Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease characterized by altered bowel habits, abdominal discomfort or pain, and abdominal distension, without obvious structural or biochemical abnormalities (1) or organic etiology (2). A meta-analysis with 23 studies (n = 74,763) revealed that the prevalence of IBS was 6.5% in the general population in China (3). Though the pathophysiology is still unclear, IBS has been proved to be associated with multiple factors including abnormal gastrointestinal motility, visceral sensory abnormality, abnormal brain-gut regulation, inflammation, gastrointestinal infection, and stressful life events, etc. (4–6). Furthermore, recent evidences supported the negative psycho-influences to be the key role of the biopsychosocial model of IBS (4, 7–9). For instance, a meta-analysis showed the high rates of anxiety symptoms (39.1%) and disorders (23%), depression symptoms (28.8%) and disorders (23.3%) in IBS patients (10). Throughout the years, various criteria including the Manning criteria, the Rome I, Rome II, Rome III and Rome IV criteria, have been applied for diagnosis of IBS. Amongst them, the Rome III criteria (11) and Rome IV criteria (12) are the most commonly used currently.

University students are more likely to experience IBS–varied from 1.18% (13) to 33.3% (14) in China, might due to the psychological problems, unhealthy lifestyles, and a low level of health literacy (15). For instance, they are more prone to suffer from anxiety and depression symptoms, because of difficulties in terms of academic pressures, occupational choices, interpersonal conflict, and life goal decisions (16), which could cause gastrointestinal disorders through the brain-gut axis mechanism (17). A lack of physical exercise, irregular eating habits (i.e., not having breakfast), smoking, and drinking behaviors have also been found common in university students (18), which may contribute to the risk of IBS in this population. Moreover, due to various clinical examinations and constant medical treatment, IBS has been proved to be linked to physical problems like headache, chronic back or neck pain and diabetes (19), mental disorders like anxiety and depression (20) and obsessive-compulsiveness (21), sleep disorder (22), poorer academic achievements (23), lower quality of life (24, 25), social embarrassment due to diarrhea (a symptom of IBS) which restricts the patients being near a bathroom (26), and higher economic cost (24).

There has been a growing number of studies on IBS in Chinese university students, but the prevalence of IBS varied widely in existing studies. Precise epidemiological figures related to IBS prevalence are fundamental to inform preventive strategies in an evidence-based way. This study aimed to quantitatively evaluate the prevalence of IBS and its associated factors among Chinese university students via systematic review and meta-analysis.

To the best of our knowledge, this is the first systematic review and meta-analysis to estimate the pooled prevalence of IBS among Chinese university students, including 22 studies with 33,166 subjects. The major findings are: (1) the pooled prevalence of IBS among Chinese university students was 11.89% (95% CI = 8.06%, 16.35%); (2) the prevalence of IBS was significantly associated with educational level, gender, major, region, survey year, diagnostic criteria, anxiety, depression, drinking, smoking, and sleep disorders.

The prevalence of IBS in our study was approximate to that of 10.9% in American university students (56) and 10.7% in Japanese university students (57), but higher than that in Korean college students (5.7%) (58), lower than that in Pakistan college students (34%) (59). The possible explanations might be the difference in culture, diet habits, physical characteristics, academic and socioeconomic stress across countries.

Students with psychological disorders such as anxiety and depression had an increased likelihood of IBS comorbidity compared to those without. The link between psychosocial factors and gastrointestinal function (motility, sensation, inflammation) could be explained by the brain-gut axis (17). Specifically, this implies a bidirectional connection system between the gastrointestinal tract and the brain, through neural, neuroimmune and neuroendocrine pathways. In this model, individuals with increased central nervous system (CNS) arousal such as those with anxiety and depression, could experience gastrointestinal distress and increased gastrointestinal motility via CNS-mediated sympathetic outflow (60), leading to the destruction in the intestinal mucosal barrier (61) and the change of transport in the small intestine and even the entire gastrointestinal tract (62) and, resulting in gastrointestinal symptoms (cramping and pain, etc.) of IBS.

Our study found that the prevalence of IBS was higher among female students. This discrepancy could be attributed to several factors. First, the difference in the secretion of sex hormones contributes to the gender difference in the modulation of IBS. For example, androgens, higher in males, possibly could reduce visceral pain through enhancing TRPM8 expression and/or activity (63). TRPM8 is suggested to possess anti-nociceptive roles in the intestine (64) and ligands of TRPM8 such as peppermint are believed to possess analgesic effects in IBS patients (65, 66). As for females, the higher level of hormones like estrogen contributes to the development of IBS. It is reported that estrogens inhibit colonic smooth muscle contraction via a non-genomic mechanism involving cell membrane coupling (67), leading to the higher occurrence of IBS-related symptoms including abdominal distension, bloating, infrequent stools and hard stools (68). Estrogens promote activation of mast cells (68), which are found to be associated with IBS through increasing intestinal nerve sensitization (69). Second, for females, increased prostaglandins during the menstrual cycle could induce diarrhea syndrome, one of the IBS symptoms, through enhanced intestinal secretion and altered electrolyte absorption (70). Third, women are more vulnerable to experience life stress, anxiety, and depression symptoms (71, 72), which are associated with a higher incidence of IBS.

In terms of majors, a higher prevalence of IBS was estimated in the medical students. This might be due to the long length of schooling, high load from the academy and clinical practice, high level of psychological stress exposure like severe anxiety and depression (73) and sleep disturbances (74). It was proved that the stress was associated with the development of IBS through stimulating the hypothalamic-pituitary-adrenal (HPA) axis and triggering the release of some substances including corticotrophin-releasing factor (CRF), adreno-cortico-tropic-hormone (ACTH), and cortisol, which affect gut function through the composition and the growth of microbiota, and stimulate the sympathetic nervous system (SNS) (75). Sleep disorder, such as insomnia, was associated with a 24-h increase of ACTH and cortisol secretion (76). Furthermore, the symptoms of IBS, such as abdominal pain, might activate the SNS and then reduce sleep efficiency (76, 77).

Our results revealed that the prevalence of IBS in university students was higher in Northwest China (19.10%, 95% CI: 7.02–42.46%), North China (17.66%, 95% CI: 7.37–36.64%) and Central China (15.93%, 95% CI: 8.28–28.47%), followed by East China (10.50%, 95% CI: 8.40–13.06%) and South China (3.18%, 95% CI: 1.28–7.68%). This might be due to the varied territory, climate, diet, traditional customs, the development of socioeconomic and employment prospects across China (48). In the coastal regions–East China and South China, the relatively more moderate climate might benefit people's health and the superior socioeconomic conditions effectively alleviate the psychological stress for university students there (78), leading to a lower prevalence of IBS.

Be consistent with the results of previous studies (79, 80), the prevalence estimation in the Rome III criteria group (12.00%) was higher than groups of Rome II (10.50%) and Rome IV criteria (3.66%). Diagnosis of IBS can be challenging. Compared to Rome III, Rome II criteria examine a 12-week period duration in the past 12 months, less than a continuous 6-month period, thus expanding the scope of diagnosis and being more stringent (81). Rome IV criteria requires that abdominal pain occurs on average at least 1 day per week while only 3 days a month were required in Rome III criteria. This might be the most important factor accounting for a reduction in the estimated prevalence of IBS from Rome III to Rome IV (82). Dai et al. (39) suggested that the choice between Rome II and Rome III criteria may affect the IBS diagnosis in females more than males. Another diagnosis of IBS–Manning criteria was regarded to be applied to the private housing group rather than the public housing group (83). Studies showed that Manning criteria was more appropriate for females (84), but less sensitive for males (85, 86). The applicable diagnostic criteria seem different according to the research population.

Furthermore, university students with drinking and smoking behaviors were more likely to report IBS. It was explained that alcohol could decrease muscle movements, which helps retain the food for further digestion in the small intestine and reduce the frequency and strength of muscle contractions in a segment of the rectum. This could further reduce the transit time and the compaction of the intestinal content. In addition, alcohol interferes with the activity of lactase, which breaks down the milk sugar lactose, resulting in lactose intolerance. Thus, diarrhea was frequently observed in alcoholics. Alcohol also inhibits some enzymes that participate in the metabolism of foreign organic substances in the gut. It directly disturbs the integrity of the mucosal epithelium and induces the release of noxious signaling molecules, which could damage the small blood vessels of capillaries in the intestinal mucosa and induce blood clotting. The resulting lesions allow large molecules, such as endotoxins and other bacterial toxins, to enter the bloodstream and the lymph. Therefore, alcohol-induced digestive disorders and mucosal damage in the gastrointestinal (GI) tract cause the change in the frequency and appearance of the stool, abdominal pain and bloating (87), which were the symptoms of IBS. For smokers, nicotine stimulates the sympathetic nerve to inhibit the movement of the disinfectant tract and the secretion of the gland, resulting in gastrointestinal emptying delay and absorption dysfunction. Another explanation could be that oxygen-free radicals from smoking could enhance lipid peroxidation, implicated with gastrointestinal dysfunction (88).

The results of this meta-analysis have implications for future research. The prevalence of IBS among university students in certain regions such as Northeast and Southwest China, needs further study for the overall estimation with greater precision. More population-based studies using Rome IV criteria are required to explore the appropriateness of this criteria on Chinese university students. Future longitudinal studies are needed to be adopted to establish the causal relationships between IBS and potential influencing factors, which are greatly warranted for intervention development.

The findings of this meta-analysis should be interpreted with caution due to several limitations. First, the 22 included studies involved only 14 of 34 provincial-level administrative regions in China, which limited the generalizability of the findings to all university students in China. Second, although subgroup analyses somewhat mitigated this limitation (89), heterogeneity was impossible to avoid in the meta-analysis of epidemiological studies. Third, the potential association between IBS and some factors, such as frequency of exercise, could not be examined in the subgroup analyses due to incomplete data or inconsistent reporting forms in most included studies. The miss of studies only exploring the associated factors without the prevalence of IBS might lead to the insufficiency of data on the analyses of associated factors of IBS. Therefore, our results of associated factors of IBS needed to be treated with caution. Finally, the causal inference between IBS and other factors was not allowed because of the cross-sectional design in all included studies.

This systematic review and meta-analysis showed that IBS was common (11.89%) in Chinese university students. The prevalence varied considerably in some instances, according to educational levels, geographic region, criteria used to define IBS. There are many associated factors of IBS, including female gender, majoring in medicine, anxiety, depression, drinking and smoking behavior. Further research should build on our findings and develop effective strategies for preventing and treating IBS in this population.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.

PX: conceptualization, methodology, software, resources, writing-original draft, writing-review and editing, supervision, project administration, and funding acquisition. TZ: conceptualization, methodology, and funding acquisition. WY: methodology, validation, formal analysis, investigation, data curation, and writing–original. XY: validation, formal analysis, investigation, data curation, writing-original draft, and visualization. XC: methodology, investigation, draft, and visualization. ZZ and HY: methodology, investigation, and visualization. XS: review and revision. All authors contributed to the article and approved the submitted version.

PX was supported by grants Moral Education Research Project for Teaching Science of Education Department of Guangdong Province (NO. 2019JKDY005) and National Natural Science Foundation of China (NO. 31970990). TZ was supported by grants Guangzhou Institute of Pediatrics/Guangzhou Women and Children's Medical Center funds (NO. GCP-2018-001) and Program of Guangzhou Municipal Science and Technology Bureau (NO. 201803010025). The funding body had no role in the study design, data collection, data analysis, data interpretation, the writing of the manuscript and the decision to submit the paper for publication. The research presented in this paper is that of the authors and does not reflect the official policy of Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, China. PX has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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