J Neurogastroenterol Motil 2025; 31(1): 110-118  https://doi.org/10.5056/jnm24018
Incidence and Clinical Course of Post-infectious Irritable Bowel Syndrome in Patients Admitted to University Hospitals: 1-year Prospective Follow-up Study
Jae Gon Lee,1,2 Sang Pyo Lee, 2,3* Hyun Joo Jang,1,2 Sea Hyub Kae,1,2 Woon Geon Shin,2,4 Seung In Seo,2,4 Hyun Lim,2,5 Ho Suk Kang,2,5 Jae Seung Soh,2,5 Chang Seok Bang,2,6 Young Joo Yang,2,6 Gwang Ho Baik,2,6 Jin Bae Kim,2,7 Yu Jin Kim,2,7 and Chang Kyo Oh2,7; Hallym Gastrointestinal Study Group
1Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea; 2Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea; 3Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea; 4Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea; 5Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea; 6Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea; and 7Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
Correspondence to: *Sang Pyo Lee, MD, PhD
Division of Gastroenterology, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea
Tel: +82-2-2290-8343, E-mail: ultra_pyo@hanmail.net
Received: January 28, 2024; Revised: March 26, 2024; Accepted: April 10, 2024; Published online: December 18, 2024
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
Post-infectious irritable bowel syndrome (PI-IBS) is characterized by chronic gastrointestinal symptoms that arise following an episode of infectious enteritis. The incidence rates vary, ranging from 5% to 32% and the risk factors are not well known. We aim to investigate the incidence and risk factors of PI-IBS in enteritis patients admitted to university hospitals in Korea.
Methods
This multi-center prospective study was conducted in patients hospitalized for infectious enteritis. Each patient underwent 1 outpatient visit and 3 telephone surveys during the first year after discharge to determine if PI-IBS occurred within the follow-up period.
Results
In the 3-month survey, 7 out of 354 patients (2%) were diagnosed with PI-IBS, and after 1 year, only 1 patient met the criteria for IBS. No statistically significant difference was found between the PI-IBS group and the non-PI-IBS group in terms of age, sex, underlying diseases, medication history, gastrointestinal symptoms, enteritis location, causative strain, hospitalization and treatment periods, and laboratory findings. Female sex (P = 0.003), enteropathogenic Escherichia coli (EPEC) infection (P = 0.044), and a longer total treatment period (P = 0.018) were independent risk factors for diarrhea lasting ≥ 3 months after enteritis.
Conclusions
The incidence of PI-IBS in Korea was relatively low, and most cases improved over time. No risk factors associated with the development of PI-IBS were found. However, persistent diarrhea after enteritis was associated with female sex, EPEC infection, and severe or long-lasting enteritis. IBS symptoms may persist after severe enteritis but usually improve with time.
Keywords: Enteritis; Irritable bowel syndrome; Rome IV criteria
Introduction

Irritable bowel syndrome (IBS) is an intestinal-brain interaction disorder characterized by chronic abdominal pain and bowel movement disorders with no apparent organic cause.1 With a worldwide prevalence of 4.1% according to the Rome IV criteria, various physiological mechanisms have been proposed to contribute to the development of IBS, including alterations in the gut microbiome and interactions between the central, autonomic, and enteric nervous systems.2

Although the exact etiology of IBS remains elusive, evidence suggests that a previous gastrointestinal infection can cause IBS symptoms.3 While the acute symptoms of infectious enteritis are well-known and typically resolve within a short period, a proportion of patients may experience persistent gastrointestinal symptoms long after the resolution of the initial infection. This condition, termed post-infectious irritable bowel syndrome (PI-IBS), has gained increasing recognition in recent years due to its impact on the patients quality of life and healthcare resources.4

PI-IBS is characterized by a cluster of chronic gastrointestinal symptoms that arise following an episode of infectious enteritis.3,4 These symptoms often include abdominal pain, altered bowel habits (such as diarrhea, constipation, or both), bloating, and increased sensitivity to abdominal distension. PI-IBS can manifest with varying degrees of severity and duration, significantly impairing patients daily functioning and overall well-being.5

Extensive research has been conducted to elucidate the pathophysiological mechanisms underlying PI-IBS. It is believed that the initial gastrointestinal infection triggers an aberrant immune response and disrupts the intestinal microbiota, leading to persistent low-grade inflammation, altered gut motility, and visceral hypersensitivity.3,4,6 These multifactorial processes contribute to the development and perpetuation of the characteristic symptoms observed in PI-IBS patients. Several studies have explored the incidence and prevalence of PI-IBS in different populations, shedding light on its clinical significance. The reported incidence rates following infectious enteritis vary, ranging from 5% to 32% depending on the study population and follow-up duration.7-10 Several systematic reviews and meta-analyses reported an estimated incidence of approximately 10% or greater in individuals who experienced acute infectious enteritis.9,11,12 However, the incidence rates differ by geographic region, highlighting potential differences in host factors, pathogens involved, and genetic predispositions. These variations highlight the complex nature of PI-IBS and the need for further investigations better to understand its risk factors and potential preventive strategies.

The current study aims to investigate the incidence of PI-IBS in enteritis patients admitted to university hospitals in Korea. In addition, by investigating clinical features and underlying diseases, we wanted to determine the risk factors for the development of PI-IBS or equivalent symptoms.

Materials and Methods

Patients

This multi-center prospective study was performed from November 2019 to November 2023. Patients who were hospitalized for infectious enteritis for 3 years from November 2019 to November 2022 were recruited for this study. Each patient was followed up by phone survey for 1 year after discharge. The exclusion criteria were age less than 18 years or more than 90 years, patients who are unable to answer the telephone questionnaire properly (eg, foreign nationality, intellectual disability, etc), patients already diagnosed with IBS before enteritis, patients taking analgesics or antidepressants, accompanying intestinal disease (inflammatory bowel disease, tuberculous colitis, radiation colitis, ischemic colitis, Behcet’s disease, and eosinophilic enterocolitis), diagnosis of gastrointestinal cancer, abdominal surgery after discharge, and patients who refused to sign the consent form (Figure).

Figure 1. Schematic diagram of the study protocol. IBS, irritable bowel syndrome.

This study was conducted simultaneously in 5 Hallym University Medical Center hospitals (Gangnam Sacred Heart, Gangdong Sacred Heart, Dongtan Sacred Heart, Chuncheon Sacred Heart, and Hallym University Sacred Heart). We followed up with enteritis patients who were hospitalized at the hospitals to see if PI-IBS developed within 1 year. We also investigated possible risk factors for PI-IBS development. The risk factors included the following: age, sex, underlying disease and medication history, smoking history, drinking history, blood culture test at the time of hospitalization, stool polymerase chain reaction test for gastrointestinal pathogens, length of hospital stay, fever duration, diarrhea period, abdominal cramps, weight loss, bloody stools, blood test results during hospitalization (C-reactive protein [CRP], white blood cell count, etc), and location of enteritis on CT (eg, small bowel enteritis, right colitis, left colitis, and pancolitis). Weight loss was defined as a reduction in body weight of 5% or more from baseline weight.

All subjects were admitted to general wards or intensive care units. Vital signs were checked, and blood tests were performed at appropriate intervals according to the doctors instructions. Fever was defined as a temperature of 37.8°C or higher as measured by a tympanic thermometer. The patients were discharged from the hospital when fever, diarrhea, hematochezia, vomiting, and abdominal pain improved, and oral intake was tolerable. The total treatment period was defined as the period during which the patient received medications as an inpatient and outpatient.

This study was approved by the Institutional Review Board (IRB) of Hallym University School of Medicine, which confirmed that the study was being conducted according to the ethical guidelines of the Helsinki Declaration (HDT2019-10-003-002). After IRB approval, this study was registered as Clinical Research Information Service (CRIS) ID: KCT0004426.

Phone Survey and Study Groups

Written consent was obtained from patients who were discharged with improved enteritis at the time of their first outpatient follow-up (between 3 and 14 days after discharge). At the time of the outpatient visit, the presence of IBS findings was checked once again according to the Rome IV criteria based on the patients symptoms 6 months before (symptoms for 6 months before hospitalization for enteritis). Consequently, subjects who met IBS criteria in the survey or who had a previous diagnosis of IBS were excluded from the study. Then, a survey was conducted by phone at 3, 6, and 12 months to determine if PI-IBS occurred within the follow-up period. The survey consisted of structured questions including items on the frequency of abdominal pain in the last 3 months, the association of abdominal pain with bowel movements, change in the frequency of bowel movements, and change in stool consistency. If the patient met the criteria for IBS at least once in the 3 surveys, they were classified into the PI-IBS group, and otherwise, they were classified into the non-PI-IBS group. If IBS had occurred, we checked its subtype (IBS with predominant constipation, IBS with predominant diarrhea [IBS-D], IBS with mixed bowel habits, and IBS unclassified) according to the Rome IV criteria.13

Depending on the patients circumstances, the scheduled date of the call was set between a week before and after the date calculated from the registration date. If the patient did not answer the phone on the scheduled phone survey date, they received calls at least 3 other times. If patients could not be reached for even 1 out of the 3 phone surveys, they were excluded from the analysis.

Statistical Methods

All statistical analyses were conducted using SPSS software, version 19.0 for Windows (IBM Corp, Armonk, NY, USA). Differences between groups were evaluated using the Student t test or Mann-Whitney U test for continuous data and the chi-squared test or Fishers exact test for categorical data. We used logistic regression analysis to estimate the odds ratio (OR) and 95% confidence interval (CI) of the risk factors that were independently associated with diarrhea lasting more than 3 months after enteritis. Continuous variables are expressed as standard deviations, whereas categorical variables are presented as frequencies (%). A P-value of less than 0.05 was considered statistically significant.

Results

Patients and Baseline Characteristics

The study enrolled 400 patients, and 46 patients dropped out because they did not properly respond to the telephone survey. Finally, this study included 354 patients, of which 198 (55.9%) were women. During the 1-year follow-up period, 7 out of 354 (2.0%) patients were diagnosed with PI-IBS, of which 5 were female. The mean age of the patients was 41.14 ± 16.03 years (range, 18-85 years) and 34.57 ± 16.59 years (range, 18-59 years) in the non-PI-IBS group and PI-IBS group, respectively. No statistically significant difference was found between the groups in terms of age, sex, underlying diseases, history of cancer, or medication history (Table 1).

Table 1 . Comparison of Baseline Characteristics in the Non–post-infectious Irritable Bowel Syndrome Group and Post-infectious Irritable Bowel Syndrome Group

VariablesNon–PI-IBS group
(n = 347)
PI-IBS group
(n = 7)
P-value
Age (yr)a41.14 ± 16.0334.57 ± 16.590.338
Age range (yr)18-8518-59
≥ 6058 (16.7)00.605
Female sex193 (55.6)5 (71.4)0.472
Past history of cancer9 (2.6)0 (0.0)> 0.999
Smoking0.609
Non-smoker272 (78.4)6 (85.7)
Past smoker30 (8.6)1 (14.3)
Current smoker45 (13.0)0 (0.0)
Alcohol0.197
Non-drinker179 (51.6)4 (57.1)
Social drinker157 (45.2)2 (28.6)
Heavy drinkerb11 (3.2)1 (14.3)
Comorbidity
Diabetes32 (9.2)1 (14.3)0.499
Hypertension44 (12.7)1 (14.3)> 0.999
Dyslipidemia9 (2.6)1 (14.3)0.183
Congestive heart disease4 (1.2)0 (0.0)> 0.999
Stroke2 (0.6)0 (0.0)> 0.999
Medication
Antiplatelet agent12 (3.5)0 (0.0)> 0.999
Anticoagulant2 (0.6)0 (0.0)> 0.999

aContinuous variables were summarized as mean ± SD and analyzed by the Mann-Whitney test. All other data were presented as n (%) and analyzed by the chi-square test and the Fisher’s exact test.

bHeavy drinking was defined as consuming 15 drinks or more per week for men and 8 drinks or more per week for women.

PI-IBS, post-infectious irritable bowel syndrome.



Clinical Features of Acute Gastroenteritis

Diarrhea, abdominal pain, fever, hematochezia, weight loss, and vomiting occurred in 335 (94.6%), 316 (89.3%), 255 (72.0%), 38 (10.7%), 80 (22.6%), and 95 (26.8%) patients, respectively. The most commonly identified pathogenic organism was Campylobacter (143 patients, 40.4%). No significant differences were found between the 2 groups in gastrointestinal symptoms, including abdominal pain, diarrhea, hematochezia, weight loss, vomiting, and fever (Table 2). In addition, no significant differences were found in the location of enteritis, causative strain, hospitalization period, total treatment period, and maximum body temperature, between the groups.

Table 2 . Comparison of Clinical Features of Acute Gastroenteritis in the Non–post-infectious Irritable Bowel Syndrome Group and Post-infectious Irritable Bowel Syndrome Group

VariablesNon–PI-IBS group (n = 347)PI-IBS group (n = 7)P-value
Location of enteritis on CT scan0.071
Pancolitis193 (55.6)3 (42.9)
Right colitis100 (28.8)2 (28.6)
Left colitis23 (6.6)0 (0.0)
Inflammation confined to the small bowel7 (2.0)2 (28.6)
No apparent inflammation on CT19 (5.5)0 (0.0)
CT scan not performed5 (1.4)0 (0.0)
Causative organism0.483
Aeromonas2 (0.6)0 (0.0)
Y. enterocolitica1 (0.3)0 (0.0)
Vibrio1 (0.3)0 (0.0)
Shigella3 (0.9)0 (0.0)
Escherichia coli20 (5.8)0 (0.0)
E. coil O157:H711 (3.2)0 (0.0)
Other STEC1 (0.3)0 (0.0)
EPEC5 (1.4)0 (0.0)
ETEC1 (0.3)0 (0.0)
EAEC2 (0.6)0 (0.0)
Enteric adenovirus1 (0.3)0 (0.0)
Astrovirus3 (0.9)0 (0.0)
Norovirus GI9 (2.6)0 (0.0)
Norovirus G24 (1.2)0 (0.0)
Campylobacter140 (40.3)3 (42.9)
C. perfringens10 (2.9)0 (0.0)
C. difficile10 (2.9)0 (0.0)
Salmonella22 (6.3)0 (0.0)
No growth149 (42.9)4 (57.1)
Symptoms
Abdominal pain310 (89.3)6 (85.7)0.552
Duration (day)a3.16 ± 3.493.29 ± 2.220.892
Diarrhea328 (94.5)7 (100.0)> 0.999
Duration (day)a3.31 ± 3.065.43 ± 4.690.277
Maximum number of times per daya7.58 ± 6.1111.00 ± 10.260.413
Hematochezia38 (11.0)0 (0.0)> 0.999
Weight loss78 (22.5)2 (28.6)0.658
Vomiting93 (26.8)2 (28.6)> 0.999
Fever249 (71.8)6 (85.7)0.678
Duration (day)a1.72 ± 1.552.86 ± 1.770.143
Laboratory findingsa
On admission
Leukocyte count (× 103/mm3)9.51 ± 3.869.21 ± 3.320.823
C-reactive protein (mg/dL)96.56 ± 82.7765.29 ± 52.710.172
Maximum value during hospitalization
Leukocyte count (× 103/mm3)9.98 ± 4.0112.33 ± 6.250.359
C-reactive protein (mg/dL)109.56 ± 82.6268.57 ± 53.130.089
Total hospital stay (day)a4.83 ± 1.724.71 ± 1.600.853
Total treatment period (day)a12.00 ± 3.3111.71 ± 2.140.743
Maximum body temperature during hospitalization (ºC)a37.96 ± 0.9138.00 ± 0.820.899

aContinuous variables are summarized as mean ± SD and analyzed with Student’s t test or the Mann–Whitney U test. All other data are presented as n (%) and analyzed by chi-square test or Fisher’s exact test.

PI-IBS, post-infectious irritable bowel syndrome; Y. enterocolitica, Yersinia enterocolitica; E. coli, Escherichia coli; STEC, Shiga-toxin producing E. coli; EPEC, enteropathogenic E. coli; ETEC, enterotoxigenic E. coli; EAEC, enteroaggregative E. coli; C. perfringens, Clostridium perfringens; C. difficile, Clostridioides difficile.



No significant differences were observed between the 2 groups in terms of CRP levels and leukocyte counts, which were measured on the hospitalization day. There were also no significant differences between the 2 groups in the maximum CRP levels and leukocyte counts measured during hospitalization.

Changes in Gastrointestinal Symptoms During the 1-year Follow-up

The number of patients without abdominal pain was 227 (64.1%), 266 (75.1%), and 306 (86.4%) in the 3, 6, and 12-month surveys, respectively (Table 3). In the 3-month, 6-month, and 12-month surveys, 96 (27.1%), 53 (15.0%), and 29 patients (8.2%) had abdominal pain more than once a month, and 11 (3.1%), 8 (2.3%), and 2 patients (0.6%) had abdominal pain more than once a week. The number of patients with diarrhea (Bristol type 6 or 7, > 25% of all bowel movements) was 114 (32.2%), 82 (23.2%), and 43 (12.1%) in the 3, 6, and 12-month surveys, respectively.

Table 3 . Changes in Gastrointestinal Symptoms During the 1-year Follow-up Period After Acute Gastroenteritis

Gastrointestinal symptomsTotal (N = 354)
3-mo surveyNo abdominal pain227 (64.1)
Abdominal pain (more than once a month)96 (27.1)
Abdominal pain (more than once a week)11 (3.1)
Diarrhea (Bristol type 6 or 7, > 25% of all bowel movements)114 (32.2)
PI-IBS (fulfill the criteria)7 (2.0)
6-mo surveyNo abdominal pain266 (75.1)
Abdominal pain (more than once a month)53 (15.0)
Abdominal pain (more than once a week)8 (2.3)
Diarrhea (Bristol type 6 or 7, > 25% of all bowel movements)82 (23.2)
PI-IBS (fulfill the criteria)5 (1.4)
12-mo surveyNo abdominal pain306 (86.4)
Abdominal pain (more than once a month)29 (8.2)
Abdominal pain (more than once a week)2 (0.6)
Diarrhea (Bristol type 6 or 7, > 25% of all bowel movements)43 (12.1)
PI-IBS (fulfill the criteria)1 (0.3)

PI-IBS, post-infectious irritable bowel syndrome.

Data are presented as n (%).



Of the total of 7 PI-IBS patients identified in the 3-month survey, 5 were also met PI-IBS criteria in the 6-month survey and 1 in the 12-month survey (Supplementary Table). Of the PI-IBS patients, pathogenic organisms were identified in 3 cases, all of which were Campylobacter. None of the patients without PI-IBS at 3 months were diagnosed with PI-IBS at 6 or 12 months. All PI-IBS patients expressed IBS-D type.

Risk Factors for Persistent Diarrhea for More Than 3 Months

Patients with diarrhea in more than 25% of all bowel movements in the 3-month survey were more female than those who did not (P = 0.006), were more likely to be infected with enteropathogenic Escherichia coli (EPEC) (P = 0.039), and had a longer total treatment period (P = 0.022) (Table 4). A multivariate analysis revealed that female sex (OR, 2.040 [95% CI, 1.269-3.280]; P = 0.003), EPEC infection (OR, 9.889 [95% CI, 1.069-91.496]; P = 0.044), and longer total treatment period (OR, 1.087 [95% CI, 1.014-1.165]; P = 0.018) were independent risk factors for persistent diarrhea lasting ≥ 3 months after acute infectious enteritis (Table 5).

Table 4 . Comparison of Patients With Diarrhea in More Than 25% of All Bowel Movements in the 3-Month Survey and Other Patients

VariablesPatients with diarrhea (> 25% of all bowel movements in the 3-mo survey, n = 114)Other patients (n = 240)P-value
Age (yr)a41.55 ± 16.4540.76 ± 15.880.668
Female sex76 (66.7)122 (50.8)0.006
Location of enteritis on CT scan0.503
Pancolitis62 (54.4)134 (55.8)
Right colitis29 (25.4)73 (30.4)
Left colitis8 (7.0)15 (6.3)
Inflammation confined to the small bowel5 (4.4)4 (1.7)
No apparent inflammation on CT8 (7.0)11 (4.6)
CT scan not performed2 (1.8)3 (1.3)
Causative organism
Aeromonas1 (0.9)1 (0.4)0.541
Y. enterocolitica0 (0.0)1 (0.4)> 0.999
Vibrio0 (0.0)1 (0.4)> 0.999
Shigella2 (1.8)1 (0.4)0.244
E. coil O157:H74 (3.5)7 (2.9)0.751
STEC1 (0.9)0 (0.0)0.322
EPEC4 (3.5)1 (0.4)0.039
ETEC0 (0.0)1 (0.4)> 0.999
EAEC1 (0.9)1 (0.4)0.541
Enteric adenovirus0 (0.0)1 (0.4)> 0.999
Astrovirus2 (1.8)1 (0.4)0.244
Norovirus GI2 (1.8)7 (2.9)0.724
Norovirus G23 (2.6)1 (0.4)0.100
Campylobacter53 (46.5)90 (37.5)0.132
C. perfringens2 (1.8)8 (3.3)0.511
C. difficile1 (0.9)9 (3.8)0.177
Salmonella7 (6.1)15 (6.3)> 0.999
Symptoms
Abdominal pain100 (87.7)216 (90.0)0.517
Duration (day)a3.36 ± 4.413.08 ± 2.910.531
Diarrhea106 (93.0)229 (95.4)0.347
Duration (day)a3.56 ± 3.803.25 ± 2.720.427
Maximum number of times per daya7.82 ± 5.957.57 ± 6.350.710
Hematochezia9 (7.9)29 (12.1)0.274
Weight loss25 (21.9)55 (22.9)0.892
Vomiting33 (28.9)62 (25.8)0.608
Fever85 (74.6)170 (70.8)0.527
Duration (day)a1.89 ± 1.721.68 ± 1.480.271
Laboratory findingsa
On admission
Leukocyte count (×103/mm3)a9.44 ± 3.959.53 ± 3.800.831
C-reactive protein (mg/L)a87.42 ± 74.5099.99 ± 85.680.159
Maximum value during hospitalization
Leukocyte count (×103/mm3)a10.26 ± 4.559.92 ± 3.820.498
C-reactive protein (mg/L)a98.06 ± 72.27113.83 ± 86.320.073
Total hospital stay (day)a4.93 ± 1.314.78 ± 1.880.396
Total treatment period (day)a12.59 ± 3.4211.71 ± 3.200.022
Maximum body temperature during hospitalization (ºC)a37.99 ± 0.9037.94 ± 0.910.651

aContinuous variables are summarized as mean ± SD and analyzed with Student’s t test or the Mann–Whitney U test. All other data are presented as n(%) and analyzed by chi-square test or Fisher’s exact test.

Y. enterocolitica, Yersinia enterocolitica; E. coli, Escherichia coli; STEC, Shiga-toxin producing E. coli; EPEC, enteropathogenic E. coli; ETEC, enterotoxigenic E. coli; EAEC, enteroaggregative E. coli; C. perfringens, Clostridium perfringens; C. difficile, Clostridioides difficile.



Table 5 . The Predictors for Patients With Diarrhea Lasting More Than 3 Months After Acute Gastroenteritis

VariablesUnivariate analysisMultivariate analysis
OR (95% CI)P-valueAdjusted OR (95% CI)P-value
Female sex1.934 (1.216-3.078)0.0052.040 (1.269-3.280)0.003
EPEC8.691 (0.960-78.664)0.0549.889 (1.069-91.496)0.044
Total treatment period1.084 (1.013-1.161)0.0201.087 (1.014-1.165)0.018

EPEC, enteropathogenic Escherichia coli.

Univariate and multivariate logistic regression analyses were performed.


Discussion

This multi-center study with a long follow-up period allowed us to determine the incidence and clinical course of PI-IBS in East Asia, a relatively understudied region. According to the definition of PI-IBS that symptoms developed after infectious diarrhea, in our study, only 2% of patients were diagnosed with PI-IBS at 1 year of follow-up after enteritis. Therefore, compared to what is known, the incidence of PI-IBS in Korea is estimated to be lower than in other countries. However, many patients had diarrhea for a long time after enteritis, even if they did not meet the diagnostic criteria for IBS. Diarrhea persisted for 3 months after enteritis in 32% of all enteritis patients and for 1 year in 12%. Therefore, patients with severe infectious enteritis may continue to have symptoms for a considerable period after recovery. However, it seems rare that symptoms are severe and long-lasting enough to warrant a diagnosis of IBS.

In our study, all subtypes of PI-IBS were identified as IBS-D. In previous studies, IBS that occurred after infection was mostly IBS-D.7-9,11,12 Also, of the 7 patients who developed PI-IBS, only 1 patient had symptoms that lasted up to 1 year. Therefore, the natural course of Pi-IBS is relatively not bad, and in many cases, it is thought to improve slowly. The causative agent was confirmed to be Campylobacter in 3 out of 7 cases, but no significant correlation was observed.

Previous studies investigated risk factors for the occurrence of PI-IBS, such as young age, female sex, the duration of diarrhea, and severe enteritis.3,4,10,12 Several studies have also reported differences according to infection strains. However, according to a recent meta-analysis, there was no significant difference in incidence according to strain.9 No significant risk factors were associated with the development of PI-IBS in our study. Previously identified factors of age, female sex, diarrhea period, severe enteritis symptoms, and causative strain were not significantly associated, nor were underlying disease, enteritis location, or blood test findings. The lack of significant associations between these known risk factors and PI-IBS in our analysis may be due to the lack of statistical power associated with the low prevalence of PI-IBS in the study population. In contrast, regarding persistent diarrhea lasting more than 3 months, female sex, the total duration of treatment, and EPEC infection were identified as independent risk factors, consistent with the known risk factors for PI-IBS. These findings suggest that female sex and patients with severe enteric infections may be at an increased risk for subsequent chronic gastrointestinal symptoms, including persistent diarrhea and abdominal pain, even if the symptoms do not meet the diagnostic criteria for PI-IBS.

EPEC, a major cause of infantile diarrhea in developing countries, is the second most common pathogen identified in diarrheal stool samples from symptomatic adults in developed countries.14,15 To date, no study has shown that EPEC infections cause PI-IBS. However, EPEC infection is characterized by the formation of attaching and effacing lesions in the small intestine, therefore these bacterial properties may be the cause of persistent diarrhea after infection.14,16

Although several studies have been conducted on PI-IBS, this study is significant in that East Asian studies are lacking, and few PI-IBS studies have been based on the Rome IV criteria.3 However, this study had some limitations. First, the subject's underlying gastrointestinal symptoms before the onset of enteritis could not be accurately investigated. Whether the patients participating in the study originally had IBS was confirmed by doctors questions on an outpatient basis after discharge. Since patients answered by recalling their usual symptoms from 6 months earlier, the accuracy of their answers may be not so high. In addition, some of the patients with persistent diarrhea after enteritis may have been people who often have diarrhea. More accurate results could have been obtained if the patients included in the study were asked to record their usual bowel habits from the beginning. Second, the treatment period can be both a cause and a consequence of PI-IBS. In our study, the total duration of treatment correlated with the occurrence of persistent diarrhea. However, the long treatment period in PI-IBS patients may have caused the disease to develop, or it could also have been the result of persistent symptoms. Therefore, the results should be cautiously interpreted. Third, the prevalence of PI-IBS in our study was rather low at 2%, which warrants discussion. IBS is known to affect 5-10% of the general population.1,17 However, a previous study reported that the prevalence of IBS based on Rome IV criteria was 4.7% in Korea and 2.2% in Japan.18 Therefore, the prevalence of IBS in East Asia is not as high as in other parts of the world, which may explain our findings of a low prevalence of PI-IBS. Furthermore, we excluded patients who had already been diagnosed with IBS before acute enteritis. In other words, only patients who developed new IBS symptoms after enteritis were defined as PI-IBS in this study. Therefore, the prevalence of PI-IBS in our study may differ from the prevalence of IBS in the general population. In addition, the diagnosis of PI-IBS was made based on telephone survey, not in-person interview, which may have reduced diagnostic accuracy. The fourth limitation is that the study population was a tertiary care center-based cohort, which makes it difficult to generalize the results, and our results may have underestimated the true prevalence of PI-IBS in general population. Lastly, we did not check how well patients took their discharge medications. Therefore, the total treatment period for some patients may have been overestimated.

In conclusion, the incidence of PI-IBS in Korea was relatively low at 2%, and the symptoms mostly improved over time. No risk factors associated with the development of PI-IBS were found in this study. However, female sex, EPEC infection, and severe or long-lasting enteritis were associated with persistent diarrhea lasting more than 3 months after acute infectious enteritis. Therefore, it is necessary to make patients with these risk factors aware and reassure them that the sequelae of diarrhea after enteritis may persist. IBS symptoms may persist after severe enteritis, but it seems rare for symptoms to be severe and long-lasting enough to be diagnosed as PI-IBS in Korea.

Financial support

None.

Conflicts of interest

None.

Author contributions

Sang Pyo Lee: study concept, design, analysis and interpretation of data, and drafting of the manuscript; Jae Gon Lee: study concept, interpretation of data, and critical revision of the manuscript; and Hyun Joo Jang, Sea Hyub Kae, Woon Geon Shin, Seung In Seo, Hyun Lim, Ho Suk Kang, Jae Seung Soh, Chang Seok Bang, Young Joo Yang, Gwang Ho Baik, Jin Bae Kim, Yu Jin Kim, and Chang Kyo Oh: acquisition of the data.

Supplementary Material

Note: To access the supplementary table mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm24018.

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