Download The Human Gut Microbiome: Implications for Future Health Care

The Human Gut Microbiome:
Implications for Future Health Care
James M. Kinross, MRCS , Alexander C. von Roon, MRCS ,
Elaine Holmes, PhD, MRSC, Ara Darzi, FMedSci, HonFREng, KBE ,
and Jeremy K. Nicholson, PhD, FRSC, FRC Path
Corresponding author
Prof. Jeremy K. Nicholson
Department of Biomolecular Medicine, Faculty of Medicine,
Imperial College, 6th Floor, Sir Alexander Fleming Building,
South Kensington Campus, London SW7 2AZ, United Kingdom.
E-mail: [email protected]
Current Gastroenterology Reports 2008, 10:396 – 403
Current Medicine Group LLC ISSN 1522-8037
Copyright © 2008 by Current Medicine Group LLC
In their intestine, humans possess an “extended genome”
of millions of microbial genes—the microbiome. Because
this complex symbiosis influences host metabolism, physiology, and gene expression, it has been proposed that
humans are complex biologic “superorganisms.” Advances
in microbiologic analysis and systems biology are now
beginning to implicate the gut microbiome in the etiology
of localized intestinal diseases such as the irritable bowel
syndrome, inflammatory bowel disease, and colon cancer.
These approaches also suggest possible links between
the gut and previously unassociated systemic conditions
such as type 2 diabetes and obesity. The elucidation of
the intestinal microbiome is therefore likely to underpin
future disease prevention strategies, personalized health
care regimens, and the development of novel therapeutic
interventions. This review summarizes the research that is
defining our understanding of the intestinal microbiome
and highlights future areas of research in gastroenterology
and human health in which the intestinal microbiome will
play a significant role.
Introduction
In accordance with Koch’s postulates of the 1800s, medical science has largely held the view that one organism is
associated with one infectious disease (eg, Mycobacterium
tuberculosis infection). In the 1980s, the Nobel laureates
Barry Marshall and Robin Warren introduced the concept
that a bacterium, Helicobacter pylori, causes a seemingly noninfectious condition, peptic ulcer disease. This
connection is not surprising when one considers that all
vertebrates have co-evolved to a state of mutual interdepen-
dence with the microbial consortia that inhabit their body
surfaces and cavities. The human colonic microbiota comprises a consortium of many hundreds of bacterial species,
unique to each individual host, which changes in response
to diet, pharmaceutical input, age, disease, and medical or
surgical intervention. Most of these bacteria are anaerobic
and metabolize dietary compounds and ingested foreign
compounds (xenobiotics) that escape catabolism in the
upper gut. They are also essential to the enterohepatic circulation of compounds detoxified by the liver and released
in bile. The resident microbiota carries out an array of
enzymatic reactions, many distinct from but essential to
human genome–encoded activities. In essence, therefore,
mammals possess an “extended genome” of millions of
microbial genes—the microbiome—located in the intestine
[1]. This symbiotic condition influences host metabolism
and physiology as well as host gene expression, and it has
been proposed that humans are in fact a vastly complex,
biologic “superorganism”[2].
Contemporary classification of human disease states
derives from observed correlations between pathologic
analysis and clinical syndromes. In the postgenomic era,
novel systems-networking approaches are determining the
complex links among previously unassociated sets of genes
[3•]. However, these do not account for the role of the
microbiome and its influence on the human phenotype.
The notion of microbial-mammalian metabolic cooperation has therefore been defi ned through the concept of the
human metabonome [4•]. This term refers to the sum of
all the cellular metabolomes (the full set of metabolites
within, or that can be secreted by, a given cell) and their
interactions in a multicellular organism plus the products
of facile chemical transformations and extragenomically
generated metabolites. Such transgenomic, co-metabolic
interactions greatly increase system complexity and perhaps provide the ultimate challenge to understanding the
impact of intestinal microbiota modulation on the host
gut and human health [5••]. Advances in bioinformatics
and analytic biology are now allowing researchers to
measure the influence of the intestinal ecosystem, with the
implication that clinicians will no longer be restrained by
inadequate culture techniques and nonspecific metabolic
The Human Gut Microbiome: Implications for Future Health Care Kinross et al.
tests of microbial activity. Most importantly, in the
“omics” era, we may succeed in identifying and characterizing the phylogenetic makeup of the gut microbiota,
and it may be possible to accurately correlate microbiome
function with patient outcome. Scientific interest in the
human microbiome is so intense that the US National
Institutes of Health recently committed $115 million to
launching the Human Microbiome Project, which aims
to characterize the microbial components of the human
genetic and metabolic landscape using molecular techniques [6]. Part of this project aims to identify a “core
human microbiome,” a set of microbial genes, common
to all humans, without which humans cannot survive.
Metagenomic and metabonomic strategies are already
beginning to confi rm links to localized intestinal diseases
such as the irritable bowel syndrome (IBS) [7•], inflammatory bowel disease (IBD) [8], and colon cancer [9].
These approaches also suggest possible links between the
gut and previously unassociated systemic diseases such as
type 2 diabetes [5••]. This review summarizes the research
defi ning our understanding of the intestinal microbiome
and highlights future areas of research in gastroenterology and human health in which the intestinal microbiome
will play a significant role.
The Intestinal Ecosystem
The human intestine carries about 100 trillion microorganisms representing up to 1000 separate bacteria,
yeasts, and parasites. The upper gastrointestinal tract has
a sparse population as a result of the luminal medium and
propulsive forces, but the large bowel contains about 1 ×
1013 to 1 × 1014 microbes, weighing around 1.5 kg and carrying at least 100 times as many genes as our own genome
[10•]. This impressive bacterial load is turned over every
3 days and possesses an active biomass similar to a major
human organ [11•].
There is wide spatial and temporal variation within the
same intestine and between individuals, ages, cultures, and
sexes [12]. Although four phyla (Firmicutes, Bacteroidetes,
Actinobacteria, and Proteobacteria) dominate the human
microbiota and are relatively constant across individuals,
the makeup of a person’s microbiota at the species and
strain levels can be as individual as a fingerprint; we may
share as little as 1% of the same species [13]. Each host
thus has a unique, genetically determined response to both
aggressive and protective bacterial species.
The gut flora is vital for intestinal growth and development and for the health of the host in general. Through
resource competition, established symbionts protect the
host from colonization by potential pathogenic microorganisms. The gut microflora not only makes otherwise
inaccessible nutrients available; it is intimately involved
with mammalian metabolism. Experiments comparing
conventional mice with germ-free animals colonized by
human bowel flora show that the gut flora appears to
397
modulate both the enterohepatic circulation of bile acids
and lipid metabolism in the host [14].
The intestinal epithelium is composed of three barriers
in one: a physical barrier, an innate immune barrier, and
an adaptive immune barrier. The relationship between
commensal gut flora and the intestinal barrier is complex and occurs at all levels. Commensal microbes such
as bifi dobacteria not only maintain the mucosal barrier;
they also facilitate interkingdom signaling across it. The
human gastrointestinal mucosa is uniquely adapted to
the proximity of a massive load of potentially antigenic
microbes. Specialized mucosal immune cells continually
sample intestinal microbes and initiate local immune
responses without inducing a systemic response [15] by
inhibiting nuclear factor (NF)-κ B activation. If inappropriately activated, floral immune-mediated cytokines have
multiple actions, including altered epithelial secretion,
exaggerated nociceptive signaling, and abnormal motility.
The commensal flora uses a large repertoire of molecular processes to exert its beneficial health effects on the
host. In vitro, many commensal strains can produce antimicrobial substances such as hydrogen peroxide, cresols,
organic acids, bacteriocins, or bacteriocin-like molecules.
They also block adhesion of certain pathogenic bacteria,
modulate the host immune response via upregulation of
phagocytic activity, and stimulate the production of nonspecific and specific secretory IgA. Further stabilization
of the intestinal barrier is promoted by the stimulation of
mucus production and the attenuation of the inflammatory response.
The bifi dobacteria (Bifi dobacterium longum in particular) appear to play key roles within the gastrointestinal
microbial ecosystem. Bifi dobacteria ferment oligosaccharides, often liberated from more complex polysaccharides
by the Bacteroides, to produce short-chain fatty acids such
as acetate and lactate, which in turn are converted into
butyrate, the main energy source for the colonic mucosa,
by other dominant members of the gut microflora. Bifi dobacterium longum downregulates inflammatory cytokine
secretion in inflamed mucosal tissues from ulcerative
colitis patients ex vivo [16].
Metabonomic and Metagenomic Techniques
About 70% of the human microbiota cannot be identified or cultured by conventional microbiologic analyses
that rely on growing colonies of organisms on agars [17 ].
Metagenomic and metabonomic techniques have completely revolutionized the study of the microbiota. The most
important of these techniques are summarized below.
16S ribosomal RNA gene sequencing
The 16S ribosomal RNA (rRNA) gene is found in all microorganisms, and its hypervariable sections make it ideal for
microbe identification down to the species and strain level.
Following extraction, microbial rRNA is amplified using
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Gastrointestinal Infections
Figure 1. Transgenomic human microbiome–metabonome linkage. By using
computational multivariate analytic
techniques such as orthogonal–partial
least squares (O-PLS) analysis, it is possible to correlate metabonomic responses
with those of the intestinal microbiome.
DGGE—denaturing gradient gel electrophoresis; NMR—nuclear magnetic resonance;
PCR—polymerase chain reaction. (Adapted
from Li et al. [20•], with permission.)
polymerase chain reaction (PCR), fragments are aligned,
and the full sequence is compared with a publicly available
database for species identification [17 ].
Fluorescent in situ hybridization
Fluorescent in situ hybridization (FISH) uses DNA probes
that bind to species-specific rRNA gene sequences in
microorganisms. The DNA probe is tagged with a compound that will fluoresce only if the probe has attached to
the microbial rRNA. This allows enumeration of specific
microbial taxa under an ordinary light microscope and
quantitative comparisons between experimental groups.
Denaturing gradient gel electrophoresis
Denaturing gradient gel electrophoresis (DGGE) allows
analysis of rapid comparative shifts in microbial populations between experimental groups. As a first step,
microbial rRNA is amplified with PCR. The amplified
RNA fragments are then placed on a gel, which is run on a
denaturing agent, usually urea. RNA fragments of different
lengths separate out as discrete bands. Bands that account
for variation between experimental groups may then be
sampled from the gel, re-amplified using PCR, sequenced,
and identified using the technique described above.
Metabonomics
Metabonomics, a rapidly evolving field of biomedical
science, is defi ned as “the quantitative measurement of
time-related multiparametric metabolic responses of multicellular systems to pathophysiological stimuli or genetic
modification” [18]. In practice, it involves the use of spectroscopic metabolic profiling methods applied to various
body compartments, including urine, plasma, stool, and
tissue [19], coupled with multivariate statistical analysis
of the data. Metabonomics provides a systems approach
for studying in vivo metabolic profi les. High-throughput
methods such as high-resolution 1H nuclear magnetic
resonance (NMR) spectroscopy or mass spectrometry
(MS) can be used to generate a metabolic “fingerprint”
of biologic fluids or tissues reflecting the levels of hundreds or thousands of metabolites (molecular weight
< 1000 Da). By using chemometric tools to analyze these
complex metabolic data sets, latent information of prognostic and diagnostic use can be extracted and panels of
biomarkers can be associated with specific pathologies. A
number of urinary metabolites are of microbial origin, so
urinalysis provides a window into the microbial activity in
the gut. Using multivariate statistical approaches, it is now
possible to establish correlation or covariance patterns
between the metabonomic and metagenomic data (Fig. 1)
and in this way to generate hypotheses relating to the influence of particular bacterial species on biofluid metabolite
profiles and vice versa [20•].
Evidence for the Influence of the
Gut Microbiome on Gastrointestinal Diseases
Inflammatory bowel disease
The resident bacterial flora has been suggested as an
important factor that drives the inflammatory process in
IBD [21]. The mechanism by which the human gut immune
system discriminates between commensals and pathogens
is complex, involving ingestion of luminal organisms by M
cells, the presentation of bacterial antigens via dendritic
cells to intestinal B cells, and production and secretion
of IgA into the intestinal lumen. The NOD2/CARD15
gene, which is mutated in 17% to 25% of patients with
Crohn’s disease, partly controls this process [22]. Patients
The Human Gut Microbiome: Implications for Future Health Care Kinross et al.
with IBD also have increased intestinal mucosal secretion of IgG against a wide spectrum of commensals. IgG,
which activates the complement cascade, is much more
damaging to the intestinal mucosa than IgA. Patients
with IBD also have more bacteria from diverse genera
attached to their gut epithelial surfaces than do healthy
controls. Some of these, particularly bacteroides, were
found to penetrate into the epithelial layer, at times intracellularly [23]. Some anaerobes, particularly Bacteroides
fragilis and Clostridium ramosum, can induce fibrogenic
responses when invading the intestinal wall. Fecal stream
diversion has been shown to prevent recurrence in Crohn’s
disease, whereas infusion of bowel contents into excluded
ileal segments can re-activate mucosal lesions. Similarly,
patients with ulcerative colitis rarely have terminal ileitis,
whereas up to 50% develop pouchitis after proctocolectomy and ileal pouch formation. One of the proposed
mechanisms is increased fecal stasis and increased contact
time of intestinal contents with the ileal pouch mucosa. In
rodent models, IBD does not occur in germ-free animals,
in contrast to their naturally colonized littermates [8].
Colorectal cancer
Evidence suggests that the gut microbiota may play an
important role in modulating the effects of diet as an environmental risk factor for colorectal cancer. High dietary
consumption of fat and red meat (especially processed meat)
is associated with increased risk of colorectal cancer, an
effect thought to be modulated by N-nitroso compounds
and heterocyclic aromatic amines [24]. Heterocyclic amines
induce damage to DNA in colonocytes; some intestinal
microbes substantially increase this damage, whereas other
bacteria can take up and detoxify such compounds. In
animal studies, bacteria of the bacteroides and clostridium
genera increase the growth rate of colonic tumors, whereas
lactobacilli and bifidobacteria prevent tumorigenesis
[25,26]. Superoxide-producing Enterococcus faecalis has
conclusively been shown to produce epithelial cell damage.
Sulfate-reducing bacteria are also thought to be implicated,
with a similar mechanism, but conclusive evidence is lacking
[9]. These findings are supported by a human study, which
found higher levels of Bacteroides vulgatus and Bacteroides stercoris in people with a high risk of colon cancer, and
higher levels of Lactobacillus acidophilus and Lactobacillus
S06 in people at low risk of colon cancer [27].
399
Several studies have suggested the presence of qualitative changes in the colonic flora in IBS patients; the most
consistent fi nding is a relative decrease in the population of bifi dobacteria. Recently, the fecal microbiota
of patients with IBS symptoms was compared by 16S
rRNA gene analysis with that of age- and sex-matched
asymptomatic volunteers [7•]. Significant differences
were demonstrated, as were differences between the
clone libraries in several bacterial species belonging to
the genera Coprococcus, Collinsella, and Coprobacillus.
IBS is often linked to extensive gas production in the
colon, and some bacterial groups are more prone to gas
production than others. Therefore the composition and
activity of clostridial species has been specifically investigated using similar techniques [29]. The Clostridium
coccoides–Eubacterium rectale group was the dominant
subgroup of clostridia, contributing a mean of 43% of the
total bacteria in control subjects and 30% (constipation
type) to 50% (diarrhea type) in IBS subjects. The DGGE
profi les of IBS patients also indicated greater instability of
bacterial populations compared with controls.
A small percentage (6%–17%) of patients develop
postinfective IBS, with symptoms appearing for the fi rst
time after an acute episode of infective gastroenteritis,
which appears to be directly responsible for low-grade
immune activation [30]. Postinfective IBS appears to be a
nonspecific response to injury and has been reported after
Salmonella, Campylobacter, and Shigella infections.
Although IBS has generally been considered a motility disorder, it seems likely that the condition may involve
changes in epithelial fluid and electrolyte transport.
Bile acid malabsorption has been observed in 33% of
patients with diarrhea-predominant IBS. An NMRbased metabonomic strategy was employed in a mouse
model of postinfective IBS to study the metabolic effects
of Lactobacillus paracasei on gut dysfunction. Plasma
metabolic profi les of animals infected with Trichinella
spiralis showed increased energy metabolism, fat mobilization, and a disruption of amino acid metabolism due to
increased protein breakdown; these effects were related to
intestinal hypercontractility [31]. L. paracasei treatment
normalized the muscular activity and the disturbed energy
metabolism, suggesting that it may be possible to create a
noninvasive, metabolic, prognostic profi le to determine
which patients are at risk of developing postinfective IBS.
Irritable bowel syndrome
Although current defi nitions of IBS specify that there are
no structural or biochemical abnormalities to account
for the symptoms, there is growing evidence that floralmucosal interactions, the enteric nervous system, and the
brain-gut axis are directly involved in its pathogenesis.
This idea is based partly on fi ndings that antibiotic use
may predispose to IBS or exacerbate symptoms [28], and
that manipulation of the gut flora by prebiotics or probiotics may ameliorate them.
Evidence for the Influence of the
Gut Microbiome on Systemic Disease States
Obesity and the metabolic syndrome
Between 1980 and 2004, the prevalence of obesity in the
United States increased from 15% to 33% in adults and
from 6% to 19% in children [32]. Type 2 diabetes mellitus is the most significant cause of morbidity in obese
patients; it is often referred to as “diabesity.” This metabolic syndrome is thought to occur by a progressive defect
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in insulin secretion coupled with a progressive rise in
insulin resistance. Numerous mechanisms contribute to
insulin sensitivity regulation throughout disparate tissue
groups (skeletal muscles, fat, liver). Genomic strategies
have now begun to highlight candidate single nucleotide
polymorphisms (SNPs) responsible for insulin resistance
through genome-wide association studies. However, the
biocomplexity of the diabetes/obesity axis is significantly
influenced by sociologic, cultural, and environmental factors not accounted for by the human genome.
Although “infectobesity” arising from viral infection has
been previously described in numerous animal models, there
is increasing evidence that the intestinal microbiome is one
of the most significant environmental factors associated with
obesity and the metabolic syndrome. Conventionalized animals have 40% more body fat than germ-free animals and
diet is known to modulate gut-microbial composition [33].
Bacteroides thetaiotaomicron, a dominant member of the
normal distal intestinal microbiota, hydrolyzes otherwise
indigestible dietary polysaccharides and supplies humans
with 10% to 15% of their caloric requirement [34]. Lactobacillus species are responsible for a significant proportion
of bile acid deconjugation, a process that efficiently reduces
lipid absorption in the gut [35].
Mice that are genetically obese (ob/ob) have 50% fewer
Bacteroidetes (and correspondingly more Firmicutes) than
their lean (+/+) siblings [36•]. Other animal studies have
confi rmed that gut microbiota in these ob/ob mice are
more effective at releasing calories from food during digestion than are the +/+ microbiota. Most importantly, this
trait is transmissible: colonization of germ-free mice with
an “obese microbiota” results in a significantly greater
increase in total body fat than colonization with a “lean
microbiota”[37••]. Germ-free mice are protected against
the obesity that develops after consuming a Westernstyle, high-fat, sugar-rich diet [38].
As in animal models, two groups of beneficial bacteria,
the Bacteroidetes and the Firmicutes, are also dominant in
the human gut. Ley et al. [39••] recently studied 12 obese
patients randomized to either carbohydrate-restricted or
fat-restricted diets and monitored them over the course of
1 year by sequencing 16S rRNA genes from stool samples.
The relative proportion of Bacteroidetes was lower in obese
people than in lean people, and this proportion increased
with weight loss.
Several mechanisms determine how the microbiome
influences the host. Peroxisome proliferator-activated receptor (PPAR)- γ, an intranuclear receptor highly expressed
in adipose tissue, is linked with insulin resistance.
B. thetaiotaomicron attenuates proinflammatory cytokine
expression by promoting nuclear export of the NF-κ B subunit RelA through a PPAR- γ –dependent pathway in Caco-2
cells exposed to Salmonella enteritidis [40]. The role of
the microbiome has therefore been further investigated by
metabonomic studies. In addition to the suppression of the
inflammatory response and the regulation of fat storage by
microbiota [41], a diet-induced mechanism of steatosis triggered by symbiotic microbiota has been described [42•].
Nonalcoholic fatty liver disease (NAFLD) was induced in
mice given a high-fat diet. They demonstrated low plasma
phosphatidylcholine concentrations and high levels of
urinary methylamines as detected by 1H NMR. Methylamines are coprocessed by gut microbiota, resulting in the
observed reduction of choline bioavailability and NAFLD.
Hierarchical metabonomic clustering derived from 1H
NMR plasma spectral data in a mouse model has also provided a phylometabonomic classification of strain-specific
metabolic features and differential responses to a high-fat
diet that closely match SNP-based phylogenetic relationships among strains [43].
The microbiome also influences the host obesity
phenotype via the gut-brain axis. There is evidence
that the intestinal flora or dietary components trigger
the production of autoantibodies that cross-react with
regulatory peptides via a mechanism of molecular
mimicry [44]. Germ-free rats maintain relatively lower
levels of IgA autoantibodies directed against hormones
(eg, corticotropin-releasing hormone) because of the
absence of intestinal antigens. However, in the presence of selected pathologic flora, the production of IgG
autoantibodies directed against ghrelin is upregulated,
suggesting a complex mechanism of interaction between
microbial antigens and autoantibody levels. Peptide fragments identical to leptin were found in proteins belonging
to Lactococcus lactis, Escherichia coli, Lactobacillus
bacteriophage, Yarrowia lipolytica, and Candida and
Aspergillus species. Sequence homology was also demonstrated in Lactobacilli and their phages, Bacteroides, and
commensal strains of E. coli, which displayed molecular mimicry with leptin, insulin, ghrelin, and other
hormones. It is therefore possible that under normal conditions, not a single regulatory peptide may escape this
microbe-derived, immune-mediated control.
Hypertension and cardiovascular risk
The International Study of Macronutrients and Blood Pressure (INTERMAP) used a 1H NMR–based metabonomic
approach to investigate differences in urine metabolic
profiles across 17 large populations, with 4630 participants from China, Japan, the United Kingdom, and the
United States [45]. It demonstrated that urinary metabolite
excretion patterns for East Asian and Western population
samples are significantly different, as are patterns for subgroups with differences in blood pressure and in dietary
intake of vegetable/animal protein [46]. Increased levels
of formate, a microbial co-metabolite, were significantly
associated with higher blood pressure in multiple regression analyses, as were high alanine and low hippurate. The
implication is that this technology can now be employed
to study the metabolic perturbations effected by the
microbiome that are associated with geographic variations
commonly found in numerous diseases.
The Human Gut Microbiome: Implications for Future Health Care Kinross et al.
Future Implications of Research on Gut
Microbiome Activity
The concept of “bioecologic” control of the gut has
recently been proposed as a novel method of improving
human health [47 ]. This approach encompasses the use of
“functional foods”—probiotics, prebiotics (nondigestible
food ingredients that benefit the host by selectively stimulating the growth or activity of bacteria that can improve
the host’s health), and synbiotics (a combination of both)
[48]. There is now considerable evidence to support the
efficacy of this approach, with numerous studies suggesting that functional foods improve outcome in IBS, IBD
[49], and antibiotic-associated diarrhea in the critically
ill. However, the mechanisms by which prebiotic bioecologic strategies exert their beneficial health effects remain
largely unknown. Furthermore, considering the large variability in the human intestinal ecosystem, these approaches
are unlikely to fulfill their potential until it is possible to
determine the exact profile of an individual’s microbiome.
Then specific biologic treatments can be tailored to an individual’s need. The result may be the development of novel
therapeutic strategies for systemic conditions not typically
associated with the gut, such as diabetes or cardiovascular
disease. Patterns of gut microbiota, as well as specific bacterial species, that are associated with certain diseases will
also constitute a new type of drug target [11•].
It is also feasible that intestinal flora will be used
not only as a novel method of drug delivery but also as
a bioreactor, using new cloning and biosynthetic expression strategies for the controlled secretion of biologically
active molecules and vaccines. A new class of pharmaceutical compounds derived from previously uncultured
commensal microorganisms in appropriate in vitro or
animal models may be produced to develop long-term host
immunotherapy for diseases such as IBD [11•].
Although animal studies are useful for indicating possible mechanisms of action, functional foods will be accepted
in mainstream therapy only when a clear mechanistic
link is established between microbiotal modulation and
improvements in host health or biomarkers of disease risk.
Animal gut flora may not accurately reflect human flora.
However, encouraging first steps are being made through
the development of a germ-free mouse model that is colonized with human baby flora [14], as well as germ-free
piglets transfected with human flora, which demonstrate
minimal individual variation and aging patterns similar to
those observed in humans [50].
Conclusions
Metagenomic and metabonomic approaches are beginning to provide us with a greater understanding of
biologic function and the complex host-microfloral metabolic cross-talk of humans at a “superorganism” level.
These tools permit in-depth and noninvasive analysis of
intestinal ecology. The initial evidence provided by such
401
an approach suggests that the mammalian/microbiome
symbiosis is vital to human health and fundamental to
numerous pathologic processes. The notion that the intestine is instrumental in the development of many systemic
conditions not previously associated with the gut implies
that the role of the gastroenterologist is becoming increasingly important. These system-based approaches are also
likely to underpin disease prevention strategies, personalized health care regimens, and the development of novel
therapeutic approaches of the future.
Acknowledgment
James Kinross and Alexander von Roon are both funded
by One-year Surgical Research Fellowships granted by the
Royal College of Surgeons of England.
Disclosures
No potential conflicts of interest relevant to this article were reported.
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