Synergy among Microbiota and Their Hosts: Leveraging the Hawaiian Archipelago and Local Collaborative Networks To Address Pressing Questions in Microbiome Research

Abstract

Despite increasing acknowledgment that microorganisms underpin the healthy functioning of basically all multicellular life, few cross-disciplinary teams address the diversity and function of microbiota across organisms and ecosystems. Our newly formed consortium of junior faculty spanning fields such as ecology and geoscience to mathematics and molecular biology from the University of Hawai‘i at Mānoa aims to fill this gap. We are united in our mutual interest in advancing a new paradigm for biology that incorporates our modern understanding of the importance of microorganisms. As our first concerted research effort, we will assess the diversity and function of microbes across an entire watershed on the island of Oahu, Hawai‘i. Due to its high ecological diversity across tractable areas of land and sea, Hawai‘i provides a model system for the study of complex microbial communities and the processes they mediate. Owing to our diverse expertise, we will leverage this study system to advance the field of biology.

Full text

Synergy among Microbiota and Their Hosts: Leveraging the
Hawaiian Archipelago and Local Collaborative Networks To
Address Pressing Questions in Microbiome Research
Nicole A. Hynson,
a
Kiana L. Frank,
b
Rosanna A. Alegado,
c,f
Anthony S. Amend,
a
Mohammad Arif,
d
Gordon M. Bennett,
d
Andrea J. Jani,
c
Matthew C. I. Medeiros,
b
Yuriy Mileyko,
e
Craig E. Nelson,
c,f
Nhu H. Nguyen,
g
Olivia D. Nigro,
c
Sladjana Prisic,
h
Sangwoo Shin,
i
Daisuke Takagi,
e
Samuel T. Wilson,
c
Joanne Y. Yew
b
a
Department of Botany, University of Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
b
Pacific Biosciences Research Center, University of Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
c
Center for Microbial Oceanography: Research and Education, Department of Oceanography, University of
Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
d
Department of Plant and Environmental Protection Sciences, University of Hawai‘i at Ma៮noa, Honolulu,
Hawai‘i, USA
e
Department of Mathematics, University of Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
f
Sea Grant College Program, University of Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
g
Department of Tropical Plant and Soil Sciences, University of Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
h
Department of Microbiology, University of Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
i
Department of Mechanical Engineering, University of Hawai‘i at Ma៮noa, Honolulu, Hawai‘i, USA
ABSTRACT Despite increasing acknowledgment that microorganisms underpin the
healthy functioning of basically all multicellular life, few cross-disciplinary teams ad-
dress the diversity and function of microbiota across organisms and ecosystems. Our
newly formed consortium of junior faculty spanning fields such as ecology and geo-
science to mathematics and molecular biology from the University of Hawai‘i at
Ma៮noa aims to fill this gap. We are united in our mutual interest in advancing a new
paradigm for biology that incorporates our modern understanding of the impor-
tance of microorganisms. As our first concerted research effort, we will assess the di-
versity and function of microbes across an entire watershed on the island of Oahu,
Hawai‘i. Due to its high ecological diversity across tractable areas of land and sea,
Hawai‘i provides a model system for the study of complex microbial communities
and the processes they mediate. Owing to our diverse expertise, we will leverage
this study system to advance the field of biology.
KEYWORDS ecology, environmental microbiology, evolution, microbiome, paradigm
shift
A SCIENTIFIC IMPERATIVE
Crucial to science is understanding whether it is itself reductionist: do first principles
from one field, such as physics, explain the fundaments of others like molecular
biology? The answer to this question hinges upon whether scientists speak the same
language. Consortia that link multiple scientific fields offer the powerful promise of
extending any single individual’s research to a more globally unifying endeavor. We see
this as one of the potential primary outcomes of our newly established collaboration of
junior faculty, the Center for Microbiome Analysis through Island Knowledge and
Investigation (C-MAIKI). By overcoming the technical and philosophical barriers that
often silo disparate disciplines, our goal is to advance the field of microbial systems
biology. We are a diverse group of early career researchers from the University of
Hawai‘i at Ma៮noa who are fascinated by the microbial world. Our individual research
programs span natural environments, including sea, land, and freshwater, as well as
Received 30 October 2017 Accepted 28
November 2017 Published 13 March 2018
Citation Hynson NA, Frank KL, Alegado RA,
Amend AS, Arif M, Bennett GM, Jani AJ,
Medeiros MCI, Mileyko Y, Nelson CE, Nguyen
NH, Nigro OD, Prisic S, Shin S, Takagi D, Wilson
ST, Yew JY. 2018. Synergy among microbiota
and their hosts: leveraging the Hawaiian
archipelago and local collaborative networks to
address pressing questions in microbiome
research. mSystems 3:e00159-17. https://doi
.org/10.1128/mSystems.00159-17.
Copyright © 2018 Hynson et al. This is an
open-access article distributed under the terms
of the Creative Commons Attribution 4.0
International license.
Address correspondence to Nicole A. Hynson,
nhynson@hawaii.edu.
Conflict of Interest Disclosures: N.A.H. has
nothing to disclose. K.L.F. has nothing to
disclose. R.A.A. has nothing to disclose. A.S.A.
has nothing to disclose. M.A. has nothing to
disclose. G.M.B. has nothing to disclose. A.J.J.
has nothing to disclose. M.C.I.M. has nothing to
disclose. Y.M. has nothing to disclose. C.E.N.
reports grant OCE-1538393 from the U.S.
National Science Foundation and grant
NA14OAR4170071 from the National Oceanic
and Atmospheric Administration during the
conduct of the study. N.H.N. has nothing to
disclose. O.D.N. has nothing to disclose. S.P.
received grants NIH-NIAID R21 AI109293, HCF–
Leahi Fund–17ADVC-86185, and NIH-NIGMS
P30 GM114737 during the conduct of the
study. S.S. has nothing to disclose. D.T. has
nothing to disclose. S.T.W. has nothing to
disclose. J.Y.Y. has nothing to disclose.
mSystems® vol. 3, no. 2, is a special issue
sponsored by Janssen Human Microbiome
Institute (JHMI).
PERSPECTIVE
Ecological and Evolutionary Science
crossm
March/April 2018 Volume 3 Issue 2 e00159-17 msystems.asm.org 1

model laboratory systems, such as fruit flies and rodents, while our study organisms
range from viruses, bacteria, protists, and fungi to plants and animals, including
humans (1–6). Some of us are not even biologists in the traditional sense, but rather
mechanical engineers and mathematicians who look to nature to understand and
create complex systems (7–9). Together, we seek to illuminate the diversity and
function of microbes within Hawaiian ecosystems to examine whether their roles are
conserved across hosts and environments and the extent to which disturbances alter
the functioning of microbially mediated processes.
PLAYING CATCH-UP: A CRITICAL NEED FOR BASIC MICROBIOME RESEARCH
While concepts such as keystone species, ecosystem engineers, and diversity/
productivity relationships have been well documented for many macroorganisms, our
knowledge of these features of microbial communities is limited. Three of the persistent
challenges to assessing the ecology of microbes have been (i) ascribing meaningful
taxonomic units that can be used to test evolutionary and ecological theories, (ii)
disentangling the relative contributions of evolutionary and ecological processes to the
community assembly and function of microbes, and (iii) understanding the spatial and
temporal scales that are relevant for microbial interactions and the processes they
mediate (10). Given the ever-increasing amounts of genomic data that can be used to
determine the identity of microbes and the fact that evolutionary and population
genetics theories provide fundamental frameworks for examining ecological patterns,
solving the first two challenges seem relatively close at hand: it is just a matter of
choosing a biological scale that is relevant for microbes (that is, what is the appropriate
unit of selection for microorganisms?). Thus, we see the third challenge— deriving the
appropriate space-time scales for the study of microbes, their interactions with each
other, and their environments—as the most critical. We intend to make the most
progress toward addressing this challenge in the years to come.
HAWAI‘I AS A MODEL SYSTEM FOR THE STUDY OF MICROBIOMES
With our collective recognition that microbes underpin the healthy function of all
multicellular life, we have come together to take a multifaceted approach to bridging
two vast knowledge gaps in the quickly growing field of microbiome research: which
environments act as reservoirs for symbiotic microbes when they are outside the host,
and how we can manage our environments to promote and maintain healthy microbial
partnerships? We are uniquely positioned to address these questions due to our diverse
and complementary expertise, as well as our location on the island of O’ahu in the
Hawaiian archipelago. Hawai‘i has long been recognized by climatologists, ecologists,
and evolutionary biologists as a model system for the study of natural phenomena.
While covering only 0.004% of the Earth’s total land area (similar to the size of
Massachusetts), over a matter of kilometers, Hawaiian bioregions contain comparable
environmental diversity to that typically found on much larger spatial scales, like
continents. For example, Hawai‘i has a rainfall gradient from 204 mm/year on average
near the summit of Mauna Kea (similar to averages in the Gobi Desert in Asia), to
10,271 mm/year on average on the slopes of Haleakala៮(similar to parts of the
Chocó-Darién, Columbia, one of the wettest places on Earth). Because Hawai‘i is one of
the most remote island chains on Earth, non-human-assisted dispersal is a significant
hurdle for the establishment of most organisms. As a result, Hawai‘i’s macrobiota is
⬎90% endemic, with well-known evolutionary histories. While far less is known about
the diversity of Hawai‘i’s microbes, evidence from recent surveys suggests that its
microbial communities are dominated by taxa, at least to the generic level, found
throughout the world (11, 12). For example, a recent study of phyllosphere fungi
associated with a single genus of endemic Hawaiian plant Clermontia revealed that
communities are hyperdiverse, harboring thousands of fungal operational taxonomic
units (species equivalents). This result is similar to the findings of a global assessment
of foliar fungal endophytes where tropical ecosystems harbored the greatest relative
diversity (12, 13). Thus, Hawai‘i is a relatively small and closed system, with suites of
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environmental conditions similar to those found throughout the globe, and is occupied
by many of the same guilds of microorganisms also found elsewhere. We have the ideal
“living laboratory” for the study of microbiota and microbially mediated processes.
FORGING AHEAD WITH THE STUDY OF HAWAIIAN MICROBIOTA
While prior research on microbiomes has focused on changes in microbial diversity
across various environmental conditions in single hosts, we now recognize the con-
nectivity across habitats and hosts and the microbial “neighborhood” as critical drivers
of community composition (14)(Fig. 1). Through broad-scale sampling, we have
identified traits and taxonomy that predict nonrandom overlap of microbial community
members across disparate hosts and habitats (15, 16). For example, fungi in the genus
Malassezia have been identified as numerically dominant in most marine systems
examined throughout the Hawaiian Archipelago, yet some of the same genotypes
appear in soil, plant, and even air samples (11). Also, studies on Hawaiian insect-
microbe interactions have revealed that many host taxa selectively harbor distinct
microbial communities, some of which appear to be intrinsic to hosts’ use of environ-
mental resources and underpin their adaptation to Hawai‘i’s diverse environments (19).
This connectivity begs the following questions: what habitat(s) represent the regional
species pool, and are there conserved functions of these shared microbes across hosts
and habitats?
As a next step to elucidate the mechanisms underlying these patterns of connec-
tivity, we plan to assess the community dynamics of microbes as they transition from
free-living to symbiotic states across an entire watershed, including the macrobiota
living in it, that spans mountain ridges to fringing coral reef habitats (Fig. 1). Using a
diversity of -omic approaches, as well as assays such as extracellular enzyme and lipid
production to assess microbial functional traits, we will determine the identity and
functional flexibility of microbes across hosts and habitats and how this impacts host
FIG 1 Conceptual schematic of C-MAIKI’s approach to address pressing questions in microbiome research by evaluating synergy (red arrows) among
environmental microbiota and their hosts—from free-living to symbiotic lifestyles—leveraging the unique and replicable gradients across Hawaiian water-
sheds—from mountain (terrestrial) to sea (marine) habitats. Recognizing that microbes underpin the healthy function of all multicellular life, this synergistic
cross-disciplinary approach allows us to address what environments act as reservoirs for symbiotic microbes when they are outside the host and how we can
manage our environments to promote and maintain healthy microbial partnerships.
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and environmental health. Through manipulative field and laboratory experiments
within and outside hosts and across steep environmental gradients, we will then test
the resilience of microbial communities to perturbations in their living conditions.
These data will provide the training ground for predictive probabilistic models that
identify how we may manipulate microbial communities to restore or elicit specific host
functions or ecosystem states. Using population genomic approaches combined with
classic tools from population genetics and coalescent theory, we hope to advance our
understanding of microbial migration and source-sink relationships for microbes, in-
cluding how transitions from drastically different environments (e.g., terrestrial to
marine) or hosts (e.g., corals to insects) are made.
NO LONGER THE BLACK BOX: THE FUTURE IS BRIGHT FOR MICROBIOLOGY
Over the next 5 years, the field of microbiology has much to contribute, as well as
much to learn, from the broader scientific community and disciplines. In the same vein
as Thomas Kuhn’s The Structure of Scientific Revolutions (17), we would argue that the
field of biology, until fairly recently, was in a stage of “normal science” where our
interest in, and understanding of, the microbial world had been observed through
the lens of macrobiology. Brought on by the immense technological innovations in
DNA sequencing, we are shining a bright floodlight on the previously hidden world
of microbes and its fundamental role in shaping ecosystems across all trophic levels.
We are now in the early stages of a paradigm shift, the boundaries of which are only
beginning to be delineated. In the years to come, we anticipate this paradigm shift
being fueled by novel technologies and their ease of use, such as single-molecule
sequencing, single-cell sorting from environmental communities, and increasingly
streamlined computational platforms for large data sets. However, for this shift to
become fully realized, it will not only require that we integrate microbes into
(macro)biological concepts, but that we create new theories, models, and collab-
orations. As a cohort, the C-MAIKI faculty envisions the development of a new
framework for biology that leverages our study system and our cross-disciplinary
interactions to lay this new foundation.
COLLABORATIONS, LIKE MICROBIOMES, ARE MORE THAN THE SUM OF THEIR
INDIVIDUAL PARTS
On the flip side of reductionism is synergism, or the concept popularized by the field
of ecology, that the additive effects of interacting organisms result in something more
than the sum of their individual constituents. The classic example of synergism is the
significant and positive relationship between plant diversity and primary productivity
(18). While the cause for such synergism even among well-studied macroorganisms still
remains somewhat elusive, our research endeavors will shed new light on the emergent
properties of microbiomes. For example, collaborations among those of us who focus
on model systems and those who work in field settings can transform our understand-
ing of basic physiological and evolutionary processes. By using well-studied organisms
such as Drosophila spp. in manipulative field experiments, we can elucidate the
molecular mechanisms by which environmental microbes alter the physiology and
phenotype of their hosts. Our collaborations will not only build a means for cross-
communication among disciplines, perhaps revealing the reductionist side of micro-
biomes, but they will also result in synergistic breakthroughs that allow us to answer
some of the most pertinent questions in the life sciences.
ACKNOWLEDGMENTS
We thank the Office of the Vice Chancellor for Research at the University of Hawai‘i
at Ma៮noa for funding. This paper is funded in part by a grant/cooperative agreement
from the National Oceanic and Atmospheric Administration (NOAA), project R/WR-3,
which is sponsored by the University of Hawai‘i Sea Grant College Program, SOEST,
under institutional grant no. NA14OAR4170071 from NOAA’s National Sea Grant Office,
Department of Commerce.
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The views expressed herein are those of the authors and do not necessarily reflect
the views of NOAA or any of its subagencies.
This is publication number 10279 of the School of Ocean and Earth Science and
Technology of the University of Hawai‘i at Ma៮noa and publication UNIHI-SEAGRANT-
JC-16-13 of the University of Hawai‘i Sea Grant College Program.
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