Microb Ecol (2013) 65:916–919
DOI 10.1007/s00248-013-0227-y
MINIREVIEWS
Microbiomes
Karen E. Nelson
Received: 14 January 2013 / Accepted: 27 March 2013 / Published online: 23 April 2013
# Springer Science+Business Media New York 2013
Abstract During the past decade, there has been an explo-
sion in the quantity of sequencing data that has come out of
the studies of microbiomes. This has resulted primarily from
new technological developments to interrogating any envi-
ronment of choice. Additional downstream applications to
interrogating these datasets include “omics” studies such as
transcriptomics and proteomics, all leading to a deeper
understanding of microbial diversity and the multitude of
species that remain uncultured. Metagenomic studies are
now being performed routinely on a wide range of environ-
ments including soils, oceans, air, plants, and various animal
species. They are being used to identify novel microbial
species, new pathways, and to elucidate the roles of viruses
and phage in the environment. In this review, we get a
perspective on where the science is headed and what we
expect to learn as additional studies unfold.
Introduction
The initial diversity surveys of microbial communities
focused primarily on the use of the 16S rRNA gene
sequence—a conserved phylogenetic marker thought to
be reliably amplified by a range of “universal primers”
[18, 19]. Almost three million 16S rRNA gene sequen-
ces are currently available (http://rdp.cme.msu.edu/) and
represent the interrogation and analysis of many differ-
ent environments on our planet. Though some of the 16S
rRNA gene sequences represent those derived from cultivated
species, the majority have been derived from uncultivated
species and generated during diversity surveys. Although
16S rRNA gene diversity surveys continue to be performed,
K. E. Nelson (*)
J. Craig Venter Institute (JCVI), 9704 Medical Center Drive,
Rockville, MD 20850, USA
e-mail: karennel@gmail.com
they have been replaced to some extent by larger data-driven
metagenomics studies as a result of the coming together of a
number of improved technologies coupled with a significant
reduction of costs.
Proof of principle was demonstrated in 2004 [28], when
Venter and colleagues used metagenomics with the Sanger
platform to sequence seawater samples collected from the
Sargasso Sea. In this study, they generated 1.045 billion bp
of non-redundant sequences that were thought to have come
from 1,800 species. They also described more than 1.2
million previously unknown genes [28]. This study essen-
tially launched the field of metagenomics whereby we can
now sequence the microbial communities that are present in
any environment en masse. From the studies of the oceans
[23, 24, 28, 31–33], metagenomics surveys have evolved to
include numerous animal species [2, 22, 26], soils [5, 6], air,
and the human body [1, 11, 12].
Ruminant studies were among the earliest metagenomic
studies with population studies of microbe changes under
different diets being examined by White and colleagues [2,
8]. Several other animal species have since been subject to
metagenomic sequencing—primarily with a goal to under-
stand the populations associated with health or with the
metabolism of food in the gastrointestinal tract and how
these populations vary during disease or under different
diets respectively. Ruminants have also been examined for
novel enzymatic activities associated with the metabolism of
cellulose material [21] and urea [4]. The animal species that
have been interrogated range from food animals to exotic
species. See for example Pope and colleagues for work on
the tammar wallaby [20], as well as others including sea lions
[14], poultry, and the hoatzin.
A natural progression of studies on soils, oceans, and
animal species was the studies on humans and the thousands
of microbes that inhabit the human body. Studies of the
human microbiome allow us to see the extent of microbial
diversity associated with the human body, differences by
Microbiomes
body site, age, ethnicity, and disease or health status. Two
large international studies and several smaller ones have
investigated the microbiota associated with the human body.
The National Institutes of Health completed a survey of the
human microbiome also known as the Human Microbiome
Project [11, 12] (https://commonfund.nih.gov/hmp/). The
healthy human microbiome revealed extensive diversity
between body sites and between people [11, 12]. The final
publications from this study represented a population of 242
healthy adults sampled at 15 or 18 body sites and provided
5,177 microbial taxonomic profiles from 16S rRNA genes
and over 3.5 terabases of metagenomic sequence. The study
design allowed for very streamlined sample collection,
DNA extraction, sequencing, and data analysis across all
the sequencing centers that were involved (Baylor College
of Medicine, JCVI, Broad, Washington University). As a
result, the data are quality controlled and standardized. The
study resulted in a baseline overview of the “healthy” hu-
man microbiome—essential for understanding how changes
in the microbiome influence or result in disease [9].
It is evident however that there is still a lot to be learned
about the interactions between humans and the microbes
that inhabit their bodies. Most of the studies that have been
performed to date have been limited by cohort size, geo-
graphic location, and representation of age, race, and differ-
ent diets. We expect that the wealth of information that we
have generated in the developed world on healthy people
will be a prelude to what we will learn from other parts of
the world.
Preliminary findings from a range of disease studies
suggest several relationships that were previously unknown.
We have learnt of associations with systemic disease, car-
diovascular disease [30], and the possible association with
and invasion of tumors by microbial species [3]. The micro-
biome is also being used as a biomarker to monitor inflam-
matory responses to human diseases [7]. As a scientific
community, we have described extensive microbial diversity
on all the human body surfaces, including a far more diverse
population than we knew before.
Animal models of the human body have shown potential
for evaluating human health—studies on aging have shown
that a single microbial species can be correlated with delays
in the aging process [29]. In the recent work of Virk and
colleagues [29], they were able to show clearly that restrict-
ing Escherichia coli in the diet of Caenorhabditis elegans
(by essentially reducing the availability of folate) extended
the life-span in C. elegans. They go on to propose that
manipulations to the gut to reduce folate availability can
possibly increase the life-span, i.e., a simple reduction of
folate via microbial manipulation could be one of the path-
ways to an extended life-span.
Clearly, we are a long way from completely understand-
ing the impact of the microbes that live on and in us, but the
917
field of human microbiology has been reinvigorated primar-
ily by improved technologies for processing and sequencing
DNA. We have also started to look more closely at existing
and new diagnostics, therapies, and the use of pre- and
probiotics in alleviating disease conditions. The studies of
the human microbiome, not unlike the studies of the human
genome, are still in their infancy, with larger cohort sizes
and more integrated “omics” approaches that incorporate the
transcriptome and metabolome, at a minimum, needed to
allow for a more holistic approach to address these questions
as it relates to human health.
What Has Genomics Taught Us About Oceans
and Human Health?
Just as sequencing approaches have been used to interrogate
humans, soils, and various animal species, these technical
approaches have been used to interrogate the bodies of
water associated with the planet. We are aware that the
world’s ocean systems are under stress due to overfishing
and pollution and other stressors that have been placed on
them by humans. Our oceans provide large populations with
food but continue to be bombarded with a multitude of other
problems. Oil spills are also common. The recent Deepwater
Horizon oil spill in the Gulf of Mexico is only one of several
examples of damage to our oceans caused by human
exploits. Several studies have been spawned to investigate
the impact of this oil spill on the environment in the gulf.
Hazen and colleagues for example performed a series of
studies where they applied various omics approaches to
investigate the impact of the oil spill. In the ISME 2012
study [16], they demonstrate changes in microbial commu-
nity composition and structure in the deep-sea oil plume,
demonstrated by an enrichment of genes associated with
hydrocarbon breakdown inside of the plume versus outside
of the plume.
Genomics approaches are being used to allow us to
understand our oceans better. Venter and colleagues revealed
extensive microbial diversity in their initial survey of the
Sargasso Sea, which went on to become the Global Ocean
Survey. These surveys have also launched several other stud-
ies focused on microbial diversity and using other omics
approaches such as transcriptomics and proteomics. Not only
are the bacteria in the ocean are being studied but also the
eukaryotes, viruses, and phage.
From metagenomes, we have gained insight into micro-
bial diversity, novel pathways, lateral gene transfer, and
viral activity in the oceans. Some genomes of previously
uncultured species have fallen out from metagenome sur-
veys. In the study of Iverson and colleagues [13], they were
able to generate the genome of an as-yet uncultured marine
group II Euryarchaeota—this genome was recovered from a
918
surface seawater metagenome. Other examples of the recov-
ery of almost complete genomes exist including from the
Global Ocean Expedition published in 2004 [28].
Several ocean microbial species have had complete
genomes sequence, and new approaches have been used to
recover the complete genomes of those species that have been
difficult to cultivate using traditional approaches. Single cell
genomics has been a successful approach to the recovery of
complete genomes [25]. The single cell approach basically
allows for the recovery of a large portion of a genome from a
species that we cannot cultivate successfully. The approach
complements existing tools to cultivate species but allows us
to recover genetic information from those that we cannot yet
culture and is very useful to characterize species that are
thought to play major or significant roles in environments
[25]. The approach has also been used to reveal close relation-
ships between uncultured protists and prokaryotes [15].
It is evident that the viruses that inhabit the planet and all the
associated ecosystems play critical roles. In the oceans, they
have been shown to regulate the movement of nutrients as a
result of host cell lysis. Viruses are a major component of the
oceans playing major roles in ocean processes. The new se-
quencing technologies are allowing for a more detailed evalu-
ation of viruses in our oceans. Metagenomics approaches have
been used in several studies to investigate viral populations
associated with different ocean samples almost as extensively
as used to evaluate bacterial populations in the oceans.
Genomics and many sequenced-based approaches are be-
ing used to evaluate the health of our plant and the humans
that inhabit it. Genomics and other approaches will be critical
to understanding the ocean as an ever-important ecosystem
and how we can maintain its productivity and health. Meta-
genomics surveys will undoubtedly continue to bring signif-
icant value to the study of environments. As sequencing costs
plummet and higher throughput is achieved with the newer
sequencing technologies, scientists will continue to use high-
throughput sequencing to evaluate the microbial communities
that they are most interested in. Bioinformatics approaches
will continue to improve and allow for greater insight into the
data that are being generated.
However, high-throughput sequencing of DNA samples
cannot reveal the functional capabilities of the species that
are present and is limited to a general description of the
genetic potential of a community. High-throughput sequenc-
ing or metagenomics does become invaluable however
when coupled with measurements of gene expression such
as in metatranscriptomics studies. Other approaches to eval-
uate genetic activity include metabolomics or proteomics.
When performed over a time series, these approaches allow
for an analysis of how community function changes during
the seasons, with temperature changes, etc. In the study of
Gilbert and colleagues [10], they investigated metatranscrip-
tomes that had been made from samples taken at two time
K. E. Nelson
points in a replicated mesocosm involving an induced phy-
toplankton bloom and were clearly able to validate the use
of this technology for the study of functional gene diversity
in the oceans.
Other approaches for understanding microbial physiolo-
gy such as the use of stable isotope probing (SIP) as de-
scribed in [27] will further allow scientists to investigate the
potential metabolic profiles of microbial species in their
environment and connect these processes with metagenomic
data and or individual phylogenetic markers. SIP has been
used to identify active community members in human and
other environmental samples [17, 27].
More organisms will continue to be sequenced, analyzed,
and studied giving even more insight into species behavior
and diversity in the oceans, and will be coupled to advanc-
ing approaches to studying and cultivating these species. All
of this is being accelerated because of bridges across the
sciences, where tools that are being developed on soils and
humans for example can readily be adapted to understand-
ing our oceans. All the approaches that have been described
here have become essential for describing microbial diver-
sity in the environment, understanding the ecology of these
species, and for the identification of novel biomarkers and
signature molecules.
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