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  • 'We are 90 percent bacteria'

    Researchers trace a wilderness of viruses, fungi and bacteria in hospital
  • CHICAGO — Biologist Daniel Smith crouched in an empty patient room at the new University of Chicago hospital and dragged a white cotton swab across the gleaming tile.
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    Smith studied the dust-smudged tip before breaking it off into a plastic tube labeled "floor."
    "A good sample for us," said Smith, securing the tiny vial in a box chilled by dry ice. "Although you can't see them, there are literally billions of (bacteria) cells on these surfaces."
    Like scientists who began classifying the world's plants and animals centuries ago, Smith and his colleagues at Argonne National Laboratory are embarking on a similar exploration, only in the micro realm.
    Over the next year, they plan to trace the ebb and flow of the hospital's microbiome — a vast wilderness of viruses, fungi and, perhaps most importantly, bacteria — to better understand how it may affect human health in an environment where about 100,000 people die nationally every year from acquired infections.
    The effort, known as the Hospital Microbiome Project, follows similar surveys of bacterial communities in the human body, where the single-cell organisms outnumber human cells by 10 to 1. It is also part of a growing area of microbial research, bolstered by recent advances in molecular biology and computer science, that has led some scientists to wonder whether the strongest forces shaping human life may not, in fact, be human.
    Or, as California Institute of Technology microbiologist Sarkis Mazmanian likes to tell people, "We are 90 percent bacteria."
    "If you think about the way we function on a cellular level, all the activities that confer health and disease are not just encoded in our own DNA. Some of those are encoded in our bacterial DNA," Mazmanian said.
    "So how much of the way we function, even maybe the way we think, is from our own doing? How much of us is really human?"
    Since at least the late 17th century, when Dutch scientist Anton van Leeuwenhoek scraped scum from his teeth and observed tiny "animalcules" in the plaque samples beneath his microscope, humans have had an inkling of the microbial world in and around them.
    But that understanding has been overly simplistic, according to Jack Gilbert, a microbial ecologist at Argonne and head of the laboratory's microbiome endeavors.
    Human beings are blanketed by microbes from the moment they emerge into the world. A vast majority of the human microbiome, comprising 10 trillion to 100 trillion cells, thousands of species and at least 8 million unique genes, is not only harmless, but vital to life. By breaking down food, bacteria produce essential vitamins, anti-inflammatories and compounds that fuel the human metabolism.
    Yet the overriding premise has been that microorganisms are the ecological foes of humans, meant only to be destroyed.
    "We equate bacteria with small insects," said Gilbert during a recent interview on Argonne's sprawling campus near Lemont. The use "of the word 'bug' for bacteria, comes from this fear of these little creepy, crawly insects crawling all over everything," he said.
    The arsenal of microbial warfare — antibiotics, vaccines, and simple soap and water — has saved millions of lives, and Gilbert and his ilk do not recommend the retirement of such vital weapons.
    Instead, their mission is more nuanced: By sifting through microbe genomes, they hope to sort out the complex interactions that make some landscapes beneficial while turning others more destructive.
    The work, in part, builds on the Human Microbiome Project, which began in 2007 to sequence the microbial DNA in healthy humans and those suffering from a variety of medical conditions like gastroesophageal reflux disease and irritable bowel syndrome.
    The project, funded by the National Institutes of Health, concluded that certain microbiomes appear to be associated with or even precede specific diseases.
    "It isn't just the human on this side and microbes on the other side," said NIH project coordinator Lita Proctor. "It helped us think about microbes not as single entities, not as a single germ or pathogen, but as whole communities interacting with each other and their environment."
    Scientists are still defining that relationship, but recent studies have shown that changes in the microbiome may impact health in varied ways.
    To underscore that point, Dr. Alexander Khoruts often mentions a patient who contracted a persistent Clostridium difficile infection in 2009. The rod-shaped bacteria typically take up residence in the colon after normal bacteria have been wiped out by antibiotics. Left unchecked, the bacteria can cause diarrhea, inflammation of the colon and, in about 14,000 cases a year, death.
    By the time the patient came to him, Khoruts said, she had already lost more than 60 pounds and had to use a wheelchair.
    "She was, essentially, slowly dying," said Khoruts, a gastroenterologist at the University of Minnesota Medical Center, Fairview.
    With dwindling options, Khoruts recommended that the patient's husband provide his wife with a sample of bacteria from his colon.
    Shortly after the procedure, called a fecal transplant, testing indicated the patient had a flourishing composition of bacterial species in her colon. The infection was gone.
    In the field of microbiome research, the fecal transplant has become an unlikely darling — elegantly demonstrating how gut microbes influence health. But intriguing preliminary results have popped up across the scientific spectrum.
    For example, when scientists gave mice gut microbes from obese mice, the recipient mice packed on more fat. In other studies, mice given a molecule produced by the gut bacterium Bacteroides fragilis were protected against diseases like multiple sclerosis and inflammatory bowel disease. And, in a 2011 paper, scientists found that microbe-free mice engaged in riskier behavior than their healthy, microbiome-possessing counterparts did.
    "If we can understand (the microbiome)," said Mazmanian, who is investigating how microbes may bolster the immune system. "I think we can really get a foothold on understanding many different diseases."
    Experts caution that microbiome research and the use of probiotics — or live bacteria believed to be beneficial to humans — are still very much in their infancy.
    Despite claims attached to varying brands of yogurt, scientists are still trying to make sense of how, exactly, various bacteria may function when ingested. And though fecal transplants have appeared to work for some infections, certain live bacteria may actually harm patients who have weakened immune systems.
    "It's still super early days," Proctor said. "We're just really at the census level. What we really want to know from the biomedical perspective is, what are the microbes doing? And when do you have a good microbiome? And when do you have one that's gone south? We're still struggling with trying to figure out even how to measure" that.
    More and more scientists, however, are now seeking answers to those questions.
    From his spare office at Argonne, Gilbert helms the Earth, Home and newly launched Hospital microbiome projects. He also spearheads other microbial efforts, exploring whether bacterial sprays and other products can boost crops or help soldiers mask their presence from mosquitoes.
    "This is the microbial century," said Gilbert, who launched the Earth Microbiome Project in July 2010.
    The thrust of the endeavor, which colleagues have warmly deemed "a huge, crazy project," is to identify and determine the function of all the Earth's microbes, "for the benefit of the planet and mankind."
    By understanding the microorganisms in various environments, Gilbert, 35, hopes to understand where the microbes living on humans come from.
    "You can't, literally, just isolate humans and say, 'I want to know about human health,'" Gilbert said. "You've got to look at the environment that humans interact with."
    Many people, however, spend more time indoors than outdoors. So, Gilbert also started the Home Microbiome Study, peering into microbial outposts in houses and apartments, and, most recently, the Hospital Microbiome Project.
    Over the next 13 months, Daniel Smith and others will collect about 15,000 samples from the top two floors of the University of Chicago's new hospital, the Center for Care and Discovery, slated to open in February. They will swipe sterile swabs across floors, counters, faucets and patients and staff and collect hundreds of air filters.
    The microbial DNA will be taken to Gilbert's lab at Argonne, where scientists will run it through high-powered sequencing machines that are able to read hundreds of billions of base pairs — the building blocks of DNA — every couple of days. Just five years ago, it would have taken more than a year to do the same amount of work, according to Gilbert.
    Preliminary runs have shown that similar types of surfaces harbor similar bacteria and that bacteria living in the hospital regularly hop onto the shoes of visitors, who then track them outside.
    Whether that is good, bad or even relevant to human health remains to be seen. But by building on that knowledge in the coming months and years, Gilbert would like to be able to provide hospitals with information that can be used to prevent certain infections, and ultimately, related deaths.
    "Our hope," Gilbert said, "is that this data will be able to tell us how health care-associated pathogens affect people in these buildings and how transient they are, how persistent they are, and what we can do to stop them."
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