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Events, Immunology, Infectious Disease, Microbiology, Public Health

A look at our disappearing microbes

A look at our disappearing microbes

8146322408_5312e9deb2_zCould obesity, asthma, allergies, diabetes, and certain forms of cancer all share a common epidemiological origin? NYU microbiologist Martin Blaser, MD, thinks so – he calls these “modern plagues” and traces them to a diminished microbial presence in our bodies, caused by the overuse of antibiotics and the increased incidence of caesarian sections.

I attended a recent public lecture sponsored by UC Santa Cruz’s Microbiology and Environmental Toxicology department, during which the charismatic Blaser cited statistics about antibiotic use in childhood. Alarmingly, American children receive on average seventeen courses of antibiotics before they are twenty years old, taking a progressively bigger toll on their internal microbial ecosystems. We also have an unprecedented rate of c-sections – at nearly 33 percent. Babies delivered this way are deprived of contact with their mothers’ vaginal microbes, which in vaginal deliveries initiates the infant’s intestinal, respiratory, and skin flora. Breastfeeding has implications for beneficial bacterial transfer, too.

It’s not news that antibiotics are being overused – Stanford Medicine hosts an Antimicrobial Stewardship Program dedicated to this cause, and the CDC has been hosting a campaign for awareness about appropriate antibiotic use for several years, including their use in farm animals. (Seventy to eighty percent of antibiotic use takes place on farms to promote growth – that is, not for veterinary reasons.)

Overuse leads to antibiotic resistance, a serious problem. Meanwhile, research by Blaser and others – notably Stanford microbiologist David Relman, MD – has shown that abundant bacterial and viral life is essential to healthy bodies, and that imbalances in the microbial ecosystems that inhabit our gut play an important role in the chronic diseases of the modern age. Blaser said he is concerned that we’re going down a path where each generation has fewer and fewer species of microbes; part of his research is to compare human gut biodiversity in different parts of the globe, and people in remote areas of New Guinea have far more variety than those in Western nations.

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Applied Biotechnology, Bioengineering, Global Health, Microbiology, Stanford News

Foldscope beta testers share the wonders of the microcosmos

Foldscope beta testers share the wonders of the microcosmos

Foldscopes-TanzaniaChristmas came early for citizen-scientists who received the first batch of Foldscope build-your-own paper microscope kits from Stanford’s Prakash Lab over the last several months. These beta testers have begun sharing a variety of fascinating images, videos, tips and ideas on the Foldscope Explore website.

From this site, you can watch Foldscope videos of fluid pulsing through the brain of a live ant or the suction mechanism of a fly foot. One citizen scientist analyzes the structural differences between his brown and gray hair follicles. Another provides a tutorial on FBI bird-feather forensics. (Germophobes might want to skip the close-ups of a face mite or the fungus that grows in half-eaten yogurt cartons.)

Half the fun of receiving a Foldscope kit is the unboxing and building process, which has been captured in YouTube videos by Foldscope fans Christopher and Eric.


lens-mounterEach kit includes parts for building two microscopes, multiple lenses, magnets that attach a Foldscope to a smartphone camera lens, slide mounts, and a battery-powered light module. This allows users to view magnified images with the naked eye or projected on a wall. Photos or videos of Foldscope images can easily be captured and shared via smartphones.

For those of you who haven’t received your Foldscopes yet, rest assured that those who signed up on the beta test site will receive them soon. It’s taking longer than anticipated to build and ship 50,000 microscopes. (The gadget on the right was custom-designed to insert the tiny spherical ball lenses into the magnetic smartphone-mounting platform.)

For Foldscope updates, sharing and inspirations, bookmark Foldscope Explore.

Previously: Stanford bioengineer develops a 50-cent paper microscopeStanford microscope inventor invited to first White House Maker Faire, The pied piper of cool science tools and Free DIY microscope kits to citizen scientists with inspiring project ideas
Photo of Foldscope co-inventor Jim Cybulski and Tanzanian children building foldscopes by Manu Prakash; photo of lens mounting gadget by Kris Newby

Global Health, Infectious Disease, Microbiology, Public Health, Videos

'Tis the season for norovirus

'Tis the season for norovirus

The week before Thanksgiving, some kind of stomach bug, which I suspect was norovirus, spread like wildfire among my daughter’s daycare. Several of her classmates became sick and like dominos so did the parents, including us.

So I was more than sympathetic when I came across this video by John Green (of the vlogbrothers fame and author of “The Fault in Our Stars”) about his family’s Thanksgiving troubles with a norovirus infection that seems to have left no GI system untouched in their household.

Winter, from about November to April, is prime norovirus season. The treacherous illness, which as Green says “has amazing superpowers,” spreads when you come into contact with feces or vomit of an infected person. It can take less than a pinhead of virus particles to make this happen. Unlike other viruses, it can live on surfaces for surprising long periods, which is how a reusable grocery bag caused an outbreak among a girls soccer team in 2012. Plus, an infected person can continue to shed the virus for about three or four days after recovering. It’s possible to disinfect after an infection, but it’s a pretty intense job.

Given these characteristics it’s not surprising that this tiny virus (even by virus standards) causes about 20 million illnesses each year. Although for most people it’s a mild illness, for the very young,  old or those with compromised immune systems—it can be severe. About 56,000-71,000 people are hospitalized and 570-800 die from norovirus infections.

The situation is worse in developing countries, where, as Green points out, rehydration therapy is harder to come by for the most vulnerable. About 200,000 deaths are caused by norovirus infections in poor parts of the world.

In his typical funny and thoughtful style, Green talks about what lack of simple—and cheap—rehydration therapy means for many on our planet. It’s one more thing that it’s easy to take for granted, and one more thing to be thankful for.

Previously: Stanford pediatrician and others urge people to shun raw milk and products and Science weighs in on food safety and the three-second rule

Global Health, In the News, Infectious Disease, Microbiology, Public Health

Exploiting insect microbiomes to curb malaria and dengue

Original Title: Aa_FC2_23a.jpgEvery year, more than 200 million people are affected by malaria and 50 to 100 million new dengue infections occur. Now, a group of scientists from Johns Hopkins University may have found a novel way of curbing both diseases: by “vaccinating” mosquitos against the parasite that causes malaria and the virus that causes dengue. The researchers are using the bacteria Chromobacterium, which prevents the pathogens from effectively invading and colonizing mosquito guts.

As Science magazine reported last week:

Like humans and most other animals, mosquitoes are stuffed with microbes that live on and inside of them—their microbiome. When studying the microbes that make mosquitoes their home, researchers came across one called Chromobacterium sp. (Csp_P). They already knew that Csp_P’s close relatives were capable of producing powerful antibiotics, and they wondered if Csp_P might share the same talent.

In another experiment, done with mosquitoes that weren’t pretreated with antibiotics, Csp_P-fed mosquitoes were given blood containing the dengue virus and Plasmodium falciparum, a single-celled parasite that causes the most deadly type of malaria. Although a large number of the mosquitoes died within a few days of being infected by the Chromobacteriumthe malaria and dengue pathogens were far less successful at infecting the mosquitoes that did survive, the team reports today in PLOS Pathogens. That’s good news: If the mosquito isn’t infected by the disease-causing germs, it is less likely to be able to transmit the pathogens to humans.

The bacteria also inhibited growth of Plasmodium and dengue in lab cultures, indicating that Csp_P is producing compounds that are toxic to both pests. One possible application of these toxins is to develop treatment drugs for people already infected with malaria or dengue. Real-world applications of this research are many years in the future, but it hints at a whole new way of dealing with otherwise intractable diseases.

Previously: Close encounters: How we’re rubbing up against pathogen-packing pestsClosing the net on malaria and Fighting fire with fire? Using bacteria to inhibit the spread of dengue
Photo by Sanofi Pasteur

Immunology, Infectious Disease, Microbiology, Public Health, Research, Stanford News

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

cattleMake no mistake: Antibiotics have worked wonders, increasing human life expectancy as have few other public-health measures (let’s hear it for vaccines, folks). But about 80 percent of all antibiotics used in the United States are given to livestock – chiefly chickens, pigs, and cattle – at low doses, which boosts the animals’ growth rates. A long-raging debate in the public square concerns the possibility that this widespread practice fosters the emergence of antibiotic-resistant bugs.

But a new study led by Stanford bacteriologist Denise Monack, PhD, and just published in Proceedings of the National Academy of Sciences, adds a brand new wrinkle to concerns about the broad administration of antibiotics: the possibility that doing so may, at least  sometimes, actually encourage the spread of disease.

Take salmonella, for example. One strain of this bacterial pathogen, S. typhimurium, is responsible for an estimated 1 million cases of food poisoning, 19,000 hospitalizations and nearly 400 deaths annually in the United States. Upon invading the gut, S. typhimurium produces a potent inflammation-inducing endotoxin known as LPS.

Like its sister strain S. typhi (which  causes close to 200,00o typhoid-fever deaths worldwide per year), S. typhimurium doesn’t mete out its menace equally. While most get very sick, it is the symptom-free few who, by virtue of shedding much higher levels of disease-causing bacteria in their feces, account for the great majority of transmission. (One asymptomatic carrier was the infamous Typhoid Mary, a domestic cook who, early in the 20th century, cheerfully if unknowingly spread her typhoid infection to about 50 others before being forcibly, and tragically, quarantined for much of the rest of her life.)

You might think giving antibiotics to livestock, whence many of our S. typhi-induced food-poisoning outbreaks derive, would kill off the bad bug and stop its spread from farm animals to those of us (including me) who eat them. But maybe not.

From our release on the study:

When the scientists gave oral antibiotics to mice infected with Salmonella typhimurium, a bacterial cause of food poisoning, a small minority — so called “superspreaders” that had been shedding high numbers of salmonella in their feces for weeks — remained healthy; they were unaffected by either the disease or the antibiotic. The rest of the mice got sicker instead of better and, oddly, started shedding like superspreaders. The findings … pose ominous questions about the widespread, routine use of sub-therapeutic doses of antibiotics in livestock.

So, the superspreaders kept on spreading without missing a step, and the others became walking-dead pseudosuperspreaders. A lose-lose scenario all the way around.

“If this holds true for livestock as well – and I think it will – it would have obvious public health implications,” Monack told me. “We need to think about the possibility that we’re not only selecting for antibiotic-resistant microbes, but also impairing the health of our livestock and increasing the spread of contagious pathogens among them and us.”

Previously: Did microbes mess with Typhoid Mary’s macrophages?, Joyride: Brief post-antibiotic sugar spike gives pathogens a lift and What if gut-bacteria communities “remember” past antibiotic exposures?
Photo by Jean-Pierre

In the News, Microbiology, Public Health, Research

The end of antibiotics? Researchers warn of critical shortages

The end of antibiotics? Researchers warn of critical shortages

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Bacteria spark infection. Antibiotic kills most bacteria. Remaining bacteria evolve resistance. Second antibiotic wipes out all bacteria. Repeat. Repeat until, that is, there are no effective antibiotics, a scenario that looks increasingly likely, according to recent research from the Center for Molecular Discovery at Yale University led by Michael Kinch, PhD. Kinch now leads the Center for Research Innovation in Business at Washington University in St. Louis, which featured his work in a recent article:

The number of antibiotics available for clinical use, Kinch said, has declined to 96 from a peak of 113 in 2000. The rate of withdrawals is double the rate of new introductions, Kinch said. Antibiotics are being withdrawn because they don’t work anymore, because they’re too toxic, or because they’ve been replaced by new versions of the same drug. Introductions are declining because pharmaceutical companies are leaving the business of antibiotic use discovery and development.

Many of the major players like Pfizer, Eli Lilly, AstraZeneca and Bristol-Myers Squibb are no longer developing antibiotics, Kinch wrote in a recent article in Drug Discovery Today. In part, their disinterest is driven by a tight profit window. The drug approval process takes about 11 years, but a patent only provides 20 years of protection, leaving just nine years to recoup development costs, according to Kinch.

As outlined in the Washington University piece, at least two major initiatives are working to reverse this trend. The Infectious Diseases Society of America introduced the 10 x ’20 Initiative to spur efforts to create 10 new antibiotics by 2010. And Britain is sponsoring the Longitude Prize 2014, a £10 million award for a simple test that will quickly determine the type of bacteria causing an infection and therefore the most effective antibiotic.

Previously: Healthy gut bacteria help chicken producers avoid antibiotics, Free online course aims to education about “pressing public health threat” of antibiotic resistance and Side effects of long-term antibiotic use linked to oxidative stress
Photo by CDC Public Health Image Library

Immunology, Microbiology, Public Health, Research

Gut bacteria may influence effectiveness of flu vaccine

Gut bacteria may influence effectiveness of flu vaccine

flu_shotPast research has shown that the microbes living in your gut can dictate how body fat is stored, hormone response and glucose levels in the blood, which can ultimate set the stage for obesity and diabetes. Now new research suggests that the colonies of bacteria in our intestine play an important role in your body’s response to the flu vaccine.

In the study, Emory University immunologist Bali Pulendran, PhD, and colleagues followed up on a unexpected finding in a 2011 paper: the gene that codes for a protein called toll-like receptor 5 (TLR5) was associated with strong vaccine response. Science News reports that in the latest experiment:

[Researchers] gave the flu vaccine to three different groups: mice genetically engineered to lack the gene for TLR5, germ-free mice with no microorganisms in their bodies, and mice that had spent 4 weeks drinking water laced with antibiotics to obliterate most of their microbiome.

Seven days after vaccination, all three groups showed significantly reduced concentrations of vaccine-specific antibodies in their blood—up to an eightfold reduction compared with vaccinated control mice, the group reports online … in Immunity. The reduction was less marked by day 28, as blood antibody levels appeared to rebound. But when the researchers observed the mice lacking Tlr5 on the 85th day after vaccination, their antibodies seemed to have dipped again, suggesting that without this bacterial signaling, the effects of the flu vaccine wane more quickly.

Previously: The earlier the better: Study makes vaccination recommendations for next flu pandemic, Working to create a universal flu vaccine and Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease
Photo by Queen’s University

Applied Biotechnology, In the News, Infectious Disease, Microbiology, Public Safety

How-to manual for making bioweapons found on captured Islamic State computer

Black DeathLast week I came across an article, in the usually somewhat staid magazine Foreign Policy, with this subhead:

Buried in a Dell computer captured in Syria are lessons for making bubonic plague bombs and missives on using weapons of mass destruction.

That got my attention. Just months ago, I’d written my own article on bioterrorism for our newspaper, Inside Stanford Medicine. So I was aware that, packaged properly, contagious one-celled pathogens can wipe out as many people as a hydrogen bomb, or more. Not only are bioweapons inexpensive (they’ve been dubbed “the poor man’s nuke”), but the raw materials that go into them – unlike those used for creating nuclear weapons – are all around us. That very ubiquity, were a bioweapon to be deployed, could make fingering the perp tough.

The focal personality in my ISM article, Stanford emergency-medicine doctor and bioterrorism expert Milana Trounce, MD, had already convinced me that producing bioweapons on the cheap – while certainly no slam-dunk – was also not farfetched. “What used to require hundreds of scientists and big labs can now be accomplished in a garage with a few experts and a relatively small amount of funding, using the know-how freely available on the internet,” she’d said.

This passage in the Foreign Policy article rendered that statement scarily apropos:

The information on the laptop makes clear that its owner is a Tunisian national named Muhammed S. who joined ISIS [which now calls itself “Islamic State“] in Syria and who studied chemistry and physics at two universities in Tunisia’s northeast. Even more disturbing is how he planned to use that education: The ISIS laptop contains a 19-page document in Arabic on how to develop biological weapons and how to weaponize the bubonic plague from infected animals.

I sent Trounce a link to the Foreign Policy article. “There’s a big difference between simply having an infectious disease agent and weaponizing it,” she responded in an email. “However, it wouldn’t be particularly difficult to get experts to help with the weaponization process. The terrorist has a picked a good infectious agent for creating a bioweapon. Plague is designated as a Category A agent along with anthrax, smallpox, tularemia, botulinum, and viral hemorrhagic fevers. The agents on the Category A list pose the highest risk to national security, because they: 1) can be easily disseminated or transmitted from person to person; 2) result in high mortality rates and have the potential for major public-health impact; 3) might cause public panic and social disruption; and 4) require special action for public-health preparedness.”

Islamic State’s interest in weaponizing bubonic plague should be taken seriously. Here’s one reason why (from my ISM article):

In 1347, the Tatars catapulted the bodies of bubonic-plague victims over the defensive walls of the Crimean Black Sea port city now called Feodosia, then a gateway to the Silk Road trade route. That effort apparently succeeded a bit too well. Some of the city’s residents escaped in sailing ships that, alas, were infested with rats. The rats carried fleas. The fleas carried Yersinia pestis, the bacterial pathogen responsible for bubonic plague. The escapees docked in various Italian ports, from which the disease spread northward over the next three years. Thus ensued the Black Death, a scourge that wiped out nearly a third of western Europe’s population.

Previously: Microbial mushroom cloud: How real is the threat of bioterrorism? (Very) and Stanford bioterrorism expert comments on new review of anthrax case
Photo by Les Haines

Autoimmune Disease, Evolution, Immunology, Microbiology, Nutrition, Public Health, Stanford News

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

Civilization and its dietary (dis)contents: Do modern diets starve our gut-microbial community?

hunter-gatherer cafe

Our genes have evolved a bit over the last 50,000 years of human evolution, but our diets have evolved a lot. That’s because civilization has transitioned from a hunter-gatherer lifestyle to an agrarian and, more recently and incompletely, to an industrialized one. These days, many of us are living in an information-intensive, symbol-analyzing, button-pushing, fast-food-munching society. This transformation has been accompanied by consequential twists and turns regarding what we eat, and how and when we eat it.

Toss in antibiotics, sedentary lifestyles, and massive improvements in public sanitation and personal hygiene, and now you’re talking about serious shake-ups in how many and which microbes we get exposed to – and how many of which ones wind up inhabiting our gut.

In a review published in Cell Metabolism, Stanford married-microbiologist couple Justin Sonnenburg, PhD, and Erica Sonnenburg, PhD, warn that modern civilization and its dietary contents may be putting our microbial gut communities, and our health, at risk.

[S]tudies in recent years have implicated [dysfunctional gut-bug communities] in a growing list of Western diseases, such as metabolic syndrome, inflammatory bowel disease, and cancer. … The major dietary shifts occurring between the hunter-gatherer lifestyle, early Neolithic farming, and more recently during the Industrial Revolution are reflected in changes in microbial membership within dental tartar of European skeletons throughout these periods. … Traditional societies typically have much lower rates of Western diseases.

Every healthy human harbors an interactive internal ecosystem consisting of something like 1,000 species of intestinal microbes.  As individuals, these resident Lilliputians may be tiny, but what they lack in size they make up in number. Down in the lower part of your large intestine dwell tens of trillions of  single-celled creatures – a good 10 of them for every one of yours. If you could put them all on a scale, they would cumulatively weigh about four pounds. (Your brain weighs three.)

Together they do great things. In a Stanford Medicine article I wrote a few years back, “Caution: Do Not Debug,” I wrote:

The communities of micro-organisms lining or swimming around in our body cavities … work hard for their living. They synthesize biomolecules that manipulate us in ways that are helpful to both them and us. They produce vitamins, repel pathogens, trigger key aspects of our physiological development, educate our immune system, help us digest our food and for the most part get along so well with us and with one other that we forget they’re there.

But when our internal microbes don’t get enough of the right complex carbohydrates (ones we can’t digest and so pass along to our neighbors downstairs), they may be forced to subsist on the fleece of long carbohydrate chains (some call it “mucus”)  lining and guarding the intestinal wall. Weakening that barrier could encourage inflammation.

The Sonnenburgs note that certain types of fatty substances are overwhelmingly the product of carbohydrate fermentation by gut microbes. These substances have been shown to exert numerous anti-inflammatory effects in the body, possibly protecting against asthma and eczema: two allergic conditions whose incidence has soared in developed countries and seems oddly correlated with the degree to which the environment a child grows up in is spotlessly hygienic.

Previously: Joyride: Brief post-antibiotic sugar spike gives pathogens a lift, The future of probiotics and Researchers manipulate microbes in the gut
Photo by geraldbrazell

Global Health, Microbiology, Nutrition, Pediatrics, Research

Malnourished children have young guts

Malnourished children have young guts

Bangladeshi_childrenChildren who grow up malnourished lag behind healthy kids in terms of their height and weight. But a new study finds that they also fall behind in the bacteria in their guts. The findings may explain why weight gains are often temporary, and malnourished children remain underweight compared to healthy children in the long-term.

Babies get their first gut bacteria from their mothers during birth. As they eat new foods, the community that live in the intestines changes and matures throughout the first few years of life. By age three, an “adult” community has taken up residence in the gut, and helps the body to break down food and boost the immune system. But in malnourished children, scarce or low-quality food and infections from poor sanitation result in an underdeveloped bacterial community that looks more like the inhabitants of a young child.

A study by Sathish Subramanian and colleagues published yesterday in Nature finds that children living in a slum in Dhaka, Bangladesh who were treated for malnutrition with nutrient-dense foods, have a temporary improvement in their gut bacteria. But the community will regress back to a younger state months after the therapy stops. The results correlate with observations that nutritional therapy saves lives, but cannot correct problems such as stunted growth, learning disabilities and a weakened immune system.

Initially, the researchers took stool samples from healthy children of a range of ages from the same slum. By looking at the identity of the bacteria from their intestines, the researchers could figure out what types of bacteria live in the gut at different times. They then looked at the bacterial communities from children receiving therapeutic foods to treat malnutrition to determine the “age” of their communities throughout the course of their treatment.

In a commentary on the study, Elizabeth Costello, PhD, and David Relman, MD, researchers in the Department of Microbiology and Immunology at Stanford, compare the gut communities of malnourished children to a degraded environment, such as a clear-cut rainforest that becomes choked with weeds. Just as it is difficult to clear the weeds and restore the original rainforest trees, it is challenging to rehabilitate the gut communities of chronically malnourished children.

“Degraded communities can be resistant or resilient to change, and although host health can be restored, youth cannot,” write Costello and Relman. “Thus, an ounce of prevention is likely to be worth a pound of cure and, as with other types of developmental delays, early intervention may be crucial.”

The study’s authors suggest that monitoring the gut communities of impoverished children may be one way to kept tabs on their health, and to measure if experimental nutritional treatments are working. Just like height or weight, the age of the gut bacterial community may be one way to track a child’s growth and development.

Patricia Waldron is a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Malnourished infants grow into impoverished adults, study shows and Who’s hungry? You can’t tell by looking
Photo by Mark Knobil

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