, tree nuts, fish, shellfish, milk, eggs, wheat, and soy are the big ones—which have risen dramatically, and somewhat mysteriously, over the past two decades. Last year, UChicago immunologist Cathryn Nagler, the Bunning Food Allergy Professor, identified a particular class of gut bacteria, Clostridia, that seems to protect the body against allergies by preventing allergens from getting into the bloodstream.

    Limitless research potential

    Microbiome research is still in its early stages. A decade or more ago, genetics seemed like the key to understanding our biological fates. Find the gene and you’ll find the disease. But the picture turns out to be much more complicated. Genes are important, but not by themselves determinative. And the same DNA-sequencing technology that made possible the map of the human genome also made it possible to sequence and analyze the microbes in the human body. A whole new universe sprang into view.

    The promise seems so limitless. At a panel discussion on the microbiome during Alumni Weekend, Gilbert cautioned people not to get ahead of the science. “We can’t go in thinking this is the answer to everything.” So little is known, and the complexity is almost unimaginably vast. Mouse models are a long way from human clinical trials.

    Still. Alverdy, who collaborated with Gilbert on the E. faecalis study and has spent more than 20 years analyzing the behavior of intestinal bacteria, says this research is perhaps the most significant happening now. “I believe that understanding the microbes is how we’re going to save the earth,” he says. “Really. Truly. They’re that important.”

    See the full article here.

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  • richardmitnick 11:44 am on January 2, 2015 Permalink | Reply
    Tags: , Microbiome,   

    From Yale: “Research explains how we live in harmony with friendly gut bacteria” 

    Yale University bloc

    Yale University

    January 1, 2015
    Bill Hathaway

    Stability in the composition of the hundred trillion bacterial cells in the human gastrointestinal tract is crucial to health, but scientists have been perplexed how our microbiota withstands an onslaught of toxins, dietary changes, and immune response to infections or antibiotics with little change.

    h

    Research from Yale published in the Jan. 2 issue of the journal Science identifies a strategy that commensal, or non-harmful, gut bacteria employ to preserve this stable relationship with their host during inflammation.

    “It has been a puzzle that many immune responses target all bacteria,” said Andrew Goodman, assistant professor of microbial pathogenesis and a member of the Microbial Sciences Institute at Yale’s West Campus. “Yet healthy individuals maintain the same beneficial microbes for decades even when exposed to a host of environmental disturbances.’’

    Research has shown that disruptions in the gut microbiome can lead to severe health consequences, including obesity, recurrent infections, and diseases such as irritable bowel syndrome. Instability in the microbiome has been linked to diseases as diverse as autism and cancer. Doctors may one day be able to manipulate the microbiome to treat patients, but scientists first need to understand the molecular machinery of the vast gut microbiome, which contains a hundred times more genes than the human genome.

    The new study represents a first step, Goodman said. The Yale team found that in mice and humans, microbiome stability is maintained by a single gene that allows bacteria to resist high levels of inflammation-associated antimicrobial peptides. Commensal bacteria that lack this mechanism were promptly removed from the gut during inflammation in mice.

    “We were surprised that a single factor could have such a large effect,” Goodman said. “This study opens the door for new approaches to understand how commensal bacteria interact with their hosts.”

    Thomas W. Cullen of Yale is the lead author of the study.

    Primary funding for the work was provided by the National Institutes of Health.

    See the full article here.

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  • richardmitnick 2:27 pm on December 10, 2014 Permalink | Reply
    Tags: , , , Microbiome,   

    From NOVA: “New Antibiotic Found in Bacteria from the Vaginal Microbiome” 

    PBS NOVA

    NOVA

    12 Sep 2014
    Tim De Chant

    Researchers announced yesterday that they had discovered a new molecule that could be a promising antibiotic capable of killing Staphylococcus aureus, a bacteria that can cause dangerous skin infections. That’s good news, especially since drug resistance among harmful bacteria is evolving at a rapid pace. But what makes this molecule unique is it’s source—our bodies.

    s
    Scanning electron micrograph of S. aureus; false color added.

    Microbiologists have long suspected that new classes of drugs—antibiotics in particular—could be lurking in our microbiomes, where various bacteria duke it out for dominance of a particular niche.

    m
    Lactobacillus bacteria, which produce the antibiotic lactocillin

    This new molecule, called lactocillin, was discovered in a sweep of a database containing genes culled from our microbiome. Michael Fischbach, a microbiologist at the University of California, San Francisco, and his team then traced the genes responsible for lactocillin back to bacteria living in the vagina.

    Erika Check Hayden, reporting for Nature News:

    “We used to think that drugs were discovered by drug companies and prescribed by a physician and then they get to you,” Fischbach says. “What we’ve found here is that bacteria that live on and inside of humans are doing an end-run around that process; they make drugs right on your body.”

    Fischbach’s team then purified one of these: a thiopeptide made by a bacterium that normally lives in the human vagina. The researchers found that the drug could kill the same types of bacteria as other thiopeptides — for instance, Staphylococcus aureus, which can cause skin infections. The scientists did not actually show that the human vaginal bacteria make the drug on the body, but they did show that when they grew the bacteria, it made the antibiotic.

    Fischbach told Check Hayden that, at the current time, he’s not interested in turning lactocillin into a bonafide drug. Instead, he’s going to continue plumbing the depths of these huge databases of microbiome genes, hoping to find even more intriguing and promising candidates.

    See the full article here.

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    NOVA is the highest rated science series on television and the most watched documentary series on public television. It is also one of television’s most acclaimed series, having won every major television award, most of them many times over.

     
    • The Sustainabilitist 10:50 am on January 1, 2015 Permalink | Reply

      Turning an antibiotic into a drug just strike us as the wrong course of action. For one, the skin infection could be caused not by the S. aureus themselves, but by the abnormal concentration of them. Also, instead of focusing on supplementing bacteria that produce antibiotic in a clinical manner, more focus should be put into investigating how these antibiotics are produced in the natural environment. The behavioral approach has proven countless time to be much less invasive than clinical interventions, so maybe marketisation of drugs has another hidden agenda.

      Like

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