A REPORT FROM THE AMERICAN ACADEMY OF MICROBIOLOGY HUMAN MICROBIOME ABOUT ASM FAQs The American Academy of Microbiology is the honorific branch of the American Society for Microbiology, a non-profit scientific society with almost 40,000 members. Fellows of the AAM have been elected by their peers in recognition of their outstanding contributions to the field of microbiology. Through its colloquium program, the AAM draws on the expertise STEERING COMMITTEE: PARTICIPANTS: of these fellows to address critical issues in microbiology. Lita Proctor, Ph.D. Brett Finlay, Ph.D. National Human Genome The University of British Columbia Research Institute/NIH FAQ reports are based on the Wendy Garrett, M.D., Ph.D. deliberations of 15-20 expert scientists Jacques Ravel, Ph.D. Harvard University who gather for a day to develop University of Maryland science-based answers to questions School of Medicine Gary Huffnagle, Ph.D. the public might have about topics in University of Michigan microbiology. The reports are reviewed Peter Turnbaugh, Ph.D. by all participants, and by outside experts, Harvard University Curtis Huttenhower, Ph.D. and every effort is made to ensure that Harvard University the information is accurate and complete. Janet Jansson, Ph.D. However, the report is not intended to ASM STAFF Lawrence Berkeley National Lab advocate any particular position or action, nor to replace the advice of an individual’s Leah Gibbons Rob Knight, Ph.D. health care provider. Colloquium and Public University of Colorado at Boulder Outreach Program Assistant The AAM does not offer medical advice Sarkis Mazmanian, Ph.D. and encourages consumers to be Shannon E. Greene, Ph.D. California Institute of Technology Colloquium Fellow educated and informed when making David A. Mills, Ph.D. medical decisions. Ann Reid University of California, Davis Director Contents of the report may be distributed Dave Relman, M.D. further so long as the authorship of the Stanford University AAM is acknowledged and this disclaimer is included. Vincent Young, M.D., Ph.D. University of Michigan Copyright © 2013 American Academy of Microbiology 1752 N Street, NW Washington, DC 20036 www.asm.org Written by Ann Reid and Shannon Greene 1) What is the human microbiome? If you think back to your high school biology class, you probably remember learning about cells. You learned that the human body is made up of many different kinds of cells — skin cells, muscle cells, neurons, and blood cells, for example. You might even remember learning that each of these different kinds of cells develops and functions in accordance with the directions encoded by a single set of genes shared by all human cells and that the full set of these human genes is called the human genome. FAQ: MICROBIOME 1 Wait a minute, what’s a microbe? The term “microbe” is used to describe organisms that are too small to be seen with the naked eye. Microbes include bacteria, archaea, fungi, protists, and viruses. Bacteria and archaea are single-celled organisms that do not enclose their genetic material in a nucleus. Although similar in appearance, at the genetic level bacteria and archaea are only very distantly related. Together, these two life forms represent a huge proportion of the diversity of life on Earth, each constituting a major branch, or domain, of the tree of life. The third major branch, the Eukarya, includes all the plants and animals you can see (including humans). There are also many microbes on the eukaryotic branch of the tree of life, including some fungi (like yeast), some algae, amoebas, slime molds and protozoa. Finally, viruses are also considered microbes. Because viruses can only reproduce by infecting cells and hijacking the cell’s own machinery to make new viruses, there is debate as to whether they can be considered alive and they are not included in the universal tree of life. Undoubtedly, though, viruses play many important, even essential, roles in biological systems, so they What you almost certainly did not hear about was that must be taken into account as important participants the human body also contains trillions of cells that are in microbial communities. not human, but microbial, each of which has its own unique complement of genes. Together, these microbes constitute the human microbiome and scientists are now finding that they play an important role in human BACTERIA health. If you need a little refresher course on the mitochondrio definition of microbes, please take a look at the box ARCHAEA Rhodoc terium Escherichia entitled “Wait a minute! What’s a microbe?” er s t Planctomyces chloroplasDesulfovibrio lavobac Thermococcus Synecho yclu F n Methan grobacterium s lexibac bacterium A F ax ChlamydiaGloeobactecoc t Methanothermus marine low temp chaeoglobus The bottom line is that the human body hosts a cus Ar Halofer Chlorobium r o- Thermoplasma Methanopyrus Methanococcu Methanospirillum Leptonem huge number of microbes of many different kinds. a marine Gp 1 low temp Clostridium Gp 2 lowGp 1 temp low temp Bacillus pSL 22pSL 12 These microbes play a role in many fundamental life r Gp 3 low Sulfolobus Helicobacteriumthrobacte Pyrodictium temp Ar pOPS19 s Thermoproteus processes. The collection of microbes that constitute root pSL 50 Thermu pJP 27pJP 78 ThermatogapOPS66 the microbiome is not random; the human microbiome Aquifex EM17 is made up of a particular set of microbes that Humans are here Coprinus Homo complement each other and the human host. Systematic Corn is here Zea Cryptomonas study of the human microbiome is a very young a Achly a science and scientists are just beginning to address the Costaria Giardi Porphyr questions of what constitutes a normal microbiome, abesia a amecium r B Physarium T Pa richomonas a how the microbiome changes over time, and how the yostelium i n Tr e Euglen Enc l Dict g ypanosoma e V composition and activity of the microbiome affect health ephalitozoo a airimorpha N Enantomeoba EUCARYA a and disease. What is already clear is that the effect of the microbiome on its human host is profound and n multifaceted. Indeed, it is reasonable to characterize the microbiome as a newly recognized organ, with a great range of metabolic activities. Norman R. Pace, A Molecular View of Microbial Diversity and the Biosphere. Science 276, 734 (1997) 2 A REPORT FROM THE AMERICAN ACADEMY OF MICROBIOLOGY Definitions: The term “human microbiome” is so new that there n Microbiome: This term has two definitions, one is not yet a fully agreed upon definition. But names genetic and one ecological. matter. It’s worth exploring how scientists talk about the microbial communities associated with the human body, n Definition 1: Just as the entire collection of because when a new field of study is first emerging, human genes is called the human genome, definitions are important. They ensure that everyone is this definition of microbiome means the talking about the same thing. entire collection of genes found in all of the microbes associated with a particular host. A Humans are not the only organisms that have a closely broader term, “metagenome” means the entire associated microbial community. In fact, there are collection of microbial genes found in a particular microbial communities everywhere — in the soil, in the environment. A “metagenome” may or may not ocean, in every building and water pipe, and on every be host-associated — metagenomes have been plant and animal. So the terms below can be used to generated for sea water, showerheads, and hot describe microbial communities wherever they are found. springs, among many other environments. n Microbiota: all the microorganisms that live in a n Definition 2: Ecologists use the term “biome” particular environment, for example, the human body. to describe the collection of plants and animals The organisms living on humans were once called that live in a particular environment. Thus the “microflora” but this term is now considered there are various terrestrial and aquatic biomes incorrect and misleading, since it implies that humans (temperate grasslands, or tropical coral reefs, are colonized with tiny plants. The organisms that for example) that are characterized by similar constitute the human microbiota are not plants; they climatic conditions and collections of organisms. are microbes of various kinds. When microbiome is used in this sense, it refers to the ecosystem made up of microbes within and on the human body — that is, the collection of microbes that live in the human ”habitat.” FAQ: MICROBIOME 3 2) Where does our microbiome come from? The microbial world may be largely invisible Billions of years before multicellular organisms emerged, microbes had seemingly occupied every to the human eye, but it is vast almost possible ecological niche. The emergence of multicellular beyond imagination. There are hundreds organisms created an entirely new set of habitats — in and on all those animals and plants. The kinds of partnerships of thousands of different kinds of bacteria between animals and plants and their microbes are just alone (leaving aside for the moment the other beginning to be explored, but the important thing to recognize is that these associations are not random. Each kinds of microbes: archaea, viruses, fungi, organism has evolved to have intimate associations with and protists), living in every conceivable particular kinds of microbes — perhaps not exactly the same species in every case, but with characteristic types. environment including deep under the seabed, Humans are no exception; of the hundreds of thousands high in the clouds, in the near boiling hot of kinds of microbes on Earth, only about 1,000 have been found associated with humans. springs of Yellowstone National Park, and in highly acidic drainage from old mines. So there are hundreds of thousands of different kinds of microbes in the world, and several hundred different 4 A REPORT FROM THE AMERICAN ACADEMY OF MICROBIOLOGY kinds are generally found in the average human microbiome.