review
org
Post-infectious irritable bowel syndrome following
water contamination
John K. Marshall1
1
Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Post-infectious irritable bowel syndrome (PI-IBS) is a common
disorder wherein symptoms of IBS begin after an episode of
acute gastroenteritis. The Walkerton Health Study (WHS) was
initiated in 2002 to study the long-term outcomes of tragic
contamination of its municipal water supply with Escherichia
coli and Campylobacter species in 2000. Within a cohort of
2069 adult Walkerton residents with no prior history of
chronic gastrointestinal disorders, the incidence of PI-IBS
2 years after the outbreak was 10.1% among subjects with no
acute gastroenteritis vs 36.2% among those with clinically
suspected gastroenteritis (Po0.001). Long-term follow-up of
the WHS cohort has shown PI-IBS to have a favorable
prognosis, with spontaneous remission in most patients.
A recent meta-analysis of nine cohort studies estimated the
pooled odds ratio for developing IBS after enteric infection to
be 5.86 (95% CI 3.60–9.54). Risk factors for PI-IBS include
female gender, younger age, more severe acute enteric
infection, and psychiatric comorbidity. A prevailing
hypothesis is that PI-IBS results from a failure to
downregulate inflammation after an acute insult from
gastroenteritis, a model supported by preliminary studies of
intestinal permeability and pro-inflammatory genotypes.
Ongoing research is testing the hypothesis that PI-IBS
denotes increased susceptibility to more overt inflammatory
disorders such as Crohn’s disease. Although the Walkerton
outbreak of acute gastroenteritis was an awful human
tragedy, it is hoped that the WHS will advance our
understanding of PI-IBS and improve the outcomes of people
who suffer similar tragedies in the future.
Kidney International (2009) 75 (Suppl 112), S42–S43; doi:10.1038/ki.2008.618
KEYWORDS: post-infectious irritable bowel syndrome; water contamination;
acute gastroenteritis; E. coli O157:H7; intestinal permeability; outbreak
Correspondence: John K. Marshall, Division of Gastroenterology (2F59),
Department of Medicine, McMaster University Medical Centre, 1200 Main
Street West, Hamilton, Ontario, Canada L8N 3Z5.
E-mail: marshllj@mcmaster.ca
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http://www.kidney-international.
& 2009 International Society of Nephrology
Irritable bowel syndrome (IBS) is a common clinical disorder
that affects between 10 and 20% of people worldwide.1 IBS is
characterized by recurrent abdominal discomfort and altered
defecation in the absence of any measurable change in
intestinal structure or function. The Rome III criteria are the
most recent iteration of symptom classifications that
formalize the diagnosis of IBS.2 However, these criteria have
proven to be of greater value in defining homogeneous
patient groups for clinical research than for making diagnoses
and directing management in clinical practice.
Between 3 and 30% of people with IBS report that their
symptoms began after an episode of acute gastroenteritis.3
This phenomenon of ‘post-infectious’ IBS (PI-IBS) was first
reported over 50 years ago.4 PI-IBS remains of particular
interest to clinicians because it represents the only variant of
IBS with a defined point of onset. As such, PI-IBS is studied
to provide insight into the natural history and pathogenesis
of sporadic IBS. Despite such interest and the frequency with
which PI-IBS is encountered in clinical practice, its natural
history, epidemiology, and pathogenesis remain poorly
understood.
In May 2000, the contamination of the municipal water
supply of Walkerton, Ontario, led to B2300 cases of acute
gastroenteritis, 27 known cases of the hemolytic-uremic
syndrome, and six deaths.5 This unfortunate tragedy has
provided a unique opportunity to learn more about PI-IBS
and other sequelae of acute gastroenteritis. The Walkerton
Health Study (WHS) was initiated in 2002, both to study the
long-term health outcomes of water contamination and to
facilitate local residents’ access to health care.
From the 4315 people who enrolled in the WHS during its
first year of operation, a study cohort of 2069 adult
Walkerton residents with no prior history of IBS or other
chronic gastrointestinal disorders was constructed to study
the epidemiology and natural history of PI-IBS. Within this
cohort, exposure to acute gastroenteritis was defined as either
‘self-reported,’ with increased stool frequency, or ‘clinically
suspected,’ with documented health care contact during
the outbreak for acute symptoms. The incidence of PI-IBS
2–3 years after the outbreak was 10.1% among 701 subjects
with no acute gastroenteritis vs 27.5% among 904 subjects
with self-reported gastroenteritis and 36.2% among 464
subjects with clinically suspected gastroenteritis (P for all
Kidney International (2009) 75 (Suppl 112), S42–S43
JK Marshall: Post-infectious IBS
comparisons o0.001).6 PI-IBS was more likely than sporadic
IBS to exhibit a diarrhea-predominant pattern.
In a meta-analysis of nine cohort studies, the pooled odds
ratio for developing IBS after enteric infection was 5.86 (95%
CI 3.60–9.54).7 PI-IBS has been associated with female
gender, younger age, more severe acute enteric infection, and
psychiatric comorbidity.7,8 The nature of the inciting
pathogen may also be important. In a cohort study of 197
delegates to the 2002 meeting of the Canadian Society of
Gastroenterology Nurses and Associates who were exposed to
Norwalk-like viral gastroenteritis, PI-IBS appeared to be
common but short-lived.9
Most patients who develop PI-IBS are keen to learn their
prognosis, but few data have been available to answer their
questions. For example, Neal et al.10 reported that 6 of 14
subjects with PI-IBS recovered after 6 years and that recovery
was impaired by psychological comorbidity. The larger WHS
has provided more precise estimates of prognosis. Among
228 adults who suffered from acute gastroenteritis and had
IBS when assessed 2 years later, the proportion with
persisting IBS was only 53% after 4 years and 38% after
6 years.11 Hence, it appears that PI-IBS has a favorable
prognosis and resolves spontaneously in most patients.
The pathogenesis of PI-IBS remains unclear, but a number
of mechanisms have been proposed, including bile-salt
malabsorption, changes in serotonin expression, chronic
inflammation, and increased intestinal permeability. The
latter was confirmed in a study of 218 WHS participants who
underwent lactulose–mannitol permeability testing. In this
assay, the ratio of fractional urinary excretions of lactulose
and mannitol is measured following oral ingestion to
estimate the relative rates of paracellular vs transcellular
absorption. Using a ratio threshold of 0.020, intestinal
permeability was found to be increased among WHS
participants with IBS (35.6 vs 18.6%, P ¼ 0.007).12 Increased
intestinal permeability despite recovery from acute infection
might contribute to chronic mucosal inflammation from
increased exposure to luminal antigens.
A prevailing hypothesis is that PI-IBS results from a failure
to downregulate inflammation after an acute insult from
gastroenteritis. Indeed, earlier studies have linked IBS to
pro-inflammatory genotypes. In a preliminary genetic
analysis of 1117 subjects from the WHS cohort that had
suffered acute gastroenteritis, development of PI-IBS was
associated with polymorphisms related to innate immunity
(toll-like receptor 9 and interleukin 6) and epithelial
integrity (E-cadherin) in univariate analyses.13 This
exciting observation is consistent with models of altered
permeability and mucosal immune activation in the
pathogenesis of IBS. However, a more detailed study of these
genes is going on.
Inflammatory bowel disease (IBD) is a chronic disorder of
the gastrointestinal tract that manifests as two distinct
conditions, Crohn’s disease and ulcerative colitis. Similar to
PI-IBS, Crohn’s disease is thought to result from a
hyperactive immune response to luminal antigens and has
Kidney International (2009) 75 (Suppl 112), S42–S43
review
been associated with changes in intestinal permeability.14
Indeed, the analysis of a UK primary care database has
suggested that the incidence of Crohn’s disease also rises after
acute gastroenteritis.15 It has been proposed that the
development of PI-IBS might identify individuals at
increased risk of IBD, much like gestational diabetes might
identify women at increased risk of type II diabetes mellitus.
Accordingly, the epidemiology of IBD is being studied
carefully in the WHS cohort. It will be of great interest to
determine whether there are genetic or mechanistic links
among acute gastroenteritis, PI-IBS, and IBD.
The Walkerton outbreak of acute gastroenteritis was an
awful human tragedy. Although nothing can remedy the
suffering and loss experienced by local residents, their
contribution has allowed our understanding of the patho-
genesis of both IBS and IBD to advance. Ultimately, it is
hoped that an improved knowledge and understanding of
PI-IBS might improve the outcomes of others who suffer
similar tragedies in the future.
DISCLOSURE
The author has declared no financial interests.
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