Hea-Jong Chung

Hyeon-Jin Kim

Seong-Tshool Hong

Thi T. B. Nguyen

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OPINION
published: 06 July 2018
doi: 10.3389/fmicb.2018.01510
Frontiers in Microbiology | www.frontiersin.org 1 July 2018 | Volume 9 | Article 1510
Edited by:
Zhaoping Li,
Ronald Reagan UCLA Medical Center,
United States
Reviewed by:
Daniela Fiocco,
University of Foggia, Italy
Pasquale Russo,
University of Foggia, Italy
*Correspondence:
Seong-Tshool Hong
seonghong@chonbuk.ac.kr
Specialty section:
This article was submitted to
Food Microbiology,
a section of the journal
Frontiers in Microbiology
Received: 01 December 2017
Accepted: 18 June 2018
Published: 06 July 2018
Citation:
Chung H-J, Nguyen TTB, Kim H-J
and Hong S-T (2018) Gut Microbiota
as a Missing Link Between Nutrients
and Traits of Human.
Front. Microbiol. 9:1510.
doi: 10.3389/fmicb.2018.01510
Gut Microbiota as a Missing Link
Between Nutrients and Traits of
Human
Hea-Jong Chung 1, Thi T. B. Nguyen 1, Hyeon-Jin Kim 2 and Seong-Tshool Hong 1*
1Department of Biomedical Sciences, Institute for Medical Science, Chonbuk National University Medical School, Jeonju,
South Korea, 2 JINIS BDRD Institute, JINIS Biopharmaceuticals Co., Wanju, South Korea
Keywords: gut microbiota, nutrients, human traits, diet, disease
CONTRIBUTION OF GUT MICROBIOTA IN DETERMINING
HUMAN DISEASES
With the development of next generation sequencing (NGS) technology, the role of gut microbiota
in human health has been extensively studied. Metagenome sequencing analysis, which is based on
NGS, and subsequent statistical analysis showed that the relationship between gut microbiota and
humans is not merely commensal but rather a mutualistic relationship (Chen et al., 2013; Jandhyala
et al., 2015). Recent advances in the field of gut microbiota are elucidating our understanding of
human biology.
The microbiota of the human gut is a massive and complex microbial community consisting
of 100 trillion microbes in the intestine. The gut microbiota is essential to the health and well-
being of the host (Marchesi et al., 2016). Although interactions between gut microbiota and its host
have negative effects in some cases, these interactions positively affect the host in most cases. It is
now clear that the gut microbiota contributes significantly to the traits of humans as much as our
genes, especially in the case of atherosclerosis, hypertension, obesity, diabetes, metabolic syndrome,
inflammatory bowel disease (IBD), gastrointestinal tract malignancies, hepatic encephalopathy,
allergies, behavior, intelligence, autism, neurological diseases, and psychological diseases (Chen
et al., 2013; Nguyen et al., 2017; Zhang et al., 2017; Table 1). It has also been found that alteration
of the composition of the gut microbiota in its host affects the behavior, intelligence, mood, autism,
psychology, and migraines of its host through the gut-brain axis (Chen et al., 2013). Thus, the effect
of the gut microbiota on human phenotypes has become a booming area of research and presents
a new paradigm of opportunities for medical and food applications.
THE GUT MICROBIOTA OF HUMANS FLUCTUATES IN
RESPONSE TO NUTRITIONAL UPTAKE RATHER THAN
REMAINING STABLY IMMUTABLE THROUGHOUT LIFE
Recent studies have elucidated that the gut microbiota plays essential roles in the health and
well-being of its host, and whether the composition of the gut microbiota fluctuates or stays
constant throughout the lifetime of its host has become one of the main questions to ponder in
the scientific community. The prevailing opinion has been that the gut microbiota develops rapidly
right after birth and fluctuates only until it matures, which usually takes∼2 years after birth (Koenig
et al., 2011). Once the gut microbiota is established, its composition remains stably immutable
throughout life. However, recent evidence shows that this opinion is wrong, and the composition
of gut microbiota can fluctuate during the lifetime of its host (Wu et al., 2011; David et al., 2014).
Chung et al. Gut Microbiota as a Missing Link
It is observed that the growth of almost all
microbial organisms is very sensitive to their ambient nutrients.
Additionally, considering the diversity and number of microbes
in the gut microbiota, it would be more reasonable to speculate
that the composition of the gut microbiota could constantly
fluctuate, reflecting the diet of its host. Wu et al. recently showed
that the long-term consumption of different diets, such as
plant-based diets or animal-based diets, drastically altered the
composition of gut microbiota, even at the phylum level in
the taxonomic hierarchy (Wu et al., 2011). Vegetarian diets
consist of fibers containing resistant starch and non-starch
polysaccharides. Interestingly, numerous studies have shown
that vegetarian diets increased the abundance of carbohydrate-
degrading microbes, such as Prevotella, Roseburia, Eubacterium
rectale, and Ruminococcus bromii, in their gut microbiota (Wu
et al., 2011; David et al., 2014). In contrast, western diets high
in protein and fat, which promote chylomicron and bile acids,
increase the abundance of bile acid-tolerant microbes, such
as Alistipes, Bilophila, and Bacteroides, in their gut microbiota
(David et al., 2014). A defined food consumption experiment by
David et al. even showed that the composition of gut microbiota
is promptly affected by the dietary fluctuations within a day. Even
cyclical shifts in daily feeding or fasting affected the increase of
specific genera in the gut microbiota (David et al., 2014). These
studies clearly show that the composition of the human gut
microbiota constantly fluctuates in response to the nutritional
composition of the diet rather than remaining stably immutable
throughout life.
NUTRIENTS AFFECT THE COMPOSITION
OF THE GUT MICROBIOTA, AND BOTH
MODIFIED GUT MICROBIOTA AND
NUTRIENTS AFFECT HUMAN TRAITS
TOGETHER
Nutrients are dietary components that an organism metabolizes
for survival and growth. Nutrients are substances that provide
energy and/or form a component of body tissues. Higher
organisms, such as humans, intake nutrients in their diets to
maintain the precisely functioningmetabolic machinery affecting
the health and well-being of the organism. Because nutrients
are essential substances for sustaining life, there is much less
genetic variation in the genes involved in processing nutrients
compared to other genes in humans (Fraser, 2015). Considering
that nutrients absorbed by an organism are precisely processed
by the well-orchestrated metabolic machinery in the bodies of
organisms, diets have a limited ability in terms of affecting
the traits of human. However, epidemiological research has
proven that diet significantly affects human traits (Sharief et al.,
2011; Boada et al., 2016). The quantity of calories and dietary
patterns are key determinants of the anthropometric quantitative
traits, which are especially reflected in the positive height
trend in the developed countries (Jelenkovic et al., 2016). In
the context of the nature of nutrients, an association between
anthropometric quantitative traits and nutrients is expected.
Interestingly, the effect of nutrients on human traits is not limited
TABLE 1 | Effect of the gut microbiota on human diseases.
Disease/
disorder
Implicated microbiota Potential role of the microbiome
METABOLIC DISEASES
Obesity Firmicutes/Bacteroidetes ratio
Prevotellaceae
Eubacterium
Faecalibacterium
Roseburia
Significant changes in gut microbiota
are associated with increased
obesity
Type II diabetes Bacteroidetes/Firmicutes
Bacteroides-Prevotella
Eggerthella lenta
Clostridia
Eubacterium rectale
Faecalibacterium prausnitzii
Roseburia intestinalis
Roseburia inulinivorans
Shifts in gut microbiota are
associated with increases in plasma
glucose concentrations
Hypertension Prevotella
Klebsiella
Bifidobacterium
Butyrivibrio
Coprococcus
Faecalibacterium
Roseburia
Gut dysbiosis increases hypertension
IMMUNE DISEASES
IBD Bacteroidetes
Lachnospiraceae
Actinobacteria
Proteobacteria
Clostridium leptum
Clostridium coccoides
Faecalibacterium prausnitzii
Firmicutes/Bacteroidetes ratio
Bifidobacteria
Immune response to the gut
microbial community
Composition of the gut microbiota
contributes to inflammation
Allergies Lactobacillus spp.
Bifidobacterium adolescentis
Clostridium difficile
Early colonization with Lactobacillus
is associated with decreased
allergies
Early colonization with more diverse
microbiota might prevent allergies
Celiac disease Bacteroides vulgatus
Escherichia coli
Clostridium coccoides
High diversity in Celiac disease
patients vs. control
Type I diabetes Bacteroides
Streptococci
Clostridium cluster IV and XIVa
Interaction between the gut
community and the innate immune
system may be a predisposing factor
for diabetes
Rheumatoid
arthritis
Bifidobacteria
Bacteroides
Porphyromonas
Prevotella
Bacteroides fragilis
Eubacterium rectale
Clostridium coccoides
Treg-promoting organisms depleted;
overgrowth of bacteria that induce
Th17 cell populations, leading to
inflammation
Intestinal microbes associated with
etiology
Atopy and
asthma
Bifidobacteria
Bacteroides
Staphylococcus spp.
Streptococcus spp.
Enterobacteria
Clostridium difficile
Pre- and post-natal microbial
exposure appear key to appropriate
immune development
Mode of delivery and nutrient uptake
are important factors for GI
community development and
protection against subsequent
atopic disease development
AUTISM
Autism Clostridial species Increased bacterial diversity in the
feces of autistic children compared
to control
PSYCHOLOGICAL DISEASE
Anxiety and
depression
Lactobacillus reuteri
Lactobacillus rhamnosus
Bifidobacterium infantis
Decreased anxiety and
stress-induced increase of
corticosterone
Frontiers in Microbiology | www.frontiersin.org 2 July 2018 | Volume 9 | Article 1510
Chung et al. Gut Microbiota as a Missing Link
FIGURE 1 | The schematic diagram on how nutrients affect the human traits through gut microbiota.
to anthropometric quantitative traits. Studies on monozygotic
twins show that nutrients strongly affect various metabolic
diseases and immune diseases (Rissanen et al., 2002; Spehlmann
et al., 2012). Epidemiological research has shown that nutrients
are considered a fundamental factor along with genetics in the
development and/or prevention of rheumatoid arthritis, multiple
sclerosis, asthma, and allergies (Sharief et al., 2011; Thorburn
et al., 2014). In addition, numerous studies have proven an
association between cancer and nutrients (Boada et al., 2016).
Because of the clear association between cancer and nutrients,
the World Health Organization (WHO) and the International
Agency for Research on Cancer (IARC) even declared that
hydrogenated oils, potato chips, processed meats, red meats,
farmed salmon, and refined sugar are associated with various
cancers. These results definitely indicate that human traits are
also strongly shaped by nutrients. In this sense, the opinion of
“we are what we eat” by the general public would be scientifically
wise. Despite the expectation that nutrients only slightly affect
human traits, it is surprising to observe that nutrients seem to
affect human traits as much as our own genes, which suggests
that there might be a strong link between nutrients and human
traits.
Recent scientific evidence regarding the gut microbiota makes
it possible to explain the link between nutrients and human traits.
The gut microbiota not only directly interacts with the somatic
cells of its host to affect the traits of human, as in the case
of training immunological networks, but also generates various
chemicals, which can directly modify the biochemical pathways
of humans. The composition of the gut microbiota fluctuates
based on the nutrient uptake of its host, and the composition of
the gut microbiota affects various human traits as much as our
genes (Figure 1). Therefore, it is reasonable to speculate that the
effect of nutrients on human traits would be the combined results
from both the gut microbiota modified by the nutrient uptake
and the nutrients themselves. We believe that the gut microbiota
is themissing link between nutrients andmodifications of human
traits.
AUTHOR CONTRIBUTIONS
S-TH conceived the idea and designed the structure of the
manuscript. H-JC, TN, and S-TH drafted the manuscript, table
and figure. All authors have critically read, corrected, and
approved the final version of the manuscript and agree with the
opinions expressed here.
FUNDING
This research was financially supported by the Global
accompanied growth R&BD program (N042600010) through
the Ministry of Trade, Industry and Energy (MOTIE,
Korea).
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Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Copyright © 2018 Chung, Nguyen, Kim and Hong. This is an open-access article
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No use, distribution or reproduction is permitted which does not comply with these
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