Predictors for the Development of Post-infection Irritable Bowel Syndrome after Acute Gastroenteritis: A Prospective Study

Abstract

Background

Post-infection irritable bowel syndrome (PI-IBS) is seen following an episode of acute gastroenteritis (AGE). Long-term studies have suggested that the risk of developing PI-IBS increases up to sixfold after gastrointestinal infection. This study aims to evaluate the incidence of PI-IBS and identify its risk factors.

Methods

This prospective study was performed over a period of 1 year on AGE patients admitted to a tertiary care hospital in South India. Clinical and demographic characteristics were noted, and risk factors were evaluated. An IBS questionnaire ruled out ongoing or pre-existing IBS. The patients were followed up after 6 months to look for the development of IBS (Rome IV criteria).

Results

Out of 100 hospitalized AGE patients, one-fourth developed PI-IBS after 6 months. Out of them, 18 patients had the diarrhea-predominant (IBS-D) type, and the remaining 7 had the constipation-predominant (IBS-C) type. The factors that were significantly associated with PI-IBS were younger age, longer duration of AGE, depression, and abdominal cramps. On multivariate logistic regression analysis, longer duration of AGE (>7 days; p-value = 0.0040) and presence of abdominal cramps (p-value = 0.0130) were found to significantly influence the development of PI-IBS at 6 months.

Conclusion

One-fourth of the patients in our study developed PI-IBS. Younger age, depression, longer duration of diarrhea, and abdominal cramps were statistically significant risk factors for the development of PI-IBS. Physicians should keep a high suspicion for PI-IBS in patients with such predisposing risk factors.

Keywords

bowel - Bristol - constipation - depression - diarrhea - gastroenteritis - infection - PI-IBS - Rome - stool

Introduction

Irritable bowel syndrome (IBS) is a common condition diagnosed in the daily outpatient department. It is characterized by abdominal pain and altered bowel habits, with no detectable structural abnormalities and normal routine diagnostic tests.[1] IBS is a form of gut–brain interaction disorder as most intestinal functions are found to be regulated by the brain. It affects approximately 8 to 9% of the world population.[2]

Post-infection IBS (PI-IBS) is development of de novo IBS symptoms (by Rome criteria) in an individual after he or she experiences an episode of acute gastroenteritis (AGE), which includes two or more of the following: fever, vomiting, diarrhea, or a positive stool culture.[3] [4] This includes persistent abdominal discomfort, diarrhea, and bloating despite clearance of the inciting pathogen. Since the first description of PI-IBS by Chaudhary and Truelove in 1962, numerous studies have demonstrated relationship between AGE and development of subsequent IBS.[5] Long-term studies have suggested that the risk for development of PI-IBS increases up to sixfold after gastrointestinal infection.[6]

India has a high incidence of AGE, hence a lot of people are at risk of developing PI-IBS. There is a lack of prospective studies showing incidence of PI-IBS as per Rome IV criteria in India. Identification of risk factors leading to PI-IBS would give us early interventional opportunities to ameliorate symptom development and to educate the patients with AGE about the possibility of development of IBS in future. Hence, this study has been performed to study the incidence of PI-IBS and to identify the risk factors associated with the development of PI-IBS.

Methods

This study included patients aged 18 years or older who were diagnosed with AGE admitted in the medical ward of Dr. Prabhakar Kore Hospital and Medical Research Center, Belagavi. It was performed over a period of 1 year. AGE was defined as per the Rome Foundation Working Team report on PI-IBS (2019), i.e., presence of a positive stool culture in a symptomatic individual or presence of two or more of: fever, vomiting, and diarrhea for a duration of less than 2 weeks.[7] The patients who did not give consent to be a part of the study or those with a history of chronic diarrhea or diagnosed cases of disorders that may cause chronic diarrhea such as inflammatory bowel disease, tuberculosis, prior abdominal surgery, radiation enterocolitis, hereditary polyposis, etc., were excluded from the study. A written informed consent was obtained from all patients included in the study.

All included AGE patients were subjected to an IBS questionnaire (based on Rome IV) that elaborately evaluated patient's symptoms along a timeline, along with questions to exclude other functional gastrointestinal disorders (FGIDs) like functional dyspepsia at the time of AGE episode and after 6 months. Those found to be having IBS already were excluded from the study. Those not having IBS at the time of AGE episode were assessed for various risk factors associated with the development of PI-IBS in a face-to-face interview. These included age, gender, duration of episode, peak stool frequency per day, abdominal cramping, bloody stools, fever, use of antibiotics, anemia, direct contact with livestock, and psychological factors (anxiety and depression). The Hospital Anxiety and Depression Scale (HADS) questionnaire was used to ascertain psychological status. Stool samples were collected for microscopic study and culture. Follow-up survey was done after 6 months of AGE episode either as a face-to-face interview or telephonically to diagnose post-infection IBS.

The Rome IV criteria for IBS is as follows:

Recurrent abdominal pain, on an average, at least 1 day per week in the last 3 months, with symptom onset at least 6 months before diagnosis, associated with ≥2 of the following:

• Defecation.

• A change in frequency of stool.

• A change in form (appearance) of stool.

Every patient was asked to identify the type of stool they were passing usually as per the Bristol stool chart. The risk factors were compared in the groups that developed PI-IBS and that did not. This study was approved by Institutional Ethics Committee on Human Subjects Research of Jawaharlal Nehru Medical College, Belagavi (approval MDC/DOME/38) on November 24, 2018 and was performed according to the ethical guidelines of the 1975 Declaration of Helsinki and its amendments.

Statistical Analysis

All the data were analyzed using the Statistical Package for Social Sciences (SPSS) software (SPSS for Windows, version 20, SPSS Inc., Chicago, United States). The categorical data were expressed in terms of rates, ratio, and percentage and the continuous data were expressed in terms of mean ± standard deviation. The association between risk factors and development of PI-IBS was tested using the Chi-square test. Odds ratio was calculated for each risk factor. Multiple logistic regression analysis was used to study the risk factors together and individually. Probability (p) value of ≤0.05 was considered statistically significant.

Results

A total of 100 patients with AGE who met the inclusion criteria were enrolled in the present study. They were followed up after 6 months of the AGE episode and PI-IBS was diagnosed based on Rome IV criteria. Twenty-five patients, i.e., one-fourth of the total patients, developed PI-IBS in our study after 6 months of AGE ([Fig. 1]). Eighteen out of these 25 patients (72%) had diarrhea-predominant IBS (IBS-D) and the remaining 7 (28%) had constipation-predominant IBS (IBS-C), as represented in [Fig. 2]. Out of the 25 patients who developed PI-IBS, 28% patients were passing Bristol type II stool, whereas 72% were passing Bristol type VI stool. Our study sample had 50% males and 50% females; however, 22% males and 28% females developed PI-IBS at 6 months. Sex was not statistically significant as a risk factor in our study (p-value: 0.4880). People of younger age developed PI-IBS more than those over 60 years of age (30.56% of the patients with age ≤60 years vs. 10.71% of those >60 years; p-value = 0.040). Fever, vomiting, number of stools per day, use of antibiotics, and contact with livestock were not significantly associated with development of PI-IBS. However, 90.91% of patients with longer duration of AGE (>7 days) developed PI-IBS as compared with only 16.85% in those with duration of AGE ≤7 days (p-value = 0.0001). Presence of abdominal cramps was also significantly associated with development of PI-IBS (p-value = 0.0001). In our study, stool cultures of all patients were negative for enteropathogens; however, significant pus cells were present in all stool samples. Psychological factors did play some role in the development of PI-IBS. In total, 40.91% of those with depression during the episode of AGE developed PI-IBS as compared with only 20.51% of those without depression (p-value = 0.050). Anxiety was not a significant risk factor. Presence of occult blood in stool and anemia were not found to be significant risk factors in this study. [Table 1] summarizes the various risk factors at the time of AGE episode among patients who did and who did not develop PI-IBS and their individual significance (p-value). On multiple logistic regression analysis ([Table 2]), duration of AGE (>7 days) (adjusted OR [AOR]: 71.55; 95% confidence interval [CI]: 3.83–1,337.58; p-value = 0.0040) and presence of abdominal cramps (AOR: 5.07; 95% CI: 1.42–18.18; p-value = 0.0130) were found to significantly influence the development of PI-IBS at 6 months, when compared with the other risk factors.

Fig. 1 Study flowchart. AGE, acute gastroenteritis; IBS, irritable bowel syndrome; PI-IBS, post-infection irritable bowel syndrome.

Fig. 2 Incidence of PI-IBS and subtypes. IBS-C, irritable bowel syndrome-constipation predominant; IBS-D, irritable bowel syndrome-diarrhea predominant; IBS-M, irritable bowel syndrome-mixed type.

Table 1 Comparison of risk factors at the time of AGE between patients who did and did not develop PI-IBS

Risk factor	Patients who developed PI-IBS, n = 25 (%)	Patients who did not develop PI-IBS, n = 75, (%)	p-Value
Fever	23 (92)	56 (74.66)	0.0650
Vomiting	24 (96)	66 (88)	0.2480
Stool occult blood	1 (4)	10 (13.33)	0.1960
Direct contact with livestock	2 (8)	8 (10.66)	0.7000
Antibiotics use	24 (96)	61 (81.33)	0.0750
Anxiety	9 (36)	14 (18.66)	0.0750
Depression	9 (36)	13 (17.33)	0.0500[a]
Duration of AGE >7 days	10 (40)	1 (1.33)	0.0001[a]
Abdominal cramps	20 (80)	23 (30.66)	0.0001[a]

Abbreviations: AGE, acute gastroenteritis; PI-IBS, post-infection irritable bowel syndrome.

^a p < 0.05.

Table 2 Multiple logistic regression analysis for incidence of PI-IBS

Independent factors	Unadjusted OR	95% CI for OR		p-Value	AOR	95% CI for OR		p-Value
		Lower	Upper			Lower	Upper
Age groups (≤60 vs. >60 y)	0.12	0.04	0.40	0.0010[a]	0.33	0.07	1.57	0.1630
Sex (male vs. female)	0.39	0.21	0.72	0.0030[a]	1.11	0.32	3.91	0.8710
Fever (no vs. yes)	0.41	0.25	0.67	0.0001[a]	0.62	0.16	2.47	0.5010
Vomiting (no vs. yes)	0.36	0.23	0.58	0.0001[a]	0.28	0.06	1.32	0.1080
No. of stools per day (≤6 vs. >6)	0.37	0.22	0.63	0.0001[a]	0.45	0.12	1.74	0.2500
Antibiotics (not use vs. use)	0.39	0.25	0.63	0.0001[a]	0.89	0.14	5.72	0.9010
Duration of AGE (≤7 vs. >7))	10.00	1.28	78.12	0.0280[a]	71.55	3.83	1,337.58	0.0040[a]
Abdominal cramps (no vs. yes)	0.87	0.48	1.58	0.6480	5.07	1.42	18.18	0.0130[a]
Anxiety (no vs. yes)	0.64	0.28	1.49	0.3010	2.19	0.53	9.13	0.2820
Depression (no vs. yes)	0.69	0.30	1.62	0.3960	2.68	0.65	11.08	0.1730
Contact with livestock (no vs. yes)	0.25	0.05	1.18	0.0800	0.69	0.07	6.91	0.7520
Stool occult blood (no vs. yes)	0.10	0.01	0.78	0.0280[a]	0.17	0.02	1.88	0.1480

Abbreviations: AGE, acute gastroenteritis; AOP, adjusted odds ratio; CI, confidence interval; OR, odds ratio; PI-IBS, post-infection irritable bowel syndrome.

^a p < 0.05.

Discussion

As IBS is a common diagnosis in the outpatient department, a prospective study helps us better in establishing AGE as an etiology for developing IBS, minimizing recall bias and enhancing the quality of follow-ups and hence the data regarding risk factors obtained. Although AGE is very common in tropical countries with poor hygiene, information on PI-IBS is very scarce from these countries. Gwee et al, in 1996, had studied a group of 75 patients with AGE, 20 of which had PI-IBS at 6 months (26.6%).[8] We found the incidence of PI-IBS to be 25% by Rome IV criteria in our study. The Walkerton Health Study had also reported approximately 30% incidence of PI-IBS in subjects with AGE.[4] Recently, in a study with 136 patients of AGE in Orissa, the incidence of PI-IBS was reported to be 25.7% at 6 months by Rome III criteria.[9] However, in a study in 2006, only 3.7% incidence of PI-IBS in community subjects was noted.[10] This was diagnosed by Manning and Rome I criteria, which currently are obsolete.

In the present study, females developed PI-IBS more than males (14 vs. 11); however, it was not statistically significant. Klem et al, in a systematic review and meta-analysis in 2017, had reported that females are 2.2 times more likely to develop PI-IBS.[11] Ruigómez et al and Wensaas et al have also reported PI-IBS to be more prevalent in females but, it may not be statistically significant.[12] [13] McKendrick and Read found in their study that women were almost five times more as compared with men among those who had persistent symptoms after AGE.[14] Age less than or equal to 60 years was found to be statistically significant in our study for the development of PI-IBS. This is comparable to majority of the studies conducted to study risk factors associated with the development of PI-IBS.[4] [6] [9] Ji et al, on the contrary, did not find any significant difference in ages between patients who did and did not develop PI-IBS.[15]

In our study, duration of AGE of more than 7 days and presence of abdominal cramps were two independently significant risk factors (p = 0.0001) associated with the development of PI-IBS. Singh et al, in an Indian study, have validated the same with duration of AGE and abdominal cramps getting more points in a PI-IBS risk score.[16] A study by Kowalcyk et al also described these two factors as statistically significant for development of PI-IBS.[17] Paula et al had studied the relationship between antibiotic use and FGID.[18] We found that though a higher number of patients with history of antibiotic consumption developed PI-IBS, it was not statistically significant. More elaborate studies with details of antibiotics might be needed to study their role in the development of PI-IBS. Psychological disorders like depression and anxiety have been long associated with FGIDs. In our study, patients with depression, according to HADS questionnaire, were found to have statistically significant risk of developing PI-IBS (p = 0.050). Anxiety, however, was not statistically significant. Wouters et al had observed that both anxiety and depression led to increased risk of developing PI-IBS.[19] The HADS questionnaire has been validated for clinical use in the general population and has been found to perform well in diagnosing anxiety and depression.[20] Sykes et al also found that anxiety predisposed to development of IBS.[21] In a review of clinical and epidemiological perspectives of IBS in India, Rahman et al observed that majority of patients could not be classified as IBS-C or IBS-D and were put into a mixed category (IBS-M) as most of them could not define their symptoms in accordance with frequency of stool criteria for constipation or diarrhea.[22] However, the patients in our study who developed PI-IBS could be subtyped with 72% patients falling under the IBS-D category.

Our study did not show any stool cultures with growth of enteropathogens, hence we could not relate the type of organism causing AGE as a risk factor for the development of PI-IBS. As most of our patients had consumed antibiotics prior to hospital admission, it may have influenced the result of stool cultures. Salmonella and Campylobacter causing AGE have been found to commonly predispose to PI-IBS.[23] Genetic testing also plays a significant role in determining genetic risk factors that predispose an individual to PI-IBS, like mutations in toll-like receptors, interleukin-6, and cadherin-1.[24] This could yield more informative results in future prospective studies.

The patients in our study were not evaluated for conditions like tropical sprue and small intestinal bacterial overgrowth (SIBO) that have been reported in recent studies in the Indian subcontinent.[25] The frequency of SIBO has been reported to vary from 4 to 78% in patients with IBS, especially diarrhea-predominant.[26] The frequency of tropical sprue has not been determined in association with PI-IBS due to lack of studies in this area. In one study from Bangladesh, 9% of the patients with PI-IBS according to Rome III criteria had at least two abnormal mucosal absorption tests indicating tropical sprue or post-infection malabsorption syndrome (PI-MAS).[27] Ghoshal and Rahman, in a recent publication, have also suggested the need of larger studies with mucosal absorption tests to estimate the incidence of tropical sprue and PI-MAS, which in the absence of overt malnutrition can mimic PI-IBS.[28] Invasive and expensive investigations like small intestinal biopsies and jejunal aspirates needed to rule out these co-existing conditions were a limitation to our study.

The symptoms of PI-IBS are often treated as new episodes of subsequent AGE, sometimes due to the patients visiting multiple physicians with the same problems. Physicians should keep a high suspicion for PI-IBS, in patients with predisposing risk factors. It is suggested to study a larger cohort, with inclusion of genetic risk factors to extrapolate the statistics to the general population. The molecular mechanisms possibly involved in the pathogenesis of PI-IBS should be investigated for better understanding of the disease, and to plan and strategize therapeutic options. Targeting the gut microbiota and its alteration is currently a topic of focus, and is proving to be promising in the management of PI-IBS.

Conflict of Interest

None declared.

Acknowledgments

None.

Ethical Clearance

The study was approved by the Institutional Ethics Committee of JNMC (KAHER).

Author Contributions

R.A. was responsible for data collection, analysis, manuscript writing, and the formulation of the study protocol. M.P. contributed by assisting with data collection, supervising data interpretation, and supporting the writing process. P.M. participated in data collection, while D.M. was involved in the scientific writing. R.S.P. played a key role in developing the study protocol, overseeing the study, contributing to manuscript writing, and revising the final draft.

Data Availability Statement

There is no data associated with this work.

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Publication History

Received: 26 May 2025

Accepted: 28 July 2025

Article published online:
06 October 2025