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Microbiology

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

Health Policy, Infectious Disease, Microbiology, Public Health, Stanford News

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Dr. Milana Trounce, M.D. teaches a class on the the risks of bioterror at the Stanford School of Medicine. Photo taken on Monday, April 21, 2014. ( Norbert von der Groeben/ Stanford School of Medicine )

“What if nuclear bombs could reproduce? Get your hands on one today, and in a week’s time you’ve got a few dozen.”

That’s the lead sentence of a feature article I just wrote for Inside Stanford Medicine. The answer is, bombs can’t reproduce. But something just as potentially deadly – and a whole lot easier to come by – can, and does.

What I learned in the course of writing the feature, titled “How contagious pathogens could lead to nuke-level casualties” (I encourage you to take a whack at it), was bracing. Stanford surgeon Milana Trounce, MD, who specializes in emergency medicine, has been teaching a course that pulls together students, faculty and outside experts from government, industry and academia. Her goal is to raise awareness and inspire collaborations on the thorny multidisciplinary problems posed by the very real prospect that somebody, somewhere, could very easily be producing enough killer germs to wipe out huge numbers of people – numbers every bit as large as those we’ve come to fear in the event of a nuclear attack.

Among those I quote in the article are infectious-disease expert David Relman, MD, and biologist/applied physicist Steven Block, PhD, both of whom have sat in on enough closed-door meetings to know that bioterrorism is something we need to take seriously.

Not only do nukes not reproduce. They don’t leap from stranger to stranger, or lurk motionless in midair or on fingertips. Nor can they be fished from soil and streams or cheaply conjured up in a clandestine lab in someone’s basement or backyard.  One teaspoon of the toxin produced by the naturally occurring bacterial pathogen Clostridium botulinum is enough to kill several hundreds of thousands of people. That’s particularly scary when you consider that this toxin – better known by the nickname “Botox” -  is already produced commercially for sale to physicians who inject it into their patients’ eyebrows.

As retired Rear Adm. Ken Bernard, MD, a former special assistant on biosecurity matters to Presidents Bill Clinton and George W. Bush and a guest speaker for Trounce’s Stanford course, put it: “Who can be sure there’s no off-site, illegal production? Suppose a stranger were to say, ‘I want 5 grams — here’s $500,000’?

That’s five grams, as in one teaspoon. As I just mentioned, we’re talking hundreds of thousands of people killed, if this spoonful were to, say, find its way into just the right point in the milk supply chain (the point where loads of milk from numerous scattered farms get stored in huge holding tanks before being parsed out to myriad delivery trucks). That’s pretty stiff competition for a hydrogen bomb. For striking terror into our hearts, the only thing bioweapons lack is branding – nothing tops that mushroom-cloud logo.

Previously: Stanford bioterrorism experts comments on new review of anthrax case and Show explores scientific questions surrounding 2001 anthrax attacks
Photo of Milana Trounce by Norbert von der Groeben

Applied Biotechnology, Bioengineering, Global Health, Microbiology, Science

The pied piper of cool science tools

The pied piper of cool science tools

Kid-scopeWhen Stanford bioengineer Manu Prakash, PhD, and his students set out to solve a challenging global health problem, the first order of business is to have fun.

“We’re a curiosity-driven lab,” says Prakash, as he sits in his office overflowing with toys, gadgets, seashells and insect exoskeletons.

In the last month, Prakash introduced two new cool science tools — a 50-cent paper microscope and a $5 programmable kid’s chemistry set. The response from fellow science lovers, compiled on this Storify page, has been amazing.

Already, 10,000 kids, teachers, health workers and small thinkers from around the globe have signed up to receive build-your-own-microscope kits. Thousands more have sent us e-mails describing the creative ways they’d use a microscope that they could carry around in their back pockets.

For the love of science, here are a few of these inspirational e-mails:

I would love to have one. I’m only in 6th grade but I love science. I hope to visit the moon one day. — Raul

I am an electrical engineer from Kenya and have never used a microscope in all my life. But what I would really like to do is to avail the foldscope to students in a primary school that I am involved in mentoring. This apart from hopefully inspiring them in the wonders of science, would enable the students see the structure of the mosquito proboscis, a malaria-spreading agent in this part of the world. I would also like to look at the roots of mangrove trees and see the structure that enables them to keep sea water salts out. — Macharia Wanyoike

This is brilliant! I am in science and nanotechnology education and my wish is for South African rural children, Namibia, Zimbabwe, Botswana to all have these microscopes! It will be amazing. — Professor Sanette Brits, University of Limpopo, South Africa

waterbearI am studying how magnetic fields at different frequencies affect water bears. They are very difficult to find and it would be great if I had a tool to help me find them that is  portable while searching for them. I have digital motic microscope phase contrast and darkfield microscopes but nothing portable. — Edward W. Verner (Water bear shown to the left.)

I could use it to check if patients have scabies. Or if I were visiting remote monasteries in the Himalayas where they have outbreaks. I’d definitely pack it. For myself I’d use it on nature walks. GREAT ACCOMPLISHMENT for mankind. Congratulations. — Linda Laueeano, RN

Hi! I am a high school student from South Korea. While I was searching for interesting project, I saw your video. It was very amazing and I can’t believe that only one dollar can save hundreds and thousands people who were suffering from malaria and other diseases that can be found by your “foldscope”. I really love to study about your project and I had already read your thesis. Truly, it was hard to understand everything, but I really tried hard and I discussed this issue for more than a week with my science club. We are group of 10 people and we are eager to do this project. Also I really appreciate you to do this wonderful thing for poor kids in many other countries. Thanks. — Joung Yeon Park

I am assisting a K-12 community school with creating a STEAM Innovation Knowledge HUB, as they are trying to move their Common Core Curriculum into a STEM to STEAM driven program. It would be great to receive several Foldscopes or be able to purchase. Please contact me ASAP. Congratulations on a great new support product and great innovation. Thank you, smile. — Dr. Dion N. Johnson, Wayne State University

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

Discovered: Why so many people with schistosomiasis (there’s a lot of them) are so vulnerable to bacterial co-infection

Discovered: Why so many people with schistosomiasis (there's a lot of them) are so vulnerable to bacterial co-infection

More than a billion people worldwide – almost all of them in developing countries – are infected by worm-like parasitic organisms called helminths. Organisms making up just a single genus of helminth, Schistosoma, account for one-quarter of those infections, which damage different body parts depending on what schistosomal species is doing the infecting. Some go for the lung. Others (card-carrying members of the species Schistosoma haematobium) head for the urinary tract, with one in ten infected patients suffering severe physical consequences.

People with schistosomiasis of the urinary tract are especially vulnerable to bacterial co-infections. Worse, these co-infections exacerbate an already heightened risk of bladder cancer in infected individuals, it’s believed. Unfortunately, considering the massive numbers of cases, surprisingly little is understood about the molecular aspects of the infection’s course.

A big reason for that relative ignorance has been the absence of an effective animal model enabling the detailed study of urinary-tract schistosomiasis. A couple of years ago, Stanford schistosomiasis expert Mike Hsieh, MD, PhD, developed the world’s first decent mouse model for the disease, allowing him to explore the molecular pathology that occurs early in the course of infection. Now, in a just-published study in Infection and Immunity, Hsieh has put that mouse model to work in coaxing out the cause of the curious collegiality of S. haematobium and co-infecting bacteria.

The secret, the scientists learned, is that S. haemotobium infection induces a spike in levels of a circulating immune-system signaling protein, or cytokine, called IL-4. That excess, in turn, results in a drop in the number and potency of a subset of immune cells that are important in fighting off bacterial infections. The discovery opens a pathway toward the development of new, non-antibiotic drug treatments for co-infected patients that won’t wreak havoc with their microbiomes, as antibiotics typically do.

Previously: Is the worm turning? Early stages of schistosomiasis bladder infection charted, Neglected story of schistosomiasis in Ghana, as told in a  sand animation and A good mouse model for a bad worm

Immunology, Mental Health, Microbiology, Public Health

Examining how microbes may affect mental health

Examining how microbes may affect mental health

Over on the NIH Director’s Blog today, there’s an interesting post about research efforts aimed at determining how the colonies of bacteria in our gut could play a role in mental health. As described in the piece, past research has shown there are a number of ways microbes can influence our thoughts, behavior and mood:

First of all, and perhaps most obviously, gut bacteria are engaged in a wide range of biochemical activities, producing metabolites that are absorbed into the human bloodstream. But there are other connections. One species of bacterium, for example, sends messages that are carried via the vagus nerve, which links the intestinal lining to the brain. When this species is present, the mice demonstrate fewer depressive behaviors than when it’s absent. Another bacterium plays an enormous role in shaping the immune system, which goes awry in many neurological diseases. This species of bacterium interacts directly with the immune system’s regulatory T-cells to provide resistance against a mouse version of multiple sclerosis, a progressive disease in which the immune cells damage the central nervous system by stripping away the insulating covers of nerve cells.

As Stanford microbiologist and immunologist Justin Sonnenburg, PhD, commented in a past entry on Scope, “There’s no doubt about it. These microbes are influencing every aspect of our neurobiology. There’s a direct connection between the microbes inside our gut and the central nervous system. They’re influencing our behavior, our moods, even our decisions.”

Previously: Could gut bacteria play a role in mental health?Study shows probiotic foods may alter metabolism, but can they boost your health? and Study shows intestinal microbes may fall into three distinct categories

Applied Biotechnology, Microbiology, Patient Care, Research, Stanford News, Surgery

Staphylococcus aureus holes up in upper nasal cavity, study shows

Staphylococcus aureus holes up in upper nasal cavity, study shows

nostrilsA posse led by Stanford microbe sleuth and microbiologist David Relman, MD, has apprehended Staphylococcus aureus, one of the most notorious sources of serious infections, lurking in formerly unsuspected nasal hideaways. The discovery may explain why attempts to expunge S. aureus from the bodies of hospitalized patients being readied for surgery often meet with less than perfect results.

About one in three of us are persistent S. aureus carriers, and another third of us are occasional carriers. This bacterial shadow, which abounds on skin (especially the groin and armpits) and is quite at home in the nose, does us no harm most of the time. But if it gets into the bloodstream or internal organs, it can cause life-threatening problems such as sepsis, pneumonia and endocarditis (infection of heart valves). That makes S. aureus not such a good thing to be coated with if you’re about to have your skin punctured by a catheter or pierced by a scalpel.

This is exacerbated by the all-too-frequent presence, particularly in hospital settings, of S. aureus strains resistant to an entire family of antibiotics related to methicillin. In 2011, more than 80,000 severe methicillin-resistant S. aureus infections and more than 11,000 related deaths occurred in the U.S. alone, along with a much higher number of less-severe such infections.

In a study just published in Cell Host & Microbe, Relman – who pioneered the use of ultra-high-volume gene-sequencing techniques to sort out the thousands of species of microbes that communally inhabit our skin, orifices and innards – and his team used this method to show that mucosal sites way up high in our nose, where standard S. aureus-elimination techniques may not reach, can serve as reservoirs for S. aureus. That may, at least in part, explain why efforts to rid patients of this potentially nasty bug have so often fallen short of the mark, as I noted in my news release about the new findings:

Rigorous and somewhat tedious regimens for eliminating S. aureus residing on people’s skin or in their noses do exist, but it’s typically a matter of weeks or months before the bacteria repopulate those who are susceptible. The new study offers a possible reason why this is the case.

Previously: Cultivating the human microbiome, Anti-plaque bacteria: Coming soon to your toothpaste? and Eat a germ, fight an allergy
Photo by OakleyOriginals

Genetics, Microbiology, Research, Stanford News, Transplants

Stanford study in transplant patients could lead to better treatment

Stanford study in transplant patients could lead to better treatment

To keep a patient healthy following an organ transplant, doctors must prescribe the right balance of immune-system-supressing drugs: The medications need to be strong enough to prevent rejection of the foreign body but not leave the immune system at risk for infection. Now, a study by Stanford scientists has pinpointed a little-known virus that spreads when these immunosuppressant drugs take effect. The anellovirus, first identified in 1997, could be a barometer of immune system strength, thereby informing more precise and less reactive treatment for transplant recipients.

Lead author Stephen Quake, PhD, and collaborators isolated specific DNA fragments floating in the blood plasma of 96 heart and lung transplant patients using a technique of genomics, of which Quake is a pioneer. The team studied how the drugs affected the body’s microbiome, or collection of bacteria, fungi and viruses.

As described in a release, the researchers found that “lower levels of anellovirus suggest a stronger immune system and an elevated risk of organ rejection, while higher levels of anellovirus suggest a weaker immune system with a corresponding shift in risk toward vulnerability to infection.”

Hannah Valentine, MD, professor of cardiovascular medicine and senior associate dean for diversity and leadership at the School of Medicine, remarked, “These findings suggest an effective tool to individualize the monitoring and, ultimately, the treatment of rejection. In the future, this could allow us to safely lower the doses of immunosuppressive drugs patients receive, thereby avoiding devastating side effects.”

Previously: Extracting signal from noise to combat organ rejectionWhole-genome fetal sequencing recognized as one of the year’s “10 Breakthrough Technologies” and New techniques to diagnose disease in a fetus

Microbiology, Research

Microbes in your mouth could be a distinguishing characteristic

smile2Oral hygiene still matters (keep your floss handy), but did you know that your mouth’s microbial signature may also play a role in your dental and gum health? That’s according to a recent study that found that among hundreds of species of microbes present in a person’s mouth, only two percent were shared among the four ethnic groups studied.

What’s more, the researchers found ethnicity-distinctive mouth microbial communities among the non-Hispanic black, white, Chinese and Latino populations who participated in the study.

From a release:

[Purnima Kumar, PhD, associate professor of periodontology at The Ohio State University and senior author of the study] used a DNA deep sequencing methodology to obtain an unprecedented in-depth view of these microbial communities in their natural setting.

When the scientists trained a machine to classify each assortment of microbes from under the gums according to ethnicity, a given bacterial community predicted an individual’s ethnicity with 62 percent accuracy. The classifier identified African Americans according to their microbial signature correctly 100 percent of the time.

The findings could help explain why people in some ethnic groups, especially African Americans and Latinos, are more susceptible than others to develop gum disease. The research also confirms that one type of dental treatment is not appropriate for all, and could contribute to a more personalized approach to care of the mouth.

The study was published in PLOS ONE.

Previously: “Mountain Dew mouth” rots teeth, costs taxpayersExploring the microbes that inhabit our bodies and Stanford researchers examine microbial communities of the mouth
Photo by manduhsaurus

Infectious Disease, Microbiology, Nutrition, Research, Stanford News

Joyride: Brief post-antibiotic sugar spike gives pathogens a lift

Joyride: Brief post-antibiotic sugar spike gives pathogens a lift

candy shackLet’s be clear: Antibiotics are a modern miracle. They’re also ancient history: During ancient times, moldy bread was traditionally used in Greece and Serbia to treat wounds and infections. Russian peasants used warm soil to cure infected wounds. Sumerian doctors gave patients beer soup mixed with turtle shells and snake skins. Babylonian doctors healed the eyes using a mixture of frog bile and sour milk. You get the drift.

At the same time, it’s not exactly breaking news that a course of antibiotics can wreak havoc with your gastrointestinal tract, where infamous intestinal pathogens such as salmonella and C. difficile can run amok.

“Antibiotics open the door for these pathogens to take hold,” according to Stanford microbiologist Justin Sonnenburg, PhD.

As I wrote in my press release about some exciting recent work by Sonnenburg, a healthy person’s large intestine is a menagerie teeming with miniature lifeforms:

The thousands of distinct bacterial strains that normally inhabit this challenging but nutrient-rich niche have adapted to it so well that we have difficulty living without them. They manufacture vitamins, provide critical training to our immune systems and even guide the development of our own tissues.

In return, our gut pays these industrious Oompa-Loompas salaries made of sugar – not common table sugar, but more exotic types, with names like fucose and sialic acid. Cells lining the intestine extrude long chains of such sugar varieties (these chains go by a familiar name: “mucus”) to feed its one-celled workhorses – as well as to keep them at arm’s length, so that they don’t get into the bloodstream and cause sepsis.

Everybody’s having fun until along come antibiotics and somebody gets hurt. The decimated gut-microbe ecosystem begins bouncing back within a few days, but  for as much as a month after a round of antibiotics we’re at heightened risk for infection by some bad, bad bugs.

In a new study, Sonnenburg and his colleagues snared some clues about how that works. They found that antibiotics’ inadvertent but inevitable gut-bugicide generates a transient surplus of sugars, including sialic acid and fucose, that have been liberated from gut mucus by good bugs who bit the dust before they got a chance to munch their lunch.

Salmonella lacks the equipment for carving sialic acid and fucose loose from the intestine’s extruded mucus, but it knows how to eat them. The bonanza, Sonnenburg’s team found, gives the pathogen the energy it needs to gain a toehold and launch a toxic takeover, leaving our gut in its hands.

Sonnenburg thinks there may be ways to slam the door that antibiotics open for unwanted intruders. For example, specialized probiotics with big appetites for fucose or sialic acid could be co-administered along with the antibiotics, cutting off the the nasty bugs’ stash until the nice ones repopulate the gut.

Sonnenburg’s work appears online in Nature.

Previously: The future of probiotics, Eat a germ, fight an allergy, What if gut-bacteria communities “remember” past antibiotic exposures? and Researchers manipulate microbes in gut
Photo by Lee Cannon

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

Did microbes mess with Typhoid Mary’s macrophages?

Did microbes mess with Typhoid Mary's macrophages?

macrophage with salmonella insideMary Mallon (a.k.a. “Typhoid Mary“) didn’t mean any harm to anybody. An Irish immigrant, she made her living for several years about a century ago by cooking for better-off families in the New York City area. Strangely, the people she cooked for kept on coming down with typhoid fever – but not Mary.

Mallon, alas, turned out to be a chronic asymptomatic carrier of Salmonella typhi, the bacterial strain that causes typhoid fever. Typhoid is a deadly disease that, while no longer a huge problem in the United States, infects tens of millions – and kills hundreds of thousands – of people around the world every year.

“She didn’t know she had it,” says Stanford microbiologist Denise Monack, PhD. “To all outward appearances, she was perfectly healthy.”

Salmonella strains, including one called S. typhimurium, also cause food poisoning in people and pets, taking an annual human toll of 150,000 globally. While S. typhi infects only humans, closely related S. typhimurium can infect lots of mammals.

Between 1 and 6 percent of people infected with S. typhi become chronic, asymptomatic typhoid fever carriers. Nobody has known why this happens, but it’s a serious public-health issue. To address this, Monack has developed an experimental mouse model that mimicks asymptomatic typhoid carriers. In a new study published in Cell Host & Microbe, she and her colleagues put that model to good effect, showing that Salmonella has a sophisticated way of messing with our immune systems. The bacteria set up house inside voracious attack cells called macrophages (from the Greek words for “big eater”). Macrophages, are known for their ability to engulf and digest pathogens and are called to the front lines of an immune assault against invading microbes. Ornery critters that they are, macrophages would seem like the last thing bacteria bent on long-term survival would want to meet.

But, as I wrote in my release about this study, a macrophage has two faces, depending on its biochemical environment:

“Early in the course of an infection,” [Monack] said, “inflammatory substances secreted by other immune cells stir macrophages into an antimicrobial frenzy. If you’re not a good pathogen, you’ll be wiped out after several days of causing symptoms.” But salmonella is one tough bug. And our bodies can’t tolerate lots of inflammation. So, after several days of inflammatory overdrive, the immune system starts switching to the secretion of anti-inflammatory factors. This shifts macrophages into a kinder, gentler mode. Thus defanged, anti-inflammatory macrophages are more suited to peaceful activities, such as wound healing, than to devouring microbes.

And, sure enough, Monack and her colleagues showed that salmonella germs have a way (still mysterious, but stay tuned) of taming macrophages, flipping an intercellular switch inside of these thug-like cells that not only expedites their champ-to-chump shift but induces them to pump out tons of glucose, the bug’s favorite food. What better place to hide than in the belly of the beast?
Previously: TB organism’s secret life revealed in a hail of systems-biology measurements
Photo by AJC1

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