The Human Microbiome: Your Own Personal Ecosystem
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Developed by the Federation of American Societies for Experimental Biology (FASEB) to educate the general public about the benefits of fundamental biomedical research. INSIDEthis issue The Human Microbiome: Your Own Personal Ecosystem Animalcules 1 Germs 1 Cultural Variety 2 A Microbial Menagerie 3 A Blank Canvas 4 Stomach Bug 5 From Battlefield to Ecosystem 5 The Great Plate Count Anomaly and its Resolution 7 Unexpected Variety 8 Weighty Effects 9 The Human Microbiome Project 10 A Microbiome Success Story 12 A New Frontier 12 Acknowledgments The Human Microbiome: Your Own Personal Ecosystem Author, Jacqueline Jaeger Houtman, PhD Scientific Advisor, Sarah K. Highlander, PhD, J. Craig Venter Institute Scientific Reviewer, Karen Guillemin, PhD, University of Oregon BREAKTHROUGHS IN BIOSCIENCE COMMITTEE Paula H. Stern, PhD, Chair, Northwestern University Feinberg School of Medicine Aditi Bhargava, PhD, University of California San Francisco David L. Brautigan, PhD, University of Virginia School of Medicine Blanche Capel, PhD, Duke University Medical Center Rao L. Divi, PhD, National Cancer Institute, National Institutes of Health Marnie Halpern, PhD, Carnegie Institution for Science Tony E. Hugli, PhD, Torrey Pines Institute for Molecular Studies Edward R. B. McCabe, MD, PhD, March of Dimes Foundation Loraine Oman-Ganes, MD, FRCP(C), CCMG, FACMG, Sun Life Financial Sharma S. Prabhakar, MD, MBA, FACP, Texas Tech University Health Sciences Center COVER: In 1964 René Dubos wrote: “Our recent studies have revealed that there exists in normal animals an R. Brooks Robey, MD, FASN, FAHA, White River Junction VA abundant and characteristic microflora, not only in the Medical Center and Geisel School of Medicine at Dartmouth large intestine, but also in all the other parts of the digestive tract, including the mouth, the stomach and Scott I. Simon, PhD, University of California Davis the small intestine. These microorganisms should not be regarded merely as contaminants. Rather, they become so intimately associated with the various digestive organs BREAKTHROUGHS IN BIOSCIENCE that they form with them a well-defined ecosystem of PRODUCTION STAFF which each component is influenced by the others, and by the environmental conditions.” Dubos’s observations Managing Editor, Anne M. Deschamps, PhD, Senior Science as well as discoveries from other scientific disciplines Policy Analyst, FASEB Office of Public Affairs and advances in scientific technologies have allowed scientists to begin exploring the effects of our personal Production Staff, Lawrence Green, Communications Manager, ecosystem on health and disease. FASEB Office of Public Affairs Cover illustration: © Michael Linkinhoker, Link Studio, LLC The Human Microbiome: ECOSYSTEMYour Own Personal Ecosystem We are not alone. For each of the ten than-perfect oral hygiene, where he at the time infectious diseases were trillion human cells in our bodies, found “an unbelievably great company thought to be caused by poisonous there are ten microbial cells living in of living animalcules, a-swimming vapors, the influence of heavenly and on us. Our own cells encode about more nimbly than any I had ever seen bodies, and bad smells. 20,000 genes, but the sum total of up to this time.” He even described genes in our body is close to a billion. what seems to have been the intestinal Germs The vast majority of these are the pathogen Giardia lamblia from his Two centuries later, in France, Louis genes carried by microbes. own feces during a bout of diarrhea. Pasteur studied the organisms that For more than three hundred Leeuwenhoek reported in great depth ferment wine and beer (beneficial years, scientists have observed, on his findings with a sense of wonder organisms, to be sure). He determined that the “wrong” organisms could spoil identified, and implicated individual and curiosity. He made no connection the beverage. This led him to the idea microorganisms in specific diseases. between microbes and disease, since More recently, with a convergence that specific microbes could cause of scientific disciplines, an explosion diseases in humans. The germ theory of in technical capabilities and disease was further expanded by Robert revolutionary new ways of thinking, Koch, who was responsible for several we are exploring the organisms technical and conceptual innovations with which we share our bodies. that would make the modern science of The effects of these organisms—our microbiology possible. microbiome—on our health are only At the time, microbiologists grew just being recognized. bacteria in liquids such as meat broths. If more than one kind of organism Animalcules grew in the liquid, it was impossible The first person to observe to separate them. Koch, however, microorganisms associated with developed a way to obtain pure the human body was Antonie van cultures. At first, he used the surface Leeuwenhoek, a Dutch merchant in of sliced potatoes. Each of the small the seventeenth century. Although raised bumps that grew on the potato he did not invent the microscope, Figure 1 – Animalcules: surface was a colony of bacteria he was the first to construct devices Leeuwenhoek had boundless curiosity derived from a single organism. Koch with enough magnification and clarity and “whenever I found out anything began looking for a more suitable solid to see life forms as tiny as bacteria. remarkable, I have thought it my on which to grow bacteria. Initially, duty to put down my discovery on He described and drew pictures of paper, so that all ingenious people the best solution seemed to be gelatin, what he saw, including organisms might be informed thereof.” He used an animal protein, but it was not from the cleft in between his teeth his microscope to look at bacteria, without problems. For one thing, many and gum, where he observed “many protozoans, nematodes, sperm cells, bacteria consume gelatin, and those very little living animalcules, very blood cells, muscle fibers, yeast, algae, that caused disease in humans grew fleas, bees, aphids, diatoms, mineral prettily a-moving.” Not content with crystals, and fossils. best at human body temperature—the looking at the stuff in his own mouth, Image credit: © Ann Ronan Picture point at which gelatin melts. Even on he searched out family members and Library/Heritage Images/Imagestate very warm days, gelatin would turn neighbors, especially those with less- from solid to liquid. 1 Figure 2 – Robert Koch: Often Figure 3 – Angelina and Walther Hesse: Angelina helped Walther in the referred to as the founder of modern Koch laboratory as a technician. She also illustrated many of his publications. The bacteriology, Robert Koch developed agar she used in her jellies became the basis for the agar plates used in modern new ways of studying bacteria and microbiology laboratories. infectious diseases. He was awarded Image credit: National Library of Medicine the 1905 Nobel Prize in Physiology or Medicine “for his investigations and discoveries in relation to tuberculosis.” Important as these technical Christian Gram introduced a stain Image credit: Science Photo Library innovations were, Koch’s conceptual that made bacteria easier to see under contribution was perhaps the most the microscope. It also turned some Walther Hesse, a scientist in Koch’s influential. Koch’s postulates were bacteria purple and some pink. This first lab, told his wife, Angelina, about the formulated to determine the microbial differential stain, based on structural gelatin problem. Angelina knew that cause of infectious disease. Using differences of the cell wall, is still used to her fruit jellies stayed solid throughout these rules, scientists could be sure the summer heat because she used that the organism in question was the agar-agar. First used in Japan in the perpetrator of pathogenesis and not 1600s, agar-agar (or agar) is derived just an innocent bystander. from seaweed and is sometimes used In 1876, Koch was the first to today as a vegetarian substitute for associate a particular disease, anthrax, gelatin. Unlike the protein gelatin, with a specific organism, Bacillus agar is a polysaccharide that is not anthracis. He also discovered the generally used by bacteria as food, microbial causes of tuberculosis and and it stays solid at temperatures used cholera. In the next thirty years, the to grow the cultures. bacteria that cause more than a dozen Staples in the modern microbiology diseases, from gonorrhea to dysentery lab, agar and the Petri dish (invented to whooping cough, were identified. Figure 4 – Petri dish with agar by Julius Petri in the Koch lab) made For a century, Koch’s postulates were and bacterial colonies: Using materials the gold standard for determining the and techniques first developed in Robert it easy to isolate and grow pure Koch’s lab, isolated colonies can be cause of infectious disease. cultures of bacteria descended from produced by diluting a culture in liquid a single cell. By diluting a liquid medium or on the plate itself until the culture, and then spreading it on Cultural Variety sample is dilute enough to separate individual cells, each of which grows agar in Petri dishes, bacteriologists At first, scientists could only tell one into a colony. could count the colonies and calculate kind of bacterium from another by Image credit: Alina Cardiae how many bacteria were in the their shape and ability to move around. Photography/Shutterstock original culture. In 1884, Danish bacteriologist Hans Breakthroughs in Bioscience 2 A GRAM-POSITIVE BACTERIA B GRAM-NEGATIVE BACTERIA KOCH’S POSTULATES (i.e., Staphylococcus) (i.e., Escherichia coli) 1. The microorganism must be present in all cases of the disease. 2. The disease-causing organism (pathogen) can be isolated from the diseased host and grown in pure culture. 3. The pathogen from the pure culture must cause the Cell wall – peptidoglycan layer (retains crystal violet dye) disease when inoculated into a healthy, susceptible Cell wall Outer plasma laboratory animal. (crystal violet membrane dye is washed Peptidoglycan 4. The pathogen must be away) layer re-isolated from the new Inner plasma membrane host and shown to be (Lipid bilayer) the same as the originally inoculated organism.