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                                                                                                                                                                                                         SPECIALSECTION

                                                                          Body’s Hardworking Microbes                                                                               sequenced 500 relevant microbial genomes
                                                                                                                                                                                    out of a planned 3000.

                                                                          Get Some Overdue Respect                                                                                      Some of these microbes may play impor-
                                                                                                                                                                                    tant roles in metabolic processes. In 2004,
                                                                                                                                                                                    a team led by Jeffrey Gordon of Wash-
                                                                          HUMANS HAVE BEEN DOING BATTLE WITH                      This appreciation has dawned gradu-               ington University School of Medicine in
                                                                          bacteria since the 1800s, thwarting dis-            ally, as part of a growing recognition of             St. Louis, Missouri, found that germ-free
                                                                          ease with antibiotics, vaccines, and good           the key role microbes play in the world.              mice gained weight after they were supplied
                                                                          hygiene with mixed success. But in 2000,            Micro biologists sequencing DNA from                  with gut bacteria—evidence that these bac-
                                                                          Nobel laureate Joshua Lederberg called for          soil, seawater, and other environments have           teria helped the body harvest more energy
                                                                          an end to the “We good; they evil” thinking         discovered vast numbers of previously unde-           from digested foods. Later studies showed
                                                                          that has fueled our war against microbes.           tected species. Other genomics research               that both obese mice and obese people har-
                                                                          “We should think of each host and its para-         has brought to light incredible intimacies            bored fewer Bacteroidetes bacteria than their
                                                                          sites as a superorganism with the respective        between microbes and their hosts—such as              normal-weight counterparts.
                                                                          genomes yoked into a chimera of sorts,” he          a bacterium called Buchnera and the aphids                The microbiome is also proving critical in




                                                                                                                                                                                                                                                          Downloaded from www.sciencemag.org on February 19, 2011
                                                                          wrote in Science in 2000.                           inside which it lives. A study in 2000 found          many aspects of health. The immune system
                                                                              His comments were prescient. This past          that each organism has what the other lacks,          needs it to develop properly. What’s more, to
                                                                          decade has seen a shift in how we see the           creating a metabolic interdependency.                 protect themselves inside the body, commen-
                                                                          microbes and viruses in and on our bodies.              One of the first inklings that micro-             sal bacteria can interact with immune cell
                                                                          There is increasing acceptance that they are        biologists were missing out on the body’s             receptors or even induce the production of
                                                                          us, and for good reason. Nine in 10 of the          microbial world came in 1999, when David              certain immune system cells. One abundant
                                                                          cells in the body are microbial. In the gut         Relman of Stanford University in Palo Alto,           gut bacterium, Faecalibacterium prausnit-
                                                                          alone, as many as 1000 species bring to the         California, and colleagues found that previ-          zii, proved to have anti-inflammatory proper-
                                                                          body 100 times as many genes as our own             ous studies of bacteria cultured from human           ties, and its abundance seems to help protect
                                                                          DNA carries. A few microbes make us sick,           gums had seriously undercounted the diver-            against the recurrence of Crohn’s disease.
                                                                          but most are commensal and just call the            sity there. Turning to samples taken from the         Likewise, Sarkis Mazmanian of the Cali-
                                                                          human body home. Collectively, they are             gut and from stools, the researchers iden-            fornia Institute of Technology in Pasadena
                                                                          known as the human microbiome. Likewise,            tified 395 types of bacteria, two-thirds of            showed that the human symbiont Bacteroides
                                                                          some viruses take up residence in the body,         them new to science.                                  fragilis kept mice from getting colitis. And
                                                                          creating a virome whose influence on health              In 2006, Steven Gill of the University at         inserting bacteria isolated from healthy guts
                                                                          and disease is just beginning to be studied.        Buffalo in New York and colleagues did a              restored the microbial communities, curing
                                                                              Their genes and ours make up a meta-            metagenomics study of the gut, analyzing              chronic diarrhea in a patient infected with
                                                                          genome that keeps the body functioning. This        all the genes they could find in the 78 mil-           Clostridium difficile.
                                                                          past decade we’ve begun to see how micro-           lion bases sequenced. They found meta-                    Herbert Virgin of Washington University
                                                                          bial genes affect how much energy we absorb         bolic genes that complemented the human               School of Medicine finds a similar role for
                                                                          from our foods and how microbes and viruses         genome, including ones that break down                the virome. In mice, his team found that dor-
                                                                          help to prime the immune system. Viewing            dietary fiber, amino acids, or drugs, and oth-         mant herpesviruses revved up the immune
                                                                          the human and its microbial and viral com-          ers that produce methane or vitamins. This            system just enough to make the mice less sus-
                                                                          ponents as intimately intertwined has broad         and a more comprehensive survey in 2010               ceptible to certain bacterial infections.
                                                                          implications. As one immunologist put it,           by Jun Wang of BGI-Shenzhen in China and                  The ideas of a microbiome and a virome
                                                                          such a shift “is not dissimilar philosophically     colleagues provided support for the concept           didn’t even exist a decade ago. But now
                                                                          from the recognition that the Earth is not the      of the microbe-human superorganism, with              researchers have reason to hope they may
CREDIT: ADAPTED FROM L. DETHLEFSEN ET AL., NATURE 449 (18 OCTOBER 2007)




                                                                          center of the solar system.”                        a vast genetic repertoire. Now, large-scale           one day manipulate the body’s viral and
                                                                                                                              studies have surveyed the microflora in the            microbial inhabitants to improve health and
                                                                          Invisible partners. The roster of bacteria varies   gut, skin, mouth, nose, and female urogeni-           fight sickness.
                                                                          among body sites.                                   tal tract. The Human Microbiome Project has                                          –ELIZABETH PENNISI
                                                                                      Colon (195)
                                                                                                                                           Mouth (56)
                                                                                                                                                                  Esophagus (43)             Skin (48)
                                                                                                                                                                                                                    Stomach (25)
                                                                                                                                                                                                                                      Vagina (5)




                                                                                                                                            Firmicutes       Bacteroidetes         Actinobacteria          Proteobacteria          Other phyla



                                                                                                               www.sciencemag.org SCIENCE VOL 330 17 DECEMBER 2010                                                                                 1619
                                                                                                                                              Published by AAAS

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Body’s hardworking microbes get some overdue respect

  • 1. 2007 2008 2009 2010 2011 SPECIALSECTION Body’s Hardworking Microbes sequenced 500 relevant microbial genomes out of a planned 3000. Get Some Overdue Respect Some of these microbes may play impor- tant roles in metabolic processes. In 2004, a team led by Jeffrey Gordon of Wash- HUMANS HAVE BEEN DOING BATTLE WITH This appreciation has dawned gradu- ington University School of Medicine in bacteria since the 1800s, thwarting dis- ally, as part of a growing recognition of St. Louis, Missouri, found that germ-free ease with antibiotics, vaccines, and good the key role microbes play in the world. mice gained weight after they were supplied hygiene with mixed success. But in 2000, Micro biologists sequencing DNA from with gut bacteria—evidence that these bac- Nobel laureate Joshua Lederberg called for soil, seawater, and other environments have teria helped the body harvest more energy an end to the “We good; they evil” thinking discovered vast numbers of previously unde- from digested foods. Later studies showed that has fueled our war against microbes. tected species. Other genomics research that both obese mice and obese people har- “We should think of each host and its para- has brought to light incredible intimacies bored fewer Bacteroidetes bacteria than their sites as a superorganism with the respective between microbes and their hosts—such as normal-weight counterparts. genomes yoked into a chimera of sorts,” he a bacterium called Buchnera and the aphids The microbiome is also proving critical in Downloaded from www.sciencemag.org on February 19, 2011 wrote in Science in 2000. inside which it lives. A study in 2000 found many aspects of health. The immune system His comments were prescient. This past that each organism has what the other lacks, needs it to develop properly. What’s more, to decade has seen a shift in how we see the creating a metabolic interdependency. protect themselves inside the body, commen- microbes and viruses in and on our bodies. One of the first inklings that micro- sal bacteria can interact with immune cell There is increasing acceptance that they are biologists were missing out on the body’s receptors or even induce the production of us, and for good reason. Nine in 10 of the microbial world came in 1999, when David certain immune system cells. One abundant cells in the body are microbial. In the gut Relman of Stanford University in Palo Alto, gut bacterium, Faecalibacterium prausnit- alone, as many as 1000 species bring to the California, and colleagues found that previ- zii, proved to have anti-inflammatory proper- body 100 times as many genes as our own ous studies of bacteria cultured from human ties, and its abundance seems to help protect DNA carries. A few microbes make us sick, gums had seriously undercounted the diver- against the recurrence of Crohn’s disease. but most are commensal and just call the sity there. Turning to samples taken from the Likewise, Sarkis Mazmanian of the Cali- human body home. Collectively, they are gut and from stools, the researchers iden- fornia Institute of Technology in Pasadena known as the human microbiome. Likewise, tified 395 types of bacteria, two-thirds of showed that the human symbiont Bacteroides some viruses take up residence in the body, them new to science. fragilis kept mice from getting colitis. And creating a virome whose influence on health In 2006, Steven Gill of the University at inserting bacteria isolated from healthy guts and disease is just beginning to be studied. Buffalo in New York and colleagues did a restored the microbial communities, curing Their genes and ours make up a meta- metagenomics study of the gut, analyzing chronic diarrhea in a patient infected with genome that keeps the body functioning. This all the genes they could find in the 78 mil- Clostridium difficile. past decade we’ve begun to see how micro- lion bases sequenced. They found meta- Herbert Virgin of Washington University bial genes affect how much energy we absorb bolic genes that complemented the human School of Medicine finds a similar role for from our foods and how microbes and viruses genome, including ones that break down the virome. In mice, his team found that dor- help to prime the immune system. Viewing dietary fiber, amino acids, or drugs, and oth- mant herpesviruses revved up the immune the human and its microbial and viral com- ers that produce methane or vitamins. This system just enough to make the mice less sus- ponents as intimately intertwined has broad and a more comprehensive survey in 2010 ceptible to certain bacterial infections. implications. As one immunologist put it, by Jun Wang of BGI-Shenzhen in China and The ideas of a microbiome and a virome such a shift “is not dissimilar philosophically colleagues provided support for the concept didn’t even exist a decade ago. But now from the recognition that the Earth is not the of the microbe-human superorganism, with researchers have reason to hope they may CREDIT: ADAPTED FROM L. DETHLEFSEN ET AL., NATURE 449 (18 OCTOBER 2007) center of the solar system.” a vast genetic repertoire. Now, large-scale one day manipulate the body’s viral and studies have surveyed the microflora in the microbial inhabitants to improve health and Invisible partners. The roster of bacteria varies gut, skin, mouth, nose, and female urogeni- fight sickness. among body sites. tal tract. The Human Microbiome Project has –ELIZABETH PENNISI Colon (195) Mouth (56) Esophagus (43) Skin (48) Stomach (25) Vagina (5) Firmicutes Bacteroidetes Actinobacteria Proteobacteria Other phyla www.sciencemag.org SCIENCE VOL 330 17 DECEMBER 2010 1619 Published by AAAS