The document discusses how views of microbes have shifted over the past decade from seeing them as "evil" to recognizing that they play a key role in human health as part of the human microbiome. Research has found that microbes make up most of the cells in the human body and contribute significantly to metabolic processes. Studies sequencing microbial genomes and analyzing microbial communities in places like the gut have revealed far more microbial diversity than previously known and shown how microbes interact closely with human hosts. The microbiome is now understood to influence important functions like immune development and energy extraction from food.

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
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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
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