Intestinal section from a gnotobiotic mouse model inoculated with selected human bacterial species. Blue=Bacteroides WH2, green=Bacteroides thetaiotamicron, pink=Bacteroides vulgatus, yellow=Collinsella aerofaciens, red=Ruminococcus torques. Credit: Yuko Hasegawa/MBL Woods Hole.
landmark publication this week of a “map” of the bacterial make-up of
healthy humans has deep roots in an unexpected place: the ocean.
communities that live on and in the human body, known collectively as
the microbiome, are thought to have a critical role in human health and
disease. Five years ago, the National Institutes of Health launched the
ambitious Human Microbiome Project (HMP) to define the boundaries of
bacterial variation found in 242 healthy human beings.
order to understand what sick is, it’s helpful to define the healthy
microbiome first,” says MBL scientist Susan M. Huse, lead author of one
of the HMP reports published this week.
project’s 200 scientists from 80 institutions, including Huse and
Mitchell Sogin from the MBL, faced the daunting task of making sense of
more than 5,000 samples of human and bacterial DNA and 3.5 terabases of
solution? The HMP adopted several, state-of-the-art genetic sequencing
and analysis methods, many of which were originally developed by the MBL
for the International Census of Marine Microbes—a massive, ten-year
project that yielded the first inventory of microbial diversity in the
perhaps not surprisingly, the HMP discovered that microbial
distributions in the human body are not so different from those in ocean
in the human gut, mouth, or vagina, the Pacific Ocean or the Sargasso
Sea, microbial communities contain a few highly abundant bacterial types
plus many, many more low-abundance types (the so-called “rare
biosphere,” a phenomenon first discovered in ocean samples by Sogin and
his MBL colleagues).
more closely we look, the more bacterial diversity we find,” Huse says.
“We can’t even name all these kinds of bacteria we are discovering in
human and environmental habitats. It’s like trying to name all the
stars.” HMP researchers concluded that an estimated 10,000 bacterial
species occupy the human microbiome.
HMP also confirmed that in people, like in the ocean, which bacteria
are abundant and which are rare varies from site to site. The common
bacterium Bacteroides, for instance, can comprise nearly 100% of the
microbes in one person’s gut, yet be barely present in another’s.
this means is, there is not just one way to be healthy, ” says Huse.
“There doesn’t have to be one or two ‘just right’ gut communities, but
rather a range of ‘just fine’ communities.”
key finding of the HMP is that nearly everyone carries
pathogens—microbes known to cause illness. In healthy individuals,
however, pathogens cause no disease; they simply co-exist with the rest
of the rare and abundant microbes in the person’s microbiome.
Researchers now must figure out why some pathogens turn deadly and under
what conditions, likely revising current concepts of how microorganisms
really important to understand how and why these rare organisms
‘swing,’” Huse says. “And one of the problems we have is people take
antibiotics, which really change the microbiome. Antibiotics can kill
the abundant bacteria, which then allows the rare bacteria to flourish
in a gut environment full of food. If the rare bacteria include a
pathogen, then you can get sick.”
HMP employed two major strategies to characterize the microbes in 18
different sites in the mouth, nose, skin, vagina, and stool of the
volunteers. The first strategy told them “who” was there. Called 16s
rRNA tag sequencing, the MBL first adapted this method for
“next-generation” sequencing in the mid-2000s, in order to identify
which microbes were present in ocean samples and their relative
abundances. (Next-generation sequencing produces large volumes of
sequencing data much more inexpensively than traditional methods.) The
second strategy the HMP adopted, called shotgun sequencing, was employed
to find out what functions the microbes might be performing.
we have a list of ‘who’ is in the human microbiome, and another list of
what they are doing. Part of the task ahead is to tie together which
organisms are doing what functions,” Huse says.
how people are the same, despite the variations in their microbiomes,
is another significant challenge for future investigation. “At some
level there have to be similarities, because we are all eating and
digesting and so forth,” Huse says. “Perhaps the different aspects of
digestion and immune system interaction can be performed by a variety of
different assemblages of bacteria.”