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Risk factors for developing irritable bowel syndrome: systematic umbrella review of reviews

BMC Medicine volume 23, Article number: 103 (2025) Cite this article

Abstract

Background

Irritable bowel syndrome (IBS) is a debilitating disorder affecting 4–9% of the global population. It is a multifaceted disorder with complex and varied causes. This review aims to consolidate the evidence regarding IBS risk factors by examining existing systematic reviews and meta-analyses, covering potential genetic, immunological, psychological, and dietary causes.

Methods

Systematic literature searches were conducted in MEDLINE, Embase and Cochrane library databases. Study selection and data extraction were conducted independently by four authors, with discrepancies resolved by consensus with a senior author. Systematic reviews examining risk factors of IBS development were eligible for review. Results were narratively synthesized. Quality of reviews were analysed using AMSTAR 2, and evidence were appraised using GRADE methodology.

Results

A total of 69 systematic reviews were included in this study. Most reviews were of “critically low” quality, while the remaining were “low” quality. Common shortcomings included the absence of a list of excluded studies with justifications for their exclusion and inadequate consideration of the risk of bias in individual studies. Eight major categories of risk factors for IBS identified were as follows: dietary, genetic, environmental, psychological, gut microbiome, socio-economic, physiological, and pathological, albeit overlaps exist. The most frequently reported risk factors for IBS development were female gender and anxiety disorders, with overall GRADE evaluation of “low”; depression and gastroenteritis, with overall GRADE evaluation of “moderate”.

Conclusions

Clinical practice should prioritize recognition of these risk factors. Future reviews should improve their reporting of results based on the PRISMA guidelines, to enhance the quality of research in this field.

Protocol registration

PROSPERO CRD42023493739.

Peer Review reports

Background

Irritable bowel syndrome (IBS) is a disorder of the gut-brain axis diagnosed through the symptom cluster outlined in the ROME IV criteria [1, 2]. It is an exceedingly common condition, affecting some 4–9% [3] of the global population, and with significant adverse effects and impediments. Research has consistently shown that IBS reduces the quality of life related to health [4] and contributes to workplace absenteeism at a societal level [5], underlining its economic burden [6]. Additionally, the global trend towards adopting a Western diet and lifestyle [7] is expected to increase the incidence of IBS. Given its rising prevalence [7] and the chronic nature of this condition [8], this necessitates further research into the risk factors for new-onset IBS to develop preventive measures against the onset of the condition.

At present, the causes of IBS are varied, complex, and incompletely understood [9]. Research continues to explore a broad range of risk factors, including genetic [10], immunological [11], psychological [12], and dietary elements [13]. Recent years have seen burgeoning interest in understanding how the gut microbiota [14], the interactions between the gut and the brain [15], and gastrointestinal motility [16] contribute to the development of IBS. Furthermore, the field of exposomics [17, 18], which examines the influence of environmental factors on disease development, is shedding new light on new risk factors for IBS. For instance, air pollution, already linked to various health issues, is now being investigated for its potential role in altering the gut microbiome and increasing the risk of IBS in previously healthy individuals [19, 20]. The expanding body of research underscores the relevance and timeliness of an overview of systematic reviews on these topics, which would help synthesize and critique current knowledge and findings.

Addressing this gap, this study attempts a umbrella review of existing systematic reviews [21], specifically focusing on risk factors associated with the onset of IBS in individuals who were previously healthy. These findings aim to bridge the gap between research on IBS risk factors and their applications in clinical settings, enhance current preventive strategies, and inspire further investigations into this critical area.

Methods

Search strategy

We searched MEDLINE, Embase, and Cochrane library databases from database inception to November 11, 2024. This current systematic review was performed with reference to the latest Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [22], with search terms including but were not limited to “Irritable Bowel Syndrome”, “Risk Factors” and “Systematic Review”. The search strategy was developed in consultation with an information management specialist, and the full search strategy is available in the Supplementary Material (Table S1). The study protocol was prospectively registered in PROSPERO (registration number CRD42023493739).

Eligibility and selection criteria

All search results were imported into Covidence (Melbourne, Victoria, Australia) for the identification and removal of duplicates. To ensure consistency and rigour, the Covidence software was set to ensure that each article was reviewed independently by two reviewers independently at every stage, including both the title and abstract screening and the full-text review phases. For the title and abstract screening, five reviewers (FS, TOSK, ASPT, JQ, and DTL) were involved to ensure comprehensive coverage of the large number of search results and to identify a wider pool of potentially eligible studies before reaching consensus with a senior reviewer. Discrepancies at both stages were resolved through consensus with a senior author (QXN or KTHS). Only original systematic reviews of observational studies, including cohort, case–control and cross-sectional studies, or interventional studies in English or with an English translation were included. Non-systematic narrative reviews, editorials, opinion pieces and case reports were excluded from the study. Studies which investigated primary risk factors of IBS in previously healthy individuals which may include but were not limited to dietary factors, psychosocial factors, gastrointestinal infections, certain medication uses, lifestyle factors such as physical activity and sleep patterns, genetic predisposition, environmental factors and socioeconomic factors. Studies without a clear diagnosis of IBS, those that examined non-specific exposures, interventions for managing IBS, secondary risk factors (that might affect the course or management of IBS), animal studies, or those involving pediatric populations were excluded.

Data extraction and outcomes

The primary outcomes of interest in this paper include the measure of the strength of association between the defined risk factor(s) and the development of IBS, reported in relative risks (RR), odds ratios (OR), or prevalence/incidence rates in the reviewed studies. Narrative synthesis of collected data was conducted. Study characteristics, populations, risk factors examined, IBS outcome measures and key findings would be extracted from included papers, with similar risk factors being grouped together (e.g. dietary, psychological, early life exposures) across different studies. We also provided a summary of the evidence supporting each category and evaluated the strength of association with developing IBS.

Quality assessment and risk of bias

The Measurement Tool to Assess Systematic Reviews (AMSTAR2) tool was used for quality assessment and check for robustness of evidence provided in the studies included in this systematic review [23]. The AMSTAR2 tool comprises 16 items that evaluate various aspects of a systematic review’s methodology, such as the comprehensiveness of the literature search, the justification of excluded studies, the appropriateness of the methods used to synthesize results, and the assessment of the risk of bias in individual studies. This produces an overall grading of an article: high, moderate, low or critically low. To comprehensively evaluate the level of evidence for frequently mentioned risk factors, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used [24]. The GRADE framework evaluates evidence in five domains, namely: Risk of bias, inconsistency, indirectness, imprecision and publication bias.

Results

Summary of included studies

The initial search from the Embase, MEDLINE and Cochrane Library databases yielded 4903 articles. References were imported into Covidence, resulting in the automated removal of 1119 duplicates. Further screening resulted in the manual removal of 3784 articles not meeting the including criteria during the title and abstract sieve, with 101 articles remaining for full-text screening. Grey literature was also searched, identifying two articles for review, one of which was not retrievable. Finally, a total of 69 systematic reviews [2, 25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92] published between 2002 and 2024 were included. The process of literature search and article selection is summarized in Fig. 1. A summarized list of studies and their reason(s) for exclusion after full-text review is detailed in the Supplementary Material (Table S2).

Fig. 1
figure 1

PRISMA flowchart showing the study search and selection process

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Appraisal of quality of reviews

As rated using the AMSTAR2 tool, all studies were categorized as “low” (15 studies, 22%) or “critically low” (53 studies, 77%) or moderate (1 study, 1%). More than half the studies adhered to the population, intervention, comparator group, outcome (PICO) framework for research questions, explained the selection of study designs for inclusion, performed study selection and data extraction in duplicate, report sources of funding, utilize the appropriate statistical combination of results in meta-analysis, provide satisfactory explanation and discussion of heterogeneity, adequately investigate publication bias and report potential conflict of interest, including funding for the study. More than half, at least partially, adhered to having an explicit statement of review methods and reporting deviation from study protocol, have a comprehensive literature search strategy, describe included studies in adequate detail and use a satisfactory technique for assessing risk of bias (ROB) in individual studies. However, the most common critical flaws were not prospectively registering their study protocols, providing a list of excluded studies and justifying the exclusions and providing an account for the ROB in individual studies when interpreting/discussing the results of the review. The details of the AMSTAR2 results of included reviews are explained in Table 1.

Table 1 AMSTAR2 quality assessment for reviews included
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Significant factors across reviews

The included reviews have analysed the literature across some 30 databases, with most studies analysing literature from PubMed, MEDLINE, Embase, Cochrane, Web of Science, Scopus and Google Scholar. Collectively, the literature was searched from inception to 2023. Most of the reviews analysed purely observational studies, while three reviews [27, 54, 55] included interventional studies in their analysis. The risk factors identified from the included reviews have been grouped into eight common themes listed below. The summary of findings is shown in Table 2.

Table 2 Summary of included reviews and their findings
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Dietary factors

High ultra-processed food consumption [28] and fatty food [40] were reported as significantly associated with IBS development. Alcohol consumption [30, 50, 79] were reported as risk factors of IBS. Food allergy [87] was also reported as a common risk factor.

Genetic factors

Genetic factors are being female [2, 30, 40, 45, 47,48,49, 51, 79, 81], having a family history of IBS [49, 50, 87] and TNFSF15 polymorphism [82]. Conflicting evidence surrounds 5HTTLPR as most studies [26, 72, 80] did not report it as a risk factor, the SLC6A4 [82] polymorphism is significantly associated with IBS development. GNB3 C825T [41, 59, 82], IL-10 rs1800871 [62, 82], IL-10 rs1800870 [62], IL-10 rs1800872 [62] and TNF-α rs1800629 [82] polymorphisms were found not to be risk factors for IBS. Conversely, COMT rs4680 [82] and IL-10 rs1800896 [82] were found to be significantly associated with decreased IBS development.

Environmental factors

Smoking [87], air pollutants [50, 89], sharing a bedroom up to age 5 years old [89], raising herbivorous pets [50, 89] or history of pet ownership [89], poor sanitation [89] and shorter period of breastfeeding [50] were found to have significant association with IBS development.

Psychological factors

Anxiety disorders [30, 40, 45, 67, 79, 87], depression [30, 40, 45, 58, 67, 79, 87], neuroticism [45], somatization at the time of infectious enteritis [45], stress [30, 40, 87], binge-eating disorder, anorexia nervosa and eating disorders not otherwise specified [38] were found to have significant association with IBS development. Post-traumatic stress disorder (PTSD) [57], history of past trauma [90] and history of childhood sexual abuse [85] were found to be a significant risk factor of IBS.

Gut microbiome

Clostridioides difficile (C. difficile) [64] infection for longer than 7 days was found to be a significant risk factor for IBS. A history of colonic spirochetosis [33], antibiotic exposure [45, 50], infective gastroenteritis [30, 37, 45, 50, 71, 89], Blastocystis spp. [63, 73], C. difficile, Salmonella spp., Shigella spp., Escherichia coli (E. coli) [70] and Helicobacter pylori [88] were found to have significant associations with IBS development. Levels of Bifidobacterium spp. [73, 83] were reported to be significantly lower in patients with IBS compared to patients without IBS. Severe acute respiratory syndrome coronavirus 2 (SARS-COV2) was also associated with a higher incidence of IBS [53]. A significant proportion of the IBS population was also observed to have gut dysbiosis [89].

Socio-economic factors

Child abuse, childhood living density of less than one person per room, parental deprivation, childhood affluence [29, 50], social learning of illness behaviours, parental reinforcement (rejection, hostility, parental punishment, over interference, overprotection), parental coping strategies (family history of mental illness/alcohol, substance use problems), psychological distress during childhood (e.g. parental history of anxiety/ depression/somatization, family stress, childhood, introverted personality) and children with mothers who were young (less than 20 years old), divorced or widowed, and with an education of 10 to 14 years [50] were reported as risk factors of IBS. Shift work [47, 74], students in medical majors [40, 79], postgraduate students [79], poor sleep quality [47] and frequent use of healthcare [30] had significant associations with IBS development. High workload, low income and occupation types were commonly reported features of IBS populations [87].

Physiological factors

Low birth weight [29, 50] and increased intestinal permeability [91] were found to have significant positive association with IBS. There is inconclusive evidence of increasing age [2, 30, 45, 48, 71, 81, 87] as a risk factor for IBS.

Pathological factors

Gastroesophageal reflux disease (GERD) [32, 55, 87], migraine [30, 78], vitamin D deficiency [79], the presence of IgM antibodies against gonadotropin hormone-releasing hormone (GnRH) and GnRH receptor [54], preschoolers with a history of atopy/allergy [50], women with endometriosis [65], asthma [30], diabetes [30, 87], previous abdominal operation and exposure to coldness and fatigue [50] were found to be significant risk factors for IBS development. Temporomandibular joint (TMJ) disorder [30, 77], fibromyalgia syndrome [2, 30, 77], visceral hypersensitivity [2, 38], food hypersensitivity [40, 60], sleep disorders [30, 40], spondyloarthropathy [86], chronic liver disease [30], a history of dysentery [45], restless leg syndrome [36], having diarrhoea for more than 7 days [45] and abdominal pain [45, 87] had a significant association with IBS development. A history of chronic disease was also reported as a common risk factor for IBS development [87].

Empirical evidence and GRADE evaluation

Amongst the risk factors mentioned, female gender, anxiety disorder, depression and gastroenteritis were the most frequently mentioned across reviews. Depression and gastroenteritis were supported with relatively higher evidence, with a “moderate score” when assessed using GRADE. Depression had an association magnitude ranging from RR 1.90 to RR 5.57 and OR 1.49 to OR 2.15, while gastroenteritis had an association with magnitude of RR 3.8 and OR 5.86 to OR 7.3 reported. Female gender and anxiety disorder were supported by relatively lower levels of evidence when assessed by grade, with a “low” score attributed to both. Across reviews, female gender had an association of magnitude OR 1.36 to OR 2.29 while anxiety disorder has an association magnitude of RR 2.38 and OR 1.97 to 2.35. The results of GRADE evaluation for the aforementioned factors are summarized in Table 3.

Table 3 Summary of the main findings as per GRADE
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Discussion

This review of reviews provides an overview of the current evidence regarding the risk factors for the IBS development. Eight overarching categories of risk factors were identified across the 69 included systematic reviews in this study, as illustrated in Fig. 2. Amongst the various risk factors mentioned, four were frequently identified across the included reviews, supported by robust evidence for its position as a risk factor of IBS development: female gender, anxiety disorder, depression and gastroenteritis.

Fig. 2
figure 2

Overview of risk factors for IBS development based on existing systematic reviews

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IBS has long been associated with female gender, with an estimated 2–2.5:1 male-to-female ratio for IBS development [93]. While the exact pathophysiology has not been ascertained, a common mechanistic pathway emphasized across literature are the hormonal differences between both genders [94]. In addition to the modulatory effect of progesterone on the 5-hydroxytrptamine (5-HT) system that controls peristalsis [95], estrogen and progesterone have an inhibitory effect on smooth muscle contraction [94]. Consequently, IBS, especially the constipation variant (IBS-C), has a higher incidence in women compared to men [96]. While the interplay between gender and IBS development highlights the importance of this risk factor, the association with worse outcomes further compels further effort in preventing IBS development within this patient group. Fan et al. reports higher IBS symptoms score and lower IBS-quality of life (IBS-QOL) scores experienced in female patients [97]. Cain et al. also reports more somatic symptoms experienced by women afflicted with IBS, including joint and muscle pain [98]. However, despite worse outcomes in female populations, abdominal concerns are more likely to be minimized by healthcare professionals [99]. Windrim et al. reports the internalization of normative views regarding women’s pain of lower concern as a possible explanation. Given its significance as a risk factor and outcome modulator, further emphasis on this risk factor is necessitated in clinical guidelines aimed at prevention of IBS development.

A bi-directional association has been established between both mental conditions and IBS development [45, 100]. Mechanistically, two pathways have been described. The increased release of corticotropin-releasing hormone (CRH) in response to stress [12] in anxiety and depression causes hyperactivation of the hypothalamic–pituitary–adrenal axis and autonomic nervous system, consequently altering gut motility and increasing visceral sensitivity [101]. Stress-induced microbiota dysbiosis also causes gut barrier dysfunction and immune activation, further contributing to gut motility abnormalities [102]. The impact of IBS onset on individuals with anxiety and depression is extensive, as they are more likely to experience reduced quality of life from the symptoms of IBS and exhibit reduced treatment adherence compared to those without anxiety or depression [100, 103]. However, patients with undiagnosed anxiety and depression who display symptoms of IBS are only offered central neuromodulators and psychological therapies when they fail to respond to pharmacotherapy for symptomatic management of IBS [104]. The resultant delay in resolution of IBS symptoms may cause patient dissatisfaction and inadvertently lead patients to seek alternative therapies which lack robust evidence, thereby increasing the risk of harm [102]. This underscores the need for more stringent screening of comorbid anxiety and depression disorders in the diagnosis of IBS to allow for accurate choice of pharmacotherapies and early referral for psychotherapies where required [105, 106].

In agreement with literature, acute gastroenteritis is a common risk factor amongst various systematic reviews, with reports approximating 10% pooled prevalence [107] of post-infectious IBS (PI-IBS) in acute gastroenteritis patients. Although the exact mechanism is poorly understood, common pathophysiological hypotheses include prolonged imbalance of host immune cells and mediators that affect inflammatory homeostasis, disruption to the intestinal mucosal barrier and intestinal dysbiosis [108]. While any pathogens may potentiate PI-IBS, notable pathogens strongly associated with PI-IBS include as follows: Norovirus [109] and Rotavirus [110], E. coli [111], Salmonella spp. [112], Campylobacter spp. and Giardia duodenalis (G. duodenalis) [113]. Despite being a common risk factor, gastroenteritis is however, an easily treatable cause of IBS development. Epidemiological data would prove crucial in capitalizing on this information for effective prevention and treatment considering inter-region difference in infective gastroenteritis pathogen. In addition to gastroenteritis, a patient’s gut microbiota also plays a role in IBS development. Specifically, changes in prevalence of indigenous species such as Faecalibacterium spp., Lactobacillus spp. and Bifidobacteria spp. have been linked to IBS development [73, 114]. As probiotics can modulate the composition of gut microbiota, this has resulted in the recent interest for probiotic trials of IBS relief observed in literature [115, 116].

Based on the findings of this study, the authors of this study suggest that future systematic reviews on this topic strongly adhere to the tenets of systematic reviews as outlined by PRISMA-P guidelines. In particular, item 16b and accounting for the biases in the discussion (part of 23b) are requirements that current reviews tend not to fulfill. Furthermore, other requirements, such as 14, 18 and 24a-c, were only partially met. This may be attributed to the multi-faceted nature of the requirement. Future studies should take more care in adequately addressing these criteria. To ensure quality of published literature, it is advised that journals actively require a protocol checklist, ideally the PRISMA-P checklist, to be submitted for peer review. In agreement with the current stance on study quality [117], adherence to such reporting standards should also have more weightage in a journal’s consideration for publication of the report.

To the author’s best knowledge, this study presents the first review of reviews to investigate the current evidence of risk factors for IBS development. The findings from this study were reported according to replicable methodology, which adhered to the PRISMA guidelines for systematic reviews [22], recent recommendations by Gates et al. [118] and published literature. The authors of this study also acknowledge the current limitations of this review. Review of reviews focus on published systematic reviews and meta-analyses; thus, more recent studies not identified in original reviews may not have been included in this umbrella review. Secondly, a loss of granularity is apparent in some of the findings listed above, for example the lack of clarity regarding the dose response of specific risk factors including air pollution. Lastly, the evaluation of article quality reveals low adherence to professionally accepted guidelines in several of the systematic reviews and meta-analyses reviewed. When evaluated holistically using the GRADE evaluation model, the evidence ranged between low to moderate for the major risk factors identified in this review. In view of the current limitations, the authors of this review urge the readers to interpret the presented findings with caution.

Conclusions

This umbrella review identified eight overarching categories of risk factors for IBS, of which female gender, anxiety, depression and gastroenteritis were supported by comparatively more robust evidence. While this review attempts to further the understanding regarding the significant risk factors for the development of IBS and the current evidence landscape, the multi-factorial nature of IBS demands continued research. Given that several reviews did not satisfy the good practices and recommendations for methodology as outlined by the PRISMA guidelines [22], there is also a need for caution when interpreting the data contained within the current reviews. The findings of this study also urge stronger adherence to established guidelines for the methodology of future research conducted in this area.

Data availability

This study is a systematic review and no original data were generated. All data analyzed in this study were obtained from publicly available sources, specifically MEDLINE, Embase, and the Cochrane Library. These databases are accessible through institutional or individual subscriptions.

Abbreviations

5-HT:

5-Hydroxytrptamine

CRH:

Corticotropin-releasing hormone

GERD:

Gastroesophageal reflux disease

GnRH:

Gonadotropin hormone-releasing hormone

IBS:

Irritable bowel syndrome

IBS-C:

Irritable bowel syndrome-constipation variant

IBS-QOL:

Irritable bowel syndrome-quality of life

OR:

Odds ratio

PICO:

Population, Intervention, Comparator Group, Outcome

PI-IBS:

Post-infectious irritable bowel syndrome

PTSD:

Post-traumatic stress disorder

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

RR:

Relative risk

ROB:

Risk of bias

TMJ:

Temporomandibular joint

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  1. Farisah Sulaimi, Timothy Sheng Khai Ong, and Ansel Shao Pin Tang have contributed equally and share co-first authorship for this manuscript.

Authors and Affiliations

  1. School of Medical Sciences, Wallace Wurth Building, University of New South Wales, Sydney, NSW, Australia

    Farisah Sulaimi

  2. NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Timothy Sheng Khai Ong, Ansel Shao Pin Tang, Jingxuan Quek, Renish M. Pillay, Damien Tianle Low, Charisse Kai Ling Lee & Kewin Tien Ho Siah

  3. Division of Gastroenterology & Hepatology, University Medicine Cluster, National University Hospital, Singapore, Singapore

    Kewin Tien Ho Siah

  4. NUS Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore

    Qin Xiang Ng

  5. SingHealth Duke-NUS Global Health Institute, Duke-NUS Medical School, Singapore, Singapore

    Qin Xiang Ng

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All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted. No writing assistance was obtained in the preparation of the manuscript. The manuscript, including related data, figures and tables has not been previously published, and the manuscript is not under consideration elsewhere. All authors read and approved the final manuscript. Conceptualization and Design: KTHS, QXN. Acquisition of Data: FS, TSKO, ASPT, JQ, RMP, DTL, KTHS, QXN. Analysis and Interpretation of Data: FS, TSKO, ASPT, JQ, RMP, DTL, KTHS, QXN. Writing – original draft: FS, TSKO, ASPT, JQ, RMP, DTL, KTHS, QXN. Writing – review & editing: FS, TSKO, ASPT, JQ, RMP, DTL, KTHS, QXN. Supervision: KTHS, QXN. All authors reviewed the manuscript.

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Sulaimi, F., Ong, T.S.K., Tang, A.S.P. et al. Risk factors for developing irritable bowel syndrome: systematic umbrella review of reviews. BMC Med 23, 103 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12916-025-03930-5

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