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. 2025 Jan 6;37(1):e24209. doi: 10.1002/ajhb.24209

The Developmental Origins of Irritable Bowel Syndrome: A Systematic Review and Meta‐Analysis

Makenna B Lenover Moyer 1,✉, Krishangi Jasani 1, Alexandra B Waldman 2, Vernon M Chinchilli 3, Mary K Shenk 1
PMCID: PMC11701970  PMID: 39760236

ABSTRACT

Objectives

The Developmental Origins of Health and Disease (DOHaD) framework contends that chronic diseases are attributable to behavioral and environmental risks encountered during vital periods of fetal and childhood development. Clinical research investigating irritable bowel syndrome (IBS) largely focuses on adult risk factors, with emerging evidence of epigenetic contributions. Limited work considers potential childhood exposures. This paper applies a life course approach to the study of IBS, exploring the available evidence to ascertain the potential developmental origins of IBS.

Methods

A systematic literature review was conducted adhering to MOOSE and PRISMA protocols, identifying papers from 1970 through April 2024 examining all IBS risk factors during the prenatal, postnatal, childhood, and adolescent periods. Data were extracted from screened papers and analyzed via meta‐analysis using a random effects model.

Results

A total of 27 case–control, cohort, and cross‐sectional studies were identified for analysis. The meta‐analysis revealed significant childhood risk factors for adult IBS, including family history (pooled OR 2.17, 95% CI 1.89–2.49, p < 0.0001, n = 11) and the occurrence of any childhood trauma event (pooled OR 1.61, 95% CI 1.29–2.01, p < 0.0001, n = 6). Physical and sexual trauma were the strongest trauma predictors. Factors including breastfeeding and Cesarean section were not significant.

Conclusions

This study found IBS is strongly predicted by traumatic childhood experiences, as well as having an immediate family member with IBS. These demonstrated environmental and genetic components indicate a potential gene–environment interaction during childhood, suggesting a need for primary research to better understand the developmental origins of IBS.

Keywords: childhood, DOHaD, irritable bowel syndrome, meta‐analysis, risk factor

1. Introduction

Behavioral and environmental experiences during childhood may contribute to adult chronic disease health status, including for cardiovascular disease, type 2 diabetes, and obesity (Inadera 2013). The Developmental Origins of Health and Disease (DOHaD) framework helps to explain how the rise of chronic diseases are not only attributable to adult behavioral–environmental risk factors, but also to behavioral and environmental risks encountered during vital periods of childhood growth and development, including prenatal, perinatal, and early childhood (Gluckman, Buklijas, and Hanson 2016). Maternal health indicators, including nutrition, smoking, and stress, as well as childhood exposures to pollution, stress, and malnutrition, have been demonstrated to disturb social, cognitive, and physical development, including both vital organ systems and the microbiome (Malan‐Muller et al. 2022; Marie‐Mitchell and O'Connor 2013).

Recent developments within the DOHaD space suggest that much of this phenomenon is due to epigenetic changes, or modifications of gene function by environment or behavior, made possible by mechanisms such as DNA methylation and histone mediation (Gluckman, Hanson, and Buklijas 2010; Stilling, Dinan, and Cryan 2014). Individually, characterizing the role of both genetic susceptibility and environmental exposures in disease causality allows us to better ascertain disease risk, but also identify prevention and treatment strategies. For example, one twin study found that environmental factors explained 48%–77% of prostate, colon, or breast cancers (Lichtenstein et al. 2000). Identifying the interaction between genes and environment is critical, as it helps to explain both how early life exposures may lead to later adult illness manifestations, as well as how maternal exposures (either prepregnancy or during the prenatal period) may be passed on intergenerationally to children, increasing disease risk.

This framework has been informative in understanding rising rates of chronic illness, including diabetes and cardiovascular disease, though one such illness which requires further investigation from this lens is irritable bowel syndrome (IBS). IBS is a functional, chronic gastrointestinal disease that affects an upwards of 15% of the United States population and includes symptoms including abdominal pain and changes in bowel patterns, including stool frequency and form (Oka et al. 2020). The illness often carries major emotional and financial burdens for patients, resulting in frequent trips to medical providers, high bills, and time off for the debilitating nature of flare‐ups (Norlin et al. 2019). IBS is diagnosed via symptomatic criteria, the Rome IV criteria, which account for the frequency and duration of abdominal pain alongside disturbed bowel habits (Drossman and Hasler 2016).

While adult behavior and environment, including stress and illness, are clearly demonstrated to contribute to adult IBS status, a smaller body of previous research indicates childhood is an additionally worthwhile avenue of investigation. Childhood trauma is a demonstrated risk factor for adult IBS, as it may disrupt the gut microbiome and brain–gut axis (Berens et al. 2020; Halland et al. 2014; Malan‐Muller et al. 2022; Marie‐Mitchell and O'Connor 2013; Videlock et al. 2009). This association was reaffirmed via a previous meta‐analysis (Joshee et al. 2022), though not connected to a DOHaD framework. The brain–gut axis is the connection between the enteric nervous system (or nerves that line the digestive tract) and central nervous system (Drossman and Hasler 2016). Disruption of either nervous system impacts the other in adult IBS patients (Alsubaie et al. 2022; Beesley, Rhodes, and Salmon 2010; Foster, Rinaman, and Cryan 2017; O'Mahony et al. 2017; Stilling, Dinan, and Cryan 2014). It is not yet demonstrated if this dysregulation begins during childhood and perpetuates into adulthood or is adult‐onset.

Despite this evidence demonstrating IBS has roots in critical childhood periods, the current literature largely focuses on adult risk factors, suggesting it may benefit from a DOHaD approach dissecting the role of early life. Existing genetic research indicates that IBS is largely an illness that has its origins in behavior and environment, as few candidate genes have been identified (Stilling, Dinan, and Cryan 2014). That being said, work has been done looking at the role of family history in IBS, and evidence does suggest the disease is often present in shared living groups (Saito et al. 2010; Waehrens et al. 2018). In a twin study, monozygotic twins had a higher risk of IBS than dizygotic twins, demonstrating a potential genetic component (Bengtson et al. 2006). These contradictory findings signal a potential gene‐by‐environment interaction contributing to IBS risk. This is further reinforced by evidence of epigenetic changes in animal models studies investigating the interaction of stress, DNA methylation, and IBS (Mahurkar‐Joshi and Chang 2020).

It is clear that IBS is an illness with complex etiology, with a potential foundation for the illness laid during critical developmental periods. This may be due strictly to childhood environmental exposures, or epigenetic modifications that either occur during childhood or intergenerationally via the mother. Since a thorough life course approach has not yet been employed to study the IBS disease trajectory, we hypothesize IBS is an illness with developmental origins driven by early life exposures. To begin testing this hypothesis, we conduct a systematic review and meta‐analysis assessing the associations between prenatal, perinatal, and childhood environmental exposures and adult IBS outcomes. We aim to ascertain if there is significant existing evidence of the developmental origins of IBS by examining the effects of preadulthood genetic and environmental exposures on adult populations both with and without IBS, with the goal of motivating and directing further primary research.

2. Materials and Methods

A systematic literature review was conducted with the assistance of an information specialist, adhering to the Meta‐Analyses and Systematic Reviews of Observational Studies (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines (Brooke, Schwartz, and Pawlik 2021; Page et al. 2021).

2.1. Literature Search Strategy

Electronic searches were executed on PubMed, Web of Science, and CAB Abstracts with search dates from 1970 through April 2024. Relevant keywords for childhood risk factors were identified via a previous scoping review (Lenover and Shenk 2023), including “irritable bowel syndrome,” “risk factor,” “behavior,” “health correlate,” “etiology,” “environment,” “exposure,” “adult,” “child,” “infant,” “infancy,” “adolescent,” “teen,” “youth,” “maternal,” “mother,” “prenatal,” “antenatal,” “postnatal,” and “perinatal.” Full search inputs and metadata are available in Appendix S1. Additionally, the reference list as well as the citing literature of each included article were reviewed and considered for inclusion. Sources were de‐duplicated, then imported into Rayyan for management and screening (Ouzzani et al. 2016).

2.2. Screening

First, title and abstract screenings were conducted by two researchers (MBL & ABW) to identify potential articles using the following criteria: (1) study population was adult (ages 18 and over), (2) IBS status was a reported outcome, (3) study included both groups with and without IBS, either via a formal control group or a population sample, (4) study examined prenatal, perinatal, postnatal, or childhood environmental, behavioral, or familial risk factors and exposures, and (5) article reported an original (primary) research study. Family history studies were included as a proxy for genetic risk. The two researchers conducted this search independently based on these criteria, then a third researcher (MKS) adjudicated any disagreements.

Following the title abstract screening, the full text of each included article was then evaluated by three researchers (MBL, ABW, & KJ), using the same criteria as the title and abstract screening in addition to one other: that the study reported risk estimates including the odds ratios (OR) or mean difference (MD) alongside the 95% confidence interval (CI). Any studies that did not meet these criteria, or studies where risk estimates could not be obtained either directly from the paper or after further correspondence with the authors, were excluded.

2.3. Data Extraction and Quality

For all included studies, three researchers (M.B.L.M., A.B.W., and K.J.), independently extracted relevant data (Appendix S2). Any discrepancies between extractions were resolved via discussion between the authors. In addition to the citation, researchers extracted data including country or place of origin, IBS diagnosis method, exposure measurement method, sample size, and the unadjusted odds ratio and 95% confidence interval for each variable of interest. Since this meta‐analysis includes a variety of non‐randomized observational studies, including cross‐sectional and case–control, a quality assessment was conducted (M.B.L.M. and A.B.W.) using JBI's critical appraisal tools and checklists (Moolah et al. 2020).

2.4. Statistical Analysis

Papers were first divided by their risk factor of interest (i.e., family history, birth pathway, breastfeeding). The measures of association (odds ratio, mean difference) and associated 95% confidence intervals were pooled and analyzed using the DerSimonian–Laird random effects method, and heterogeneity was assessed using the I 2 statistic. Sub‐analyses were then conducted by diagnosis method, study country of origin, and study type. To test for publication bias in meta‐analyses with greater than two studies, we investigated asymmetry via Egger's test. p values below 0.05 were considered statistically significant, and all analyses were done in RStudio using the “metafor” package (R Core Team 2024; R Studio Team 2020; Viechtbauer 2010).

3. Results

3.1. Literature Search

Our initial literature search resulted in a total of 851 sources, as well as 13 additional sources through citation chain searching (Figure 1). After duplicates were removed, 728 records remained and were screened for title/abstract criteria resulting in 73 candidates for inclusion in the meta‐analysis. Then the full texts of these 73 articles were assessed, and articles were removed for issues with quality and study design, missing data, or not having the right predictors or outcome variables. After screening was complete, a total of 42 case–control, cohort, and cross‐sectional studies were included in this review, covering a total of 4 838 687 participants. Key characteristics of papers in the sample are included in Table S1. There were 15 case–control studies, 10 cohort studies, and 17 cross‐sectional studies. Publication dates range from 1993 to April 2024, and sample size ranged from n = 103 (Saito 2008) to n = 2 056 430 (Olén et al. 2018). The geographic range of the studies included the United States (18 papers), the United Kingdom (seven papers), Saudi Arabia (three papers), Sweden (three papers), Australia (three papers), Mexico (two papers), Italy (one paper), Spain (one paper), the Netherlands (one paper), Germany (one paper), New Zealand (one paper), and Turkey (one paper). IBS was diagnosed using Rome or Manning criteria in 23 papers and relied on physician diagnosis in 12 papers. Seven papers only used self‐reported IBS status.

FIGURE 1.

FIGURE 1

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Prisma flow chart of search and screening process.

3.2. Meta‐Analysis

Any reported childhood exposure variable with two or more studies was investigated via meta‐analysis, and those with less than two studies were qualitatively described. Analyses exploring environmental and familial childhood exposures related to development are reported below (Table 1), while a qualitative review of additional studies not eligible for meta‐analysis can be found in Appendix S3. Two major significant risk factors were uncovered during this meta‐analysis: childhood trauma and family history. Birth factors, including breastfeeding and birth pathway, were not found to be significant risk factors.

TABLE 1.

Results for the random effects models for the investigated childhood risk factors.

Risk factor # studies Pooled OR 95% CI p
Childhood trauma 6 1.61 1.29–2.01 < 0.0001
Childhood sexual abuse 9 1.57 1.14–2.18 0.0061
Childhood sexual abuse (Rome and Manning diagnosis) 4 1.90 1.35–2.67 0.0002
Childhood physical abuse 9 1.37 1.04–1.82 0.0275
Childhood physical abuse (Rome and Manning diagnosis) 5 1.56 1.04–2.34 0.03
Childhood verbal abuse 2 1.67 0.87–3.23 0.1245
Childhood emotional abuse 4 1.69 0.88–3.25 0.1128
Parental divorce 3 1.08 0.9–1.30 0.4201
Family death 2 1.26 0.87–1.83 0.2169
Family mental illness 4 1.88 1.14–3.10 0.0129
Family history 11 2.17 1.89–2.49 < 0.0001
Family history (United States) 4 2.77 2.19–3.49 < 0.0001
Family history (Middle East) 4 2.70 1.81–4.03 < 0.0001
C‐section 4 1.08 0.99–1.17 0.0768
Breast fed as infant 2 0.76 0.49–1.17 0.2042
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3.2.1. Childhood Trauma

Childhood trauma of varying origins is well studied in the IBS literature. The presence of one or more broadly defined trauma measures via the Adverse Childhood Experiences (ACE) scale (Berens et al. 2020; Park et al. 2016; Priego‐Parra et al. 2024) and other metrics (Koloski et al. 2015), such as the Bremner Early Trauma questionnaire (Halland et al. 2014) and Childhood Traumatic Events Scale (Ju et al. 2020), had a significant effect on IBS status (pooled OR 1.61, 95% CI 1.29–2.01, p < 0.0001, n = 6) (Table 1, Figure 2). There were moderate but insignificant levels of heterogeneity (i.e., high levels of between‐study variation not just attributable to statistical chance) within this analysis (p = 0.1303, I 2 = 41.25%). Publication bias was not detected via an asymmetry test (p = 0.1773).

FIGURE 2.

FIGURE 2

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Forest plot results of childhood trauma meta‐analysis, including individual studies and pooled results of the random effects (RE) model.

When broken down into categories of specific abuse subtypes, broadly defined childhood sexual abuse (Goodwin et al. 2013; Halland et al. 2014; Ju et al. 2020; Koloski, Talley, and Boyce 2005; Park et al. 2016; Priego‐Parra et al. 2024; Romans et al. 2002; Ross 2005; Tietjen et al. 2010) was significant in regard to IBS risk (pooled OR 1.57, 95% CI 1.14–2.18, p = 0.0061, n = 9) (Table 1, Figure 3a). There was high and significant heterogeneity (p = 0.0008, I 2 = 70.5%), and Egger's test detected publication bias (p = 0.0241). Sub‐meta‐analyses were thus conducted to better understand this heterogeneity, looking at both diagnosis method and study country of origin. When using only studies that diagnosed IBS via the Rome IV criteria to improve comparability across studies, sexual abuse was still significant (pooled OR 1.90, 95% CI 1.35–2.67, p = 0.0002, n = 4), with no heterogeneity (p = 0.5941, I 2 = 0%) (Table 1, Figure 3b). Studies that used self‐reported IBS status or a gastroenterologist's diagnosis via medical records were insignificant for IBS status, with significant, high heterogeneity (p = 0.0085, I 2 = 70.70%). Sub‐setting by study country of origin did not reduce heterogeneity.

FIGURE 3.

FIGURE 3

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(a) Forest plot results of childhood sexual trauma meta‐analysis, including individual studies and pooled results of the random effects (RE) model. (b) Forest plot results of the subset childhood sexual trauma meta‐analysis using only studies which diagnosed via the Rome or Manning criteria method, including individual studies and pooled results of the RE model.

Broadly defined physical abuse (Goodwin et al. 2013; Halland et al. 2014; Ju et al. 2020; Koloski, Talley, and Boyce 2005; Longstreth and Woldetsadick 1993; Park et al. 2016; Priego‐Parra et al. 2024; Romans et al. 2002; Tietjen et al. 2010) was a significant predictor following a similar pattern to sexual abuse (pooled OR 1.37, 95% CI 1.04–1.82, p = 0.0275, n = 9) (Table 1, Figure 3a). Heterogeneity was high and significant (p = 0.0038, I 2 = 64.74%), though publication bias was not detected via an asymmetry test (p = 0.7744). Again, sub‐meta‐analyses were conducted to better understand this heterogeneity. When using only studies that diagnosed IBS via the Rome IV or Manning criteria to improve comparability, physical abuse was still significant (pooled OR 1.56, 95% CI 1.04–2.34, p = 0.03, n = 5), with insignificant but moderate heterogeneity (p = 0.0793, I 2 = 52.14%) (Table 1, Figure 4b). The pooled effect for studies that used self‐reported IBS status or a gastroenterologist's diagnosis via medical records was insignificant. Again, sub‐setting by study country of origin did not reduce heterogeneity.

FIGURE 4.

FIGURE 4

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(a) Forest plot results of childhood physical trauma meta‐analysis, including individual studies and pooled results of the random effects (RE) model. (b) Forest plot results of the subset childhood physical trauma meta‐analysis using only studies which diagnosed via the Rome or Manning criteria method, including individual studies and pooled results of the RE model.

Neither verbal (Koloski, Talley, and Boyce 2005; Longstreth and Woldetsadick 1993) nor emotional abuse (Halland et al. 2014; Park et al. 2016; Priego‐Parra et al. 2024; Tietjen et al. 2010) had a significant effect on IBS status (Table 1). Emotional abuse showed no signs of asymmetry or publication bias (p = 0.1028). Verbal abuse could not be tested due to sample size.

Three other traumatic childhood events qualified for meta‐analysis: parental divorce, family death, and a history of family mental illness. Family death (Ju et al. 2020; Priego‐Parra et al. 2024) and parental divorce (Goodwin et al. 2013; Ju et al. 2020; Park et al. 2016) did not have a significant effect on IBS (Table 1). Parental divorce showed no signs of asymmetry indicating publication bias (p = 0.3492), and due to sample size, family death could not be tested. A presence of family mental illness (Knight et al. 2015; Park et al. 2016; Priego‐Parra et al. 2024; Waehrens et al. 2018), including anxiety and depression, was significant for IBS risk (Table 1). There was high and significant heterogeneity (p < 0.0001, I 2 = 85.84%), though publication bias was not detected via Egger's test (p = 0.0667).

3.2.2. Family History

Having a family member with IBS (Akbayram 2021; AlButaysh et al. 2020; Alkalash et al. 2023; Hafiz et al. 2023; Kalantar et al. 2003; Koloski et al. 2015; Locke et al. 2000; Ramírez Aranda et al. 2024; Raslau et al. 2016; Saito et al. 2008, 2010; Waehrens et al. 2018) significantly increased the risk of adult IBS (pooled OR 2.17, 95% CI 1.89–2.49, p < 0.0001, n = 11; Table 1) There was significant, high heterogeneity within these results (p < 0.0001, I 2 = 79.81%) (Figure 5a), and publication bias was detected via Egger's test (p = 0.0243). To better understand the source of this heterogeneity, we conducted sub‐meta‐analyses. Limiting our analysis to only studies conducted in the United States showed significant risk of adult IBS (pooled OR 2.77, 95% CI 2.19–3.49, p < 0.0001, n = 4) and no heterogeneity (p = 0.8453, I 2 = 0%) (Figure 5b). Expanding this to North America and including the study conducted in Mexico maintained a significant effect size, though was the source of moderate heterogeneity (p = 0.0434, I 2 = 59.30%). Studies conducted in the Middle East (Saudi Arabia and Turkey) also showed significant risk of adult IBS (pooled OR 2.70, 95% CI 1.81–4.03, p < 0.0001, n = 4) and moderate but insignificant heterogeneity (p = 0.0273, I 2 = 67.23%) (Figure 5c). Sub‐setting by diagnosis method did not reduce heterogeneity.

FIGURE 5.

FIGURE 5

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(a) Forest plot results of family history meta‐analysis, including individual studies and pooled results of the random effects (RE) model. (b) Forest plot results of the subset family history meta‐analysis using only studies in the United States, including individual studies and pooled results of the RE model. (c) Forest plot results of the subset family history meta‐analysis using only studies in the Middle East, including individual studies and pooled results of the RE model.

3.2.3. Birth Factors

When analyzed via meta‐analysis, birth related factors had no significant effect on IBS risk. While birth by Cesarean section was a significant predictor for IBS in some studies (Olén et al. 2018; Waehrens et al. 2018), others showed no significant relationship (Koloski et al. 2015; Raslau et al. 2016). A meta‐analysis conducted on these studies showed no significant effect (pooled OR 1.08, 95% CI 0.99–1.17, p = 0.0768, n = 4) (Table 1). Publication bias was not detected via a test for asymmetry (p = 0.2376). Only two studies investigated the effects of breastfeeding, and both were insignificant (Koloski et al. 2015; Raslau et al. 2016). The meta‐analysis for these papers was also insignificant (pooled OR 0.76, 95% CI 0.49–1.17, p = 0.2042, n = 2) (Table 1).

4. Discussion

We set out to assess the developmental origins of IBS by testing behavioral, environmental, and proxies for genetic exposures during critical developmental periods and their association with adult IBS status. Childhood environmental and behavioral factors, particularly childhood trauma, demonstrably impact adult IBS status, while family studies suggest a familial, and potentially genetic, element (Bengtson et al. 2006). Rather than view these as competing, either environmental or genetic causes of illness, we suggest this meta‐analysis provides support for the idea that IBS may be driven by early life gene–environment interactions, warranting a life course approach rather than the previous emphasis on adult risk factors and illness.

The largest pooled effect size in this meta‐analysis, and most significant predictor of IBS, was having a family member with IBS. The strong association between family history and IBS was surprising, as studies have found variation in IBS to be largely driven by environmental, rather than genetic, factors (Mahurkar‐Joshi and Chang 2020; Mohammed et al. 2005; Talley 2005). One explanation for this pattern is that it is attributable to shared family environments, meaning IBS does not run in families because of a genetic mutation, but rather, a similar exposure to environmental risk factors. Future work, comparing both family members who share environments (i.e., mothers, fathers, siblings), and those who did not share environments (i.e., cousins), would help to better understand this relationship.

Many elements of childhood exposure and IBS have not been thoroughly examined, as this systematic review makes clear, but one well‐researched childhood domain is childhood abuse. Childhood adverse experiences and trauma measures had a significant association with adult irritable bowel status. Physical and sexual abuse types were particularly significant predictors of IBS, though verbal and emotional abuse were not. One possible explanation for this discrepancy is that physical and sexual abuse may have longer lasting effects, particularly through somatization, that those who are verbally and emotionally abused may not experience (Koloski, Boyce, and Talley 2006; Lackner, Gudleski, and Blanchard 2004; Reilly et al. 1999). These somatic, traumatic childhood events may disrupt early digestive development or microbiome formation, leading to IBS via a dysregulated brain–gut axis. This would support the predictions made under the DOHaD framework, suggesting that early life exposures disturb physical development and lead to adverse, downstream health consequences in adulthood.

Adopting a DOHaD approach, considering the dynamic ways in which the interplay of environments and genes may influence disease status, provides a framework to interpret these family history and childhood trauma findings jointly. While shared environments likely play a role in familial IBS status, there may be an intergenerational component, caused by maternal exposure and epigenetic modifications. This meta‐analysis shows that the developmental origins of disease go beyond childhood and birth conditions, and may even reflect maternal life events, especially maternal trauma (Ahmad et al. 2022; Kaliush et al. 2023). Adverse childhood experiences (ACEs) for the mother can cause childhood behavioral issues, lowered birth weight, and even increase the odds of mental illness among her children (Ahmad et al. 2022; McDonnell and Valentino 2016). Childhood trauma also is demonstrated to cause epigenetic modifications, such as DNA methylation, both maternally and paternally (Nie et al. 2022). Since childhood trauma is an identified risk factor for IBS, and it also may run in families, we hypothesize that IBS may be caused by a gene–environment interaction during childhood in response to trauma, which may in some cases pass to the next generation. This introduces exciting potential for future work, looking at parental ACEs and IBS status alongside offspring IBS status. With this in mind, we may better disentangle the potential developmental, environmental, and genetic risks for adult IBS to determine if there is indeed a family predisposition for IBS following trauma.

4.1. Sample Variation

Several investigated variables showed high rates of heterogeneity, or high levels of between‐study variation not just attributable to statistical chance. Much of this variation was resolved when subset by relevant study parameters. Diagnosis method had the largest impact on the significant effects of abuse; Rome methods of diagnosis reduce heterogeneity to insignificant, null levels while maintaining significant effects on IBS status. When other methods were used, for instance self‐reported IBS status or IBS status as determined by a gastroenterologist and reported in medical records, these types of abuse were not significant predictors for IBS. In other studies where sub‐meta‐analyses were conducted based on diagnostic method, there was no difference in the pooled effect of certain risk factors. Therefore, we conclude that diagnostic method may be a source of variation in the interpretation of risk factors, and that a consistent, criteria‐based method may minimize this variation and be more reliable in future epidemiological studies.

While country of study origin did not reduce variation in studies investigating childhood abuse, it did for family history studies. Studies conducted in the United States had 0% heterogeneity, meaning all variation was due to chance. Similarly, studies conducted in the Middle East had insignificant heterogeneity. One study was conducted in Mexico and two in Sweden and adding these to either subset increased heterogeneity to significant amounts. Due to the sample size of all country of origin subsets, however, it is unclear whether country of origin has a meaningful effect on the results, and further work is needed.

4.2. Using Evidence Synthesis to Explore Developmental Questions

This meta‐analysis was limited by the availability of data. While we uncovered a robust set of papers following the systematic review, many of the collected variables could not be pooled for a meta‐analysis. This introduced limitations in determining the full effect of certain variables of interest on adult IBS status. While additional childhood variables were explored (see Appendix S3), this was either qualitatively, or an analysis conducted on two papers, which is not usually considered reliable. While publication bias was present for studies investigating family history and childhood sexual abuse, most of the variables we investigated did not show signs of publication bias. This indicates that, instead of a file drawer effect indicating researchers may have been unable or unwilling to publish null results, the limited data available may simply be due to the limited amount of work being conducted in this space.

Furthermore, due to the limited number of papers per variable, we had to pool studies with mixed diagnosis methods, mixed study types, or mixed control types, all contributing toward the heterogeneity of the findings, however we did subset studies when possible. Finally, while we used raw data and unadjusted values when possible and available, some studies only provided adjusted odds ratios and confidence intervals.

A meta‐analysis exploring developmental questions, conducted on largely cross‐sectional data, has inherent limitations and challenges. Ideally, the research question of whether IBS is a disease of developmental origins would be best conducted on a longitudinal sample, following a cohort over time (perhaps even as early as pregnancy), documenting exposures and tracking health outcomes. Yet, this gold standard of research is resource‐ and time‐intensive, necessitating other preliminary methods. Evidence synthesis faces many general limitations, outlined above, and our evolutionary interpretations are restricted to the existing literature that is available. Despite these limitations, this approach provides a preliminary answer to questions regarding the developmental origins of IBS by merging two sets of existing literature (family history and childhood trauma) within a guiding theoretical framework. Previously, these two risk factors have been considered separately. While this study does not confirm IBS as an illness with developmental origins, it does demonstrate the relevance of both genetic and environmental components of the illness, as well as posit their potential interaction.

5. Conclusion

A systematic meta‐analysis of all literature related to childhood exposures and adult IBS status, found that childhood trauma and family history of IBS were the two most well‐researched, and statistically significant, predictors. Birth factors, including breastfeeding or birth pathway, were not significant predictors of IBS. Other environmental exposures have yet to be thoroughly researched enough to analyze via meta‐analysis, and more work is needed on this front. Family history and childhood trauma measure both genetic and environmental contributions to IBS during development, supporting our hypothesis that IBS is an illness with developmental origins. These results suggest IBS is potentially exacerbated via gene–environment interactions. This evidence synthesis is a vital first step toward illustrating this potential interaction, indicating a strong need for further research investigating the impact of epigenetic changes and environmental exposures during childhood on IBS status, expanding beyond the heavy emphasis on adult exposures and disease that currently characterizes most of the IBS literature.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Appendix S1.

AJHB-37-e24209-s003.docx (14.4KB, docx)

Appendix S2.

AJHB-37-e24209-s001.xlsx (15.5KB, xlsx)

Appendix S3.

AJHB-37-e24209-s002.docx (26.1KB, docx)

Table S1. Bibliographic and study information for papers used in meta‐analysis.

AJHB-37-e24209-s004.docx (25.1KB, docx)

Acknowledgments

The authors extend their gratitude to Heather K. Moberly, Penn State's Agricultural and Veterinary Librarian, who consulted with us for our literature search. We would also like to thank various friendly reviewers for their comments on this paper, including Laura Perez, Kofi Clarke, Joon Hwang, Nafi Mohammad Ali, Dithapelo Medupe, and Sojung Baek. The PRISMA flowchart was created with BioRender.com.

Funding: The authors received no specific funding for this work.

Data Availability Statement

The data that support the findings of this study are available in the Supporting Information of this article.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Appendix S1.

AJHB-37-e24209-s003.docx (14.4KB, docx)

Appendix S2.

AJHB-37-e24209-s001.xlsx (15.5KB, xlsx)

Appendix S3.

AJHB-37-e24209-s002.docx (26.1KB, docx)

Table S1. Bibliographic and study information for papers used in meta‐analysis.

AJHB-37-e24209-s004.docx (25.1KB, docx)

Data Availability Statement

The data that support the findings of this study are available in the Supporting Information of this article.

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