Gastroenterology 2017;152:313–321
Understanding and Preventing the Global Increase of
Inflammatory Bowel Disease
Gilaad G. Kaplan1,2,* Siew C. Ng3,*
1
Department of Medicine, 2Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada;
3
Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases,
Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong, China
The inflammatory bowel diseases (IBDs) are contemporary
conditions of industrialized societies. The prevalence of
IBD continues to increase steadily in Western countries,
and newly industrialized countries have a rapidly
increasing incidence. The global spread of IBD appears to
associate with Westernization of diets and environments,
which affects the intestinal microbiome and increases the
risk of IBD in genetically susceptible individuals. It is
important to increase our understanding of these events to
slow progression of IBD. We present a long-term plan to
develop interventions that slow or stop the global increase
in the incidence of IBD.
Keywords: Crohn’s Disease; Ulcerative Colitis; Gene–
Environment Interaction; Microbiota.
T he evolution of the inflammatory bowel diseases
(IBDs) follows the advancement of society.1 System-
atic documentation of ulcerative colitis began in Western
Europe in the 1800s, with the first case report published by
Wilks and Moxon2 in 1859. The emergence of ulcerative
colitis in Western Europe paralleled the advent of the
industrial revolution in the 1800s, a time when approxi-
mately 1 billion people lived on earth.3 The industrial revo-
lution led to increased urbanization, with a shift in economies
from rural (agricultural) to urban (manufacturing). The
increasing population density within cities greatly changed
diet and lifestyles—today these societal changes are called
Westernization.4
The incidence of ulcerative colitis slowly increased in the
early 1900s in Western countries, and regional ileitis entered
the medical vernacular in 1932 after the publication of a
series of cases by Crohn et al.5 The 1950s was considered to
be the start of the great acceleration of human civilization,
denoted by exponential global growth in the human
population.6 The rapid population increase was driven by
economic advancement, automation, increased food
production, and profound resource and energy utilization.6
Likewise, the incidence of ulcerative colitis and Crohn’s dis-
ease exploded in wealthy Westernized countries during the
last 50 years of the 20th century (Figure 1).7 Many factors
contributed to the increase in the incidence of IBD, including
increased awareness, improved access to medical technology
and health care providers, development of sophisticated
disease surveillance systems, and environmental exposures
associated with Westernization of society.1
We define Westernized countries as high-income coun-
tries of dominantly Western European cultural heritage:
Western Europe, the United States, Canada, Australia, and
New Zealand. These countries have a shared industrial
history with the industrial revolution that began in Great
Britain in the 18th century before spreading to the rest of
Western Europe and to Western European colonies in North
America and Oceania. For brevity, we use the terms indus-
trializing and newly industrialized to describe countries that
are developing or have developed, respectively, qualities
similar to the wealthy Westernized countries and regions
(eg, industrialization, diet, health care, urbanization). We
also use the terms Western countries and industrialized
countries to refer to wealthy Westernized countries.
The end of the 20th century is recognized as the onset of
globalization whereby certain industrializing countries in
Asia, the Middle East, and South America became more
Westernized. During this time, newly industrialized coun-
tries experienced rapid population growth, urbanization,
industrialization, and Westernization of culture.8 In com-
parison with Western countries, the pace of these changes
was accelerated dramatically, even when compared with the
*Authors share co-first authorship.
Abbreviations used in this paper: IBD, inflammatory bowel disease; MAC,
microbiota-accessible carbohydrate.
Most current article
© 2017 by the AGA Institute
0016-5085/$36.00
http://dx.doi.org/10.1053/j.gastro.2016.10.020
314 Kaplan and Ng
Western Industrial Revolution. Nearly 100 years after Sir
Wilks case report of IBD,2 the first case of ulcerative colitis
was recognized in 1956 in China.9 Systematic analyses
confirmed that the incidence of ulcerative colitis, followed
by that of Crohn’s disease, was increasing in Asia at the turn
of the 21st century, similar to that observed in Western
countries during the 20th century (Figure 1).10
In 2017, IBD is a global disease with the highest prev-
alence in Western countries, but with newly industrialized
countries documenting the greatest increases in incidence.
The peak in the incidence of IBD in newly industrialized
countries is unknown. However, despite this, with popula-
tion sizes of countries such as India and China each
exceeding 1 billion, the future global impact of IBD simply
cannot be ignored. We review the global epidemiologic
features of IBD, discuss what these tell us about the path-
ogenesis of IBD, and recommend future directions for
research. Based on this information we will propose a
moonshot to cut the global incidence of IBD by 50%
by 2032.
Epidemiologic Features in 2017
The diagnosis of IBD is made in every inhabitable
continent, among all ethnicities and socioeconomic classes.
Although IBD is most prevalent among individuals of
European descent living in wealthy Western countries,
newly industrialized countries in Asia, the Middle East,
Africa, and South America have reported rapid increases in
incidence.10 As incidence increases, the prevalence of IBD
also is increasing in many of these countries. IBD care will
be required for an older population in the Western
countries and a younger population in newly industrialized
countries.1 This information is required to develop a global
strategy for handling the future burden of IBD.
Gastroenterology Vol. 152, No. 2
Figure 1. Increasing trend
of IBD in industrialized
countries since the 19th
century and in industrial-
izing countries since the
20th century. The interac-
tive global map of IBD inci-
dence and prevalence can
be found at: https://people.
ucalgary.ca/wggkaplan/IB
DG2016.html. UC, ulcera-
tive colitis.
Since 2000, the prevalence of IBD has ranged from 0.3%
to 0.5% in North America.11,12 Similar high prevalence
values have been reported in Northern Europe (eg, United
Kingdom and Scandinavia),13,14 Western Europe (eg, Spain
and Germany),15,16 and Oceania (eg, New Zealand).17 What
began as a handful of cases of ulcerative colitis, followed by
Crohn’s disease, in the early 1900s in Western countries has
grown to millions of individuals afflicted with IBD in North
America, Europe, and Oceania.18,19 The steady increase in
the prevalence of IBD coincided with the great acceleration
of the human population in the last half of the 20th century.6
During this time the incidence of Crohn’s disease and
ulcerative colitis sharply increased; a finding consistently
shown by more than 200 epidemiologic studies investi-
gating IBD in Western countries during the 20th century
(Figure 1).10
Since the start of the 21st century, the incidence of IBD
has been changing in Western countries. Some contempo-
rary population-based studies have shown stabilization, and
some have reported a decreasing incidence of IBD, although
pediatric-onset IBD continues to increase steadily in
incidence.11,20–22 Nonetheless, population-based studies of
Western countries have shown consistently that since 2000,
the incidence of IBD has not accelerated at the same rates
observed at the end of the 20th century. Despite the easing
of the incidence rates in some regions, the prevalence of IBD
continues to increase substantially throughout the world.10
IBD is a chronic disease with relatively low mortality
that is diagnosed primarily in young individuals. Conse-
quently, the prevalence of IBD increases over time such that
new diagnoses add to the base population at a rate signifi-
cantly higher than the loss of patients from a clinical prac-
tice. The net effect is a steady increase in the prevalence of
IBD over time. For example, in Olmsted County, Minnesota,
the prevalence of Crohn’s disease was only 28 cases per
January 2017
100,000 in 1965,23 increasing to 90.5 per 100,000 in
1980,24 132.7 per 100,000 in 1991,25 213.9 per 100,000 in
2001,26 and 246.7 per 100,000 in 2011.27
The increase in the prevalence of IBD in Western
countries poses a significant challenge to gastroenterolo-
gists. For example, the prevalence of IBD in the United
States was estimated to be slightly more than 0.5% in 2015,
and is forecasted to increase to more than 0.6% in a decade,
which equates to approximately 2.2 million Americans living
with IBD in 2025.28 Naturally, the average age of patients
with established IBD increases each year, which in turn af-
fects the complexity of care because older patients have
more comorbidities and complications. Over the next
decade, the number of patients with IBD may overwhelm
gastroenterology clinics, necessitating innovations in health
care delivery to meet the increasing demand.
In contrast, newly industrialized countries in Asia, the
Middle East, Africa, and South America have a low preva-
lence of IBD.10 Studies recording the prevalence of IBD in
newly industrialized countries are relatively sparse because
of a lack of infrastructure for routine population-based
disease surveillance. The prevalence of IBD in Japan was
76 cases per 100,000 in 2005,29 whereas in South Korea the
prevalence of IBD was 42 per 100,000,30 and the prevalence
in Hong Kong was 43 per 100,000 in 2014.31 Fortunately,
studies on the incidence of IBD in newly industrialized
countries are becoming more common because several
inception cohorts have been coordinated by gastroenterol-
ogists. The most noted inception cohort outside of Western
countries is the Asia–Pacific Crohn’s and Colitis Epidemio-
logic Study—a population-based cohort of newly diagnosed
patients with IBD (2011–2013) from 13 countries in the
Asia–Pacific region.32
The incidence of IBD in Asia is 1.4 cases per 100,000 and
climbing.32 The highest incidence of IBD among the Asia–
Pacific Crohn’s and Colitis Epidemiologic Study countries is in
India at 9.3 per 100,000 person-years.33 Overall, the inci-
dence of IBD in China is 3.3 per 100,000; however, variation is
high across China, with the highest incidence rates observed,
tellingly, in regions with the greatest urbanization and the
most economic advancement.33,34 In Asia, ulcerative colitis is
2-fold more likely to be diagnosed than Crohn’s disease,
although this ratio has been decreasing over time.32
The incidence of IBD also is increasing rapidly in newly
industrialized countries outside of Asia.10 For example, the
incidence of Crohn’s disease and ulcerative colitis substan-
tially increased in Piaui, Brazil, from 1988 to 2012.35
Furthermore, in Sao Paulo, Brazil, the incidence of IBD
doubled from 4.5 per 100,000 (1991–1995) to 9.7 per
100,000 (2001–2005).36 Data from Uruguay37 and
Barbados38 have shown patterns similar to those of Brazil,
indicating that the incidence of IBD is increasing in Central
and South America.
However, the greatest gap in our understanding of the
epidemiologic features of IBD comes from the lack of data
from most newly industrialized countries—especially from
developing nations. Our interactive global map of IBD
incidence and prevalence can be found at: https://people.
ucalgary.ca/wggkaplan/IBDG2016.html. In addition, see
Global Increase of IBD 315
the Supplementary Appendix for a static global map with an
accompanying table describing the incidence and preva-
lence by country.
The current incidence rates and prevalence values
reported from newly industrialized countries are akin to
rates published in Western countries in the 1970s and
1980s.10 If the increase of IBD in newly industrialized coun-
tries parallels those of Western countries 30–40 years ago,
then the global prevalence of IBD will climb steadily, affecting
tens of millions of people throughout the world over the next
generation. In 2027, newly industrialized countries almost
certainly will be caring for considerably more patients with
IBD, most diagnosed as they enter the work force. Young in-
dividuals with IBD living in poorer countries may face bar-
riers in access to care and their ability to afford costly drugs
such as biologics. The net effect is a global IBD community
with a wide variation in health outcomes, resulting not from
differences in disease pathogenesis but rather from economic
disparities. Increasing our understanding of the pathogenesis
of IBD with the goal of using our knowledge to prevent dis-
ease should be a top priority.
Genetic Clues to Pathogenesis
Pathogenesis of Crohn’s disease and ulcerative colitis
involves a dysregulated immune response to commensal
microbiota in genetically susceptible individuals. The life-
time risk of IBD in first-degree relatives is at least 2-fold
higher in Ashkenazi Jews than in non-Jews.39 Twin studies
have supported the heritable component of Crohn’s disease
and ulcerative colitis.40 Crohn’s disease has 20%–50%
concordance between monozygotic twins and 10% concor-
dance in dizygotic twins; concordance values for ulcerative
colitis are estimated to be lower, at 15% and 5%, respec-
tively. This observation indicates a weaker heritable
component for ulcerative colitis.41
In 2001, linkage analyses identified variants in the NOD2
gene (also called CARD15) that increased risk for Crohn’s
disease. This observation supported the model that alter-
ations in innate immunity and the immune response to bac-
teria contributed to the pathogenesis of Crohn’s disease.42–44
Since then, genome-wide association studies within genetics
consortia have identified more variants associated with
IBD.45 There are now more than 200 IBD risk loci, which
indicate the involvement of innate immune response, adap-
tive immunity, autophagy, endoplasmic reticulum stress, in-
testinal epithelial barrier function, and microbial defense
pathways in IBD.45–47 Furthermore, approximately 70% of
IBD risk loci are shared with other immune-mediated disor-
ders such as type 1 diabetes mellitus, celiac disease, rheu-
matoid arthritis, ankylosing spondylitis, and psoriasis.48
Genetic risk for IBD varies among different populations;
individuals of African-American and Asian ancestry have a
lower familial risk.49 A meta-analysis of genetic studies of
different ethnic groups13 found most IBD risk loci to be
shared among diverse ancestry groups (eg, African Ameri-
cans, Caucasians, and Asians). There were only a few
population-specific risk loci, with heterogeneity in effect
size (such as in TNF-SF15 and ATG16L) or risk-allele
316 Kaplan and Ng
frequency (such as in NOD2).47 This was reported in a
transethnic association study of Crohn’s disease and ulcer-
ative colitis, comprising 86,640 Europeans and 9846 in-
dividuals of East Asian, Iranian, and Indian descent, which
identified 38 new risk loci.47 Analyses of the functions of the
products of the genes at these loci associated risk of IBD, in
Western and Eastern populations, with an abnormal im-
mune response to gut microbes.
Genetic studies have greatly increased our understanding
of the pathogenesis of IBD. It is still not clear, however, why
most individuals who carry IBD-associated risk variants
remain healthy while others develop IBD or even develop
more than 1 immune-mediated disease. Epigenetic modifi-
cations are present in the fertilized egg and then every cell of
every tissue in an organism; they control gene expression
patterns and each cell’s response to environmental factors,
and thereby regulate the immune response and host control
of the microbiome.50 Increasing our understanding of in-
teractions among genetic, environmental, and microbial fac-
tors could provide insight into why only some people in
high-risk families, or persons with specific risk factors,
develop IBD (Figure 2).
Environmental Determinants
The increasing incidence of IBD in newly industrialized
countries indicates the influences of a Western lifestyle,
urbanization, and industrialization on risk.34,51 Empiric ob-
servations have shown a handful of environmental risk
factors for IBD,52 including cigarette smoking (protects
against ulcerative colitis in all regions; increases risk for
Crohn’s disease in Western, but not in Eastern Asian,
countries),51,53 antibiotic use during childhood (increases
risk in Western countries but reduces risk in Eastern Asian
countries and among immigrants from the Middle East),51,54
breastfeeding (protects against IBD in a dose-dependent
manner),55 oral contraceptives (increases risk for Crohn’s
disease),56 appendectomy (protects against ulcerative coli-
tis),57 low levels of vitamin D (increases risk for Crohn’s
disease),58 and consumption of tea or coffee (reduces risk
for Crohn’s disease and ulcerative colitis among Asians).59
The hygiene hypothesis, proposed by Strachan60 in the
19th century, provides an explanation for the increasing
incidence of autoimmune and allergic diseases in industri-
alized nations. Factors inversely associated with risk of
Crohn’s disease and ulcerative colitis include having pets in
childhood, living on a farm, having a larger family, and
drinking unpasteurized milk.61,62 The hygiene hypothesis,
however, may not apply to all populations worldwide. For
instance, in India, measures of low hygiene were associated
unexpectedly with an increased risk of ulcerative colitis.63
Sikh, Hindu, and Muslim migrants in the United Kingdom
have a higher risk of ulcerative colitis than nonmigrants.64
Antibiotic use has been shown consistently to be a risk
factor for IBD in Western countries, although a protective
effect for IBD was reported for Asians and Middle Eastern
migrants.52,59 This might be because childhood use of anti-
biotics in developing countries indicates exposure to infec-
tious agents. By contrast, antibiotic-induced dysbiosis may
Gastroenterology Vol. 152, No. 2
not develop as easily in developing countries, owing to
ubiquitous exposure to a diverse range of microbiota that
rapidly can repopulate the intestinal tract.65 To add another
level of complexity, microbe exposures change throughout
life, beginning before birth. The sheer number of microbes to
which each person is exposed, differences in host response to
microbes (based on genetic factors), and differences in timing
and duration of exposures complicate the search for microbes
that increase the risk of IBD (Figure 2).66
Diet
Specific dietary nutrients and metabolites, in combination
with genetic factors, affect the intestinal microbiota and affect
risk of inflammation. Transition of populations from rural
regions to urban cities often is accompanied by greater food
abundance, physical inactivity, and psychosocial stress. One
such example is the marked difference of nutrition and health
status between rural and urban populations in China.67
The increasing incidence of IBD in Europe and the United
States since the 1950s, and in Asia in the early 1990s, coin-
cided with the introduction and promotion of packaged food
and fast food chains, as well as increased use of antibiotics in
human beings and livestock.68 Consumption of fat, refined
sugar, and processed food has increased worldwide over the
past 3 decades in developed and undeveloped countries.
Several macronutrients have been associated consistently
with IBD risk. Dietary fiber reduces risk,69,70 whereas dietary
fat, animal protein, and sugar increase risk.52,71–73 A study in
Sweden associated consumption of fast food with an
increased incidence of ulcerative colitis.74 Differences in
exposure to dietary components may account for geographic
variations in the incidence of Crohn’s disease in France.
Northern France has a diet rich in beer, butter, eggs, and
potatoes, whereas Southern France has a Mediterranean diet,
which includes many vegetables, fruits, fish, olive oil, and
wine, and has been associated with a reduced risk of IBD.75,76
However, it may not be the type of food, but the processing
of food that promotes intestinal inflammation. Studies in
animal models have shown that food additives, such as
saccharin and sucralose, can increase the risk of diabetes,
ulcerative colitis, and obesity.77 In predisposed mice,
carboxymethylcellulose and polysorbate-80, common emul-
sifiers in most food, induced low-grade gut inflammation and
colitis.78 Emulsifiers in concentrations found in human foods
change the microbiota composition and destroy the mucus
layer, allowing microbiota to encroach on the epithelium.
However, there are no corroborating data on the effect of food
additives in human beings. Several studies have associated
regular consumption of fast food with a risk of Crohn’s dis-
ease and ulcerative colitis. This could be related directly to
high levels of monounsaturated and polyunsaturated fatty
acids, or related indirectly to the less-active lifestyle of people
who consume fast food (Figure 2).79,80
The Microbiome and Epidemiology
The intestinal microbiome has an important role in IBD
pathogenesis.81,82 Patients with IBD have broad changes in
their intestinal microbiota profile compared with
January 2017 Global Increase of IBD 317

Figure 2. The genetic, environmental, and microbial determinants of IBD. CD, Crohn’s disease; UC, ulcerative colitis.

individuals without IBD. In addition, a number of specific
changes have been identified, such as a decrease of the
butyrate-producing species Roseburia hominis and Faecali-
bacterium prausnitzii.83 The commensal gut microbiota is
ecologically and functionally perturbed in patients with IBD.
Treatment-naive patients with new-onset Crohn’s disease
have been reported to have increased intestinal abundance
of Enterobacteriaceae and reductions in Clades IV and XIVa
Clostridia during disease-associated inflammation.84 Meta-
genomic studies and microarray analyses of Western pop-
ulations, and limited data from Asia, have reported
reductions of Firmicutes, such as F prausnitzii, and increases
in Escherichia coli, Fusobacterium, and Proteus, in patients
with IBD (Figure 2).81,82,85–87
318 Kaplan and Ng
Specific pathogens have been proposed to affect the
development of IBD. For example, as many as one third of
patients with Crohn’s disease have increased numbers of
mucosa-associated, adherent-invasive E coli in ileal tis-
sues.88 In addition, the lower prevalence of helminths in
industrialized societies have been proposed to increase the
risk of IBD.89 However, small studies of the whipworm
Trichuris suis ova in patients with Crohn’s disease produced
meaningful changes in symptoms.90 A meta-analysis asso-
ciated Mycobaterium avium paratubercolosis with Crohn’s
disease, although it is not clear how this microbe could
promote disease development.91
It is unclear if the changes in putative pathogens or
protective organisms identified in Western populations,
such as E coli and F prausnitzii, are more widespread in
regions of increased IBD incidence. Information also is
lacking about the degree of genetic variation between the
bacteria assigned to these taxonomic groups from different
ethnic and geographic regions.92
Variation in the composition of the intestinal microbiota
among individuals is greater in young children; infants have
the highest susceptibility to microbial change in response to
environmental factors.93 Microbial exposures during early
life affect the development of the immune system and
tolerance to environmental factors; this could contribute to
risk of IBD in later life.94 In the United States, an overall
decrease in microbiota diversity occurred simultaneously
with improved sanitation (filtered drinking water and early
use of antibiotics).95 Furthermore, effects of the environ-
mental factors on the microbiome, including antibiotic and
dietary exposures, could be cumulative across several gen-
erations.96 The liberal use of antibiotics in developed and
developing regions has been associated with marked de-
creases in 2 species from the genus Bifidobacterium.97
Microbiota-accessible carbohydrates (MACs) are abun-
dant in dietary fiber and serve as a source of energy for gut
microbiota. Mice fed a low-MAC diet, over several genera-
tions, had progressive loss of microbial diversity, which was
irreversible even after the reintroduction of MACs.96
Therefore, taxa driven to low abundance by lack of MACs
are at risk of becoming extinct.
Features of a Western diet, including higher consump-
tion of total energy, snacking, high-fat milk, and sugar-
sweetened soda, all were associated with a lower
microbiota diversity. By contrast, the intake of coffee, tea,
and red wine (with a high polyphenol content) were asso-
ciated with increased microbial diversity. Total carbohy-
drate intake was associated positively with Bifidobacteria,
but associated negatively with Lactobacillus, Streptococcus,
and Roseburia species.98 These findings support the
importance of interactions among environmental, dietary,
microbial, and host factors.99 Consumption of a modern diet,
low in fiber, contributes to loss of taxa over generations and
may be responsible for the lower-diversity microbiota
observed in industrialized countries compared with indus-
trializing countries. Soluble fiber not only helps maintain the
integrity of the epithelial barrier via decreased translocation
of E coli across Peyer’s patches in vitro,100 but also is
metabolized by the intestinal bacteria into short-chain fatty
Gastroenterology Vol. 152, No. 2
acids, which inhibit transcription of inflammatory cytokines
(Figure 2).101
Future Directions
The combination of the increasing prevalence of IBD
and high per-patient cost of care will strain nations and
widen the health care gap among individuals of different
socioeconomic status.1 Gastroenterologists must unite to
support a philosophy of clinical stewardship that balances
quality of care to patients with IBD and the increasing so-
cietal cost that jeopardizes this care. Gastroenterology
clinics therefore should innovate delivery of health care to
patients with IBD, to efficiently and equitably manage their
increasing number. The gastroenterology academic com-
munity therefore should prioritize research that addresses
its fundamental challenge: the global increase in the prev-
alence of IBD.
Innovations in Health Care Delivery
Over the next decade, the prevalence and economic
impact of IBD will increase exponentially, adding a greater
stress to a system already struggling with unequitable var-
iations in care and inefficient access. Addressing this chal-
lenge requires data from clinical practice. In 2014, the
Crohn’s and Colitis Foundation of America published a
policy position statement supporting “surveillance of the
burden of disease,” which integrates information on IBD
progression, outcomes, and complications of treatment.102
Several regions have developed sophisticated disease sur-
veillance systems that use administrative health care data-
bases or electronic medical records to assess disease
burden, including incidence and prevalence, along with
health care utilization such as hospitalization rates, medical
management, surgery, and costs. Most of these systems are
population-based with broad geographic coverage; they
capture information on care ranging from urban to rural
areas, as well as between community and academic prac-
tices. These systems will be critical in tracking disease
outcomes over time, particularly as new interventions
innovate the care of IBD. The next step, however, will be to
adopt these systems in newly industrialized countries.7
Table 1 presents potential innovations for health care de-
livery to the IBD community and the priority on research.
Preventing the Global Increase
To stop the global increase of the incidence of IBD, we
should direct our attention to factors associated with pro-
tection. Because potentially relevant environmental in-
fluences span the spectrum from mode of birth, to early life
exposures, to risk factors in adulthood, different populations
with different risk factors may require interventions at
different time points. Several groups are potentially the
most useful to study: pediatric populations, high-risk groups
(first-degree relatives and multiplex families), and pop-
ulations with rapidly increasing incidence.
The complex and poorly understood interactions among
genetic and environmental factors influencing the risk of
January 2017
Table 1.Innovations for Delivery of Health Care to Patients
With IBD
Personalized medicine Clinicians have numerous options within
and across classes of biologics to treat
patients with IBD. The choice of agent,
dose, duration, and timing of introduction
should not be arbitrarily based, but be
guided by biomarkers derived through
knowledge of pathogenesis. Treating
an individual with precision will optimize
the use of biologics, reduce waste,
and minimize toxicity.
Electronic health care Electronic systems have revolutionized
the way patients and physicians interact.
Electronic portals that connect patients
to their records will allow patients to
participate actively in their care. Mobile
devices and health care applications
allow physicians to monitor patients
remotely. Centralized electronic
referrals could standardize the referral
process, improve access to specialists,
and use algorithms to identify and
triage patients with undiagnosed IBD.
The urban–rural divide Access to timely and appropriate care
can be a challenge for patients living
in rural areas. This challenge will be
especially heightened in newly
industrialized countries where resources
and infrastructure outside of metropolitan
cities may be limited. Telehealth clinics
can facilitate communication between
patients, primary care physicians, and
gastroenterologists.
Clinical care pathways The IBD community has developed
numerous clinical care guidelines
and pathways that direct management.
The next step is to develop integrative
clinical care pathways that can be
used by primary care physicians and
nurse practitioners specializing in
IBD to offset the management of
a subgroup of patients with controlled
disease activity.
developing Crohn’s disease and ulcerative colitis pose
challenges to developing new strategies to prevent and treat
IBD. Nonetheless, several environmental factors can be
targeted to reduce the incidence of IBD. First, cigarette
smoking increases the risk of Crohn’s disease whereas
quitting smoking increases the risk of ulcerative colitis.53
Preventing smoking among adolescents could have the
largest impact in reducing the incidence of IBD. The pro-
tective effect of breastfeeding in IBD, as well as other
autoimmune and allergic disorders, also has been estab-
lished.103 Breastfeeding, and duration of breastfeeding, de-
creases with industrialization and modernization, but could
be increased by health professionals raising awareness in
new parents. A diet high in fiber protects against Crohn’s
disease.69 Unfortunately, most individuals on Western diets
do not achieve even the minimum recommended daily
intake of fiber.104 Use of antibiotics during the first few
Global Increase of IBD 319
years of life appears to increase the risk of IBD among
persons in Western countries.54 Judicious use of antibiotics
in children may reduce the incidence of IBD. Vitamin D
supplementation may be a simple mechanism to reduce IBD
incidence, particularly in Northern countries where there is
widespread vitamin D deficiency.34
However, there have not been interventional studies to
support associations between environmental factors and
IBD risk. It is difficult to show that modifying an exposure
prevents the development of IBD. Research therefore should
move away from solely identifying risk factors to showing
that specific interventions reduce, or do not reduce, the
incidence of IBD.
Reducing Incidence by Half by 2032
We are far from preventing IBD or even reducing its
increase in incidence. However, with advances in our
knowledge of IBD pathogenesis and genetics, and the effects
of the microbiome and environmental factors on risk, the
IBD community should prioritize a moonshot to cut the
global incidence of IBD in half by 2032—the 100th anni-
versary of the discovery of Crohn’s disease. A moonshot idea
proposes an innovative solution to a fundamental challenge
using revolutionary technology. Our fundamental challenge
is to reduce the incidence of IBD, to allow countries to
manage the increasing prevalence of IBD. For newly
industrialized countries, reducing incidence now will pre-
vent prevalence values from reaching those of Western
countries.
We can use new technologies to perform cost- and time-
efficient analyses of the microbiome, coupled with advances
in computational analytic approaches, to define the
composition, diversity, and function of a microbiome that
protects against IBD. Microbiome analyses could identify
individuals at risk, at all stages of life, and lead to strategies
to manipulate the microbiome to reduce this risk. Screening
of at-risk neonates’ or infants’ microbiomes could identify
those most likely to develop IBD. Personalized diets devised
to alter microbiota composition and functions, individual-
ized probiotics and prebiotics, and microbiome-modulated
metabolites that alter interactions between the immune
system and the microbiota all could be developed to reduce
IBD risk or slow its development.
Supplementary Material
Note: The first 50 references associated with this article are
available below in print. The remaining references accom-
panying this article are available online only with the elec-
tronic version of the article. To access the supplementary
material accompanying this article, visit the online version
of Gastroenterology at www.gastrojournal.org, and at http://
dx.doi.org/10.1053/j.gastro.2016.10.020.
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Received July 11, 2016. Accepted October 20, 2016.
Reprint requests
Address requests for reprints to: Gilaad Kaplan, MD, MPH, FRCPC, Teaching
Research and Wellness Center, 3280 Hospital Drive NW, 6D56, Calgary,
Alberta, T2N 4Z6 Canada. e-mail: ggkaplan@ucalgary.ca; fax: (403) 592-
5090; or Siew C. Ng, MBBS, FRCP (Lond, Edin), PhD (Lond), FHKCP,
FHKAM (med), Department of Medicine and Therapeutics, Chinese University
of Hong Kong, Hong Kong. e-mail: siewchienng@cuhk.edu.hk; fax: (852)
2637-3852.
Acknowledgements
The authors would like to thank Fox Underwood for editing the manuscript and
creating the interactive map. The geographic country data were created by the
Natural Earth community,105 and the world map was prepared using QGIS106
with the HTML Image Map Plugin.107 The authors would like to thank
Whitney Tang and Tiffany daVanzo for their assistance in the development of
the figures.
Conflicts of interest
The authors disclose no conflicts.
321.e1 Kaplan and Ng
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