Abstract
Background
Although periodontal disease (PD) has been linked to an increased risk of several gastrointestinal diseases such as inflammatory bowel disease and celiac disease, research on the association between PD and irritable bowel syndrome (IBS) is still insufficiently explored, with conflicting results. We aimed to investigate the potential association between self‐reported oral symptoms and IBS based on the UK Biobank cohort.
Methods
Oral symptoms were assessed via questionnaire. Participants reporting at least one of gum pain, gum bleeding, or loose teeth were classified as being at high risk of PD. The primary outcome was incident IBS. Cox proportional hazards regression, incorporating multiple covariates, was applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) in examining the links between oral symptoms, high PD risk, and IBS incidence. Subgroup and sensitivity analyses were conducted.
Results
This longitudinal cohort study was conducted among 420,371 participants, 8642 incident cases of IBS (2.1%) were identified. Cox regression analyses showed that several oral symptoms, including mouth ulcers, gum pain, gum bleeding, toothache, and denture use, were significantly associated with an increased risk of IBS. No significant association was observed between loose teeth and IBS in any model. Compared with the low PD risk group, individuals at high risk of PD had an elevated likelihood of IBS onset (HR = 1.19, 95% CI: 1.13–1.25). Subgroup and sensitivity analyses strengthened the validity of these findings.
Conclusion
Oral symptoms (mouth ulcers, gum pain, gum bleeding, toothache, and denture use) and high risk of PD were both associated with an increased incidence of IBS. Incorporating oral health management into comprehensive strategies may contribute to the prevention of IBS.
Plain language summary
There is a close connection between oral health and gut health. This long‐term study of more than 420,000 UK adults found that individuals experiencing mouth ulcers, gum pain, gum bleeding, toothache, or denture use had a higher risk of developing irritable bowel syndrome (IBS) later in life. Additionally, participants classified as being at high risk for periodontal disease (PD; those with at least one symptom of gum pain, gum bleeding, or loose teeth) had about a 19% higher risk of developing IBS compared with the low PD risk group. Therefore, incorporating active management of oral problems into personal health practices could offer a new perspective for IBS prevention. Caring for oral health is not just about maintaining local wellness but is a crucial part of overall bodily health.
Keywords: cohort study, irritable bowel syndrome, periodontal disease, UK Biobank
1. INTRODUCTION
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by persistent abdominal discomfort, often occurring alongside alterations in bowel movements or behavior. The prevalence of IBS varies significantly across countries due to factors such as geographical location, diagnostic criteria, and demographic variables, including age, sex, and lifestyle. An extensive multinational research study reported the general prevalence of IBS as 3.8% (3.6%–4.0%) according to the Rome IV criteria. 1 IBS reduces the quality of life 2 and work productivity, 3 while also increasing healthcare utilization and the economic burden on society. 4 The pathophysiology of IBS entails multiple factors, involving dysbiosis of gut microbiota, impaired intestinal barrier function, visceral hypersensitivity, systemic hypoinflammation, and genetic predisposition. 1
A global study has shown that around 3.69 billion individuals worldwide are impacted by significant oral health issues, such as untreated dental caries, severe periodontitis, pulpal diseases, and other oral conditions. Among these, the most prevalent are untreated caries in permanent teeth and severe periodontitis. 5 Oral diseases impose a significant economic burden. In 2019, the global economic impact of oral diseases was estimated at USD 710 billion, with productivity losses due to periodontitis accounting for USD 82.10 billion. 6 Periodontal disease (PD), encompassing gingivitis and periodontitis, influences the supporting structures of the teeth, leading to progressive destruction of alveolar bone, periodontal attachment loss, and systemic inflammation. Porphyromonas gingivalis is widely recognized as the chief microbial agent implicated in both the initiation and advancement of chronic periodontitis. 7 Ecological dysbiosis of the dental plaque microbiota, excessive host immune responses, and genetic susceptibility contribute to the impairment of oral health. 7 , 8 Previous research has indicated that periodontitis is linked to numerous systemic health conditions, including rheumatoid arthritis, cardiovascular diseases, type 2 diabetes, obesity, chronic kidney disease, and so on. 9
Research on the association between oral health and IBS remains limited. A study demonstrated that the composition and abundance of oral microbiota in IBS patients differ from those in healthy participants. 10 Cross‐sectional studies have suggested that tooth loss and impaired masticatory function may increase the incidence of IBS. 11 , 12 The mechanisms linking oral health to gastrointestinal diseases have attracted widespread attention, highlighting the role of the oral–gut axis. Proposed mechanisms involve the ectopic colonization of oral pathogens, disruption of gut microbial homeostasis, activation of immune responses in the host, and damage to the intestinal mucosal barrier. 13 , 14 , 15 Earlier research has also pointed out that periodontitis may increase the risk of inflammatory bowel disease (IBD), 16 celiac disease, 17 chronic gastritis, and peptic ulcers. 18 However, a recent bidirectional Mendelian randomization study did not establish a causal link between periodontitis and IBS. 19 Given these contradictory findings, it is urgently necessary to obtain prospective evidence in a large sample population.
Based on the limited experimental and epidemiological evidence, we hypothesize that oral symptoms and PD may be associated with IBS. The current research aims to investigate the prospective association between self‐reported oral symptoms, high risk of PD and IBS using data from the large‐scale cohort of the UK Biobank, and to further explore whether this association is influenced by sociodemographic factors, lifestyle, and comorbidities.
2. MATERIALS AND METHODS
2.1. Study design and participants
The UK Biobank is a large‐scale biomedical database that recruited more than half a million participants aged 40–69 years between 2006 and 2010, who completed touch‐screen questionnaires and physical measurements, provided biospecimens, and electronically signed informed consent forms at 22 research assessment centers. The North West Multi‐centre Research Ethics Committee has approved the UK Biobank study. Prior to enrollment, all participants provided written informed consent. Participants free of IBS who had available records of mouth or dental problems at baseline were included. Participants diagnosed with IBD, cancer, or celiac disease at enrollment were excluded. Figure 1 presents the flowchart illustrating the recruitment procedure of participants.
FIGURE 1.
Flowchart of the participants. IBS, irritable bowel syndrome; IBD, inflammatory bowel disease.
2.2. Assessment of exposure
In the UK Biobank cohort, mouth or dental problems were assessed using a touchscreen questionnaire with the question, “Do you have any of the following questions? (You can select multiple answers).” Participants could select one or more responses, including mouth ulcers, painful gums, bleeding gums, loose teeth, toothache, dentures, or “None of the above.” Participants reporting one or more of these three symptoms (painful gums, bleeding gums, and loose teeth) were classified as at increased risk of PD. 20 , 21 A clinical diagnosis of periodontitis relies on periodontal examination parameters. 8 Therefore, we used self‐reported symptoms as a symptom‐based proxy of periodontal disease risk, supported by validation studies. 22 , 23 This approach was served as symptom‐based surrogate indicators of PD rather than as evidence of a clinically confirmed diagnosis. Those who did not report any of these symptoms were classified as low risk. Participants who selected “prefer not to answer” were excluded from the analysis.
2.3. Assessment of outcome
The outcome was new‐onset IBS, as defined by the International Classification of Diseases, 10th Revision (ICD‐10) code (K58). Case identification incorporated mapped historical clinical codes from multiple sources: self‐reported diagnoses, primary care records (Read codes), and hospital inpatient data (ICD‐9 and ICD‐10 codes), through UK Biobank's pre‐constructed “first occurrence” fields. The follow‐up period ended at the earliest of the following events: hospital record date, death, loss to follow‐up, or the censoring date (October 31, 2022), whichever occurred first.
2.4. Assessment of covariates
Covariate selection was guided by prior research findings and established epidemiological evidence, 1 , 8 , 21 , 24 included age (continuous variable), sex (male or female), ethnicity (White or non‐White), education (university or non‐university), physical activity (evaluated by the International Physical Activity Questionnaire [IPAQ] and classified into three levels: high, moderate, and low), Townsend Deprivation Index (divided into four quartiles to evaluate socioeconomic status), smoking status (never, current, or previous), alcohol drinking (never, current, or previous), body mass index (BMI, < 18.5 kg/m2, 18.5–24.9 kg/m2, 25.0–29.9 kg/m2, ≥ 30 kg/m2), comorbidities (history of type 2 diabetes mellitus, hypertension, anxiety, and depression). The specific UK Biobank data fields utilized in this analysis are listed (Table S1 in the online Journal of Periodontology).
2.5. Statistical analysis
Statistical analyses were conducted utilizing R software (version 4.4.0), with a significance level set at 0.05. For continuous variables with normal distributions, results were presented as mean values accompanied by standard deviations; for skewed distributions, medians and interquartile ranges were reported. Categorical data were summarized using counts and corresponding percentages. Missing data were treated as a separate category labeled “Unknown”.
Cox proportional hazards models were applied to estimate the association between oral symptoms, high risk of PD, and the risk of IBS, presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Four models were constructed: Model 1 was adjusted for basic demographics (baseline age, sex, and ethnicity); Model 2 was further adjusted for sociodemographic factors (education and Townsend Deprivation Index); Model 3 was additionally adjusted for lifestyle factors (smoking status, alcohol drinking, physical activity, and body weight status as measured by BMI); Model 4 was further adjusted for comorbidities (history of type 2 diabetes mellitus, hypertension, anxiety, and depression). Multicollinearity among variables was evaluated using variance inflation factors (VIFs), with a threshold of VIF > 5 indicating the presence of multicollinearity.
Subgroup and sensitivity analyses were performed with fully adjusted model. Subgroup analysis was performed to further verify whether the association between PD and IBS was influenced by grouping factors including sex, age, ethnicity, education, physical activity, Townsend Deprivation Index, BMI, smoking status, alcohol drinking status, and comorbidities. Likelihood ratio tests were applied to assess interactions.
To evaluate the robustness of the primary results, a series of sensitivity analyses were performed. First, we excluded participants diagnosed with IBS within 1 or 2 years after baseline to mitigate the impact of reverse causality. Second, a new dataset was generated by matching all covariates in a 1:1 ratio to further explore the association. Third, competing risk models were developed, considering death and loss to follow‐up as alternative outcomes, since these individuals might have later experienced IBS. Fourth, to reduce potential confounding bias, inverse probability weighting was employed.
3. RESULTS
3.1. Baseline characteristics
The analysis included 420,371 participants. The mean age at recruitment was 56.26 ± 8.12 years, and 47.84% of the participants were male. A total of 345,043 (82.08%) participants were classified as low risk for PD, while 75,328 (17.92%) were classified as high risk. Individuals classified as high risk of PD were more likely to be female, non‐White, current or former smokers, less physically active, obese, and to have comorbidities (Table 1). During a median follow‐up of 13.7 years, 8642 (2.1%) participants were diagnosed with IBS after the baseline assessment. For those identified as high‐risk for PD, IBS developed at a rate of roughly 1.94 cases per 1000 person‐years (Table 2). Baseline characteristics, grouped by IBS diagnosis status, are presented in Table S2 in the online Journal of Periodontology. Compared to those without IBS, individuals with IBS were more often female and former alcohol consumers. They also tended to have lower socioeconomic status and a greater burden of comorbidities (Table S2).
TABLE 1.
Baseline characteristics of participants grouped by high/low risk of periodontal disease.
| Exposure | |||
|---|---|---|---|
| Characteristic | Overall | Low risk of periodontal disease | High risk of periodontal disease |
| n (%) | 420,371 | 345,043 (82.08) | 75,328 (17.92) |
| Age, years (mean ± SD) | 56.26 ± 8.12 | 56.54 ± 8.12 | 54.97 ± 7.96 |
| Sex, n (%) | |||
| Female | 219,270 (52.16) | 176,210 (51.07) | 43,060 (57.16) |
| Male | 201,101 (47.84) | 168,833 (48.93) | 32,268 (42.84) |
| Ethnicity, n (%) | |||
| Non‐white | 24,169 (5.75) | 17,441 (5.05) | 6728 (8.93) |
| White | 394,754 (93.91) | 326,443 (94.61) | 68,311 (90.68) |
| Unknown | 1448 (0.34) | 1159 (0.34) | 289 (0.38) |
| Education, n (%) | |||
| Non‐university | 277,875 (66.10) | 227,378 (65.90) | 50,497 (67.04) |
| University | 138,112 (32.85) | 114,098 (33.07) | 24,014 (31.88) |
| Unknown | 4384 (1.04) | 3567 (1.03) | 817 (1.08) |
| IPAQ, n (%) | |||
| Low | 60,094 (14.30) | 47,946 (13.90) | 12,148 (16.13) |
| Moderate | 132,735 (31.58) | 109,116 (31.62) | 23,619 (31.35) |
| High | 134,476 (31.99) | 112,383 (32.57) | 22,093 (29.33) |
| Unknown | 93,066 (22.14) | 75,598 (21.91) | 17,468 (23.19) |
| Townsend Deprivation Index, n (%) | |||
| Q1 (≤−3.64) | 104,972 (24.97) | 88,792 (25.73) | 16,180 (21.48) |
| Q2 (−3.64 to −2.13) | 105,102 (25.00) | 87,969 (25.50) | 17,133 (22.74) |
| Q3 (−2.13 to 0.55) | 104,972 (24.97) | 86,002 (24.93) | 18,970 (25.18) |
| Q4 (>0.55) | 104,794 (24.93) | 81,871 (23.73) | 22,923 (30.43) |
| Unknown | 531 (0.13) | 409 (0.12) | 122 (0.16) |
| Smoking status, n (%) | |||
| Never | 231,089 (54.97) | 192,015 (55.65) | 39,074 (51.87) |
| Previous | 143,078 (34.04) | 115,570 (33.49) | 27,508 (36.52) |
| Current | 44,672 (10.63) | 36,172 (10.48) | 8500 (11.28) |
| Unknown | 1532 (0.36) | 1286 (0.37) | 246 (0.33) |
| Alcohol drinking, n (%) | |||
| Never | 18,552 (4.41) | 14,843 (4.30) | 3709 (4.92) |
| Previous | 14,506 (3.45) | 11,560 (3.35) | 2946 (3.91) |
| Current | 386,848 (92.03) | 318,290 (92.25) | 68,558 (91.01) |
| Unknown | 465 (0.11) | 350 (0.10) | 115 (0.15) |
| BMI, n (%) | |||
| <18.5 kg/m2 | 134,323 (31.95) | 111,890 (32.43) | 22,433 (29.78) |
| 18.5–24.9 kg/m2 | 2005 (0.48) | 1674 (0.49) | 331 (0.44) |
| 25.0–29.9 kg/m2 | 178,877 (42.55) | 147,962 (42.88) | 30,915 (41.04) |
| ≥30 kg/m2 | 102,692 (24.43) | 81,570 (23.64) | 21,122 (28.04) |
| Unknown | 2474 (0.59) | 1947 (0.56) | 527 (0.70) |
| Diabetes, n (%) | |||
| No | 409,426 (97.40) | 336,413 (97.50) | 73,013 (96.93) |
| Yes | 10,945 (2.60) | 8630 (2.50) | 2315 (3.07) |
| Anxiety, n (%) | |||
| No | 406,085 (96.60) | 333,883 (96.77) | 72,202 (95.85) |
| Yes | 14,286 (3.40) | 11,160 (3.23) | 3126 (4.15) |
| Depression, n (%) | |||
| No | 387,850 (92.26) | 320,201 (92.80) | 67,649 (89.81) |
| Yes | 32,521 (7.74) | 24,842 (7.20) | 7679 (10.19) |
| Hypertension, n (%) | |||
| No | 309,114 (73.53) | 254,546 (73.77) | 54,568 (72.44) |
| Yes | 111,257 (26.47) | 90,497 (26.23) | 20,760 (27.56) |
Abbreviations: BMI, body mass index; IPAQ, International Physical Activity Questionnaire.
TABLE 2.
Association between oral symptoms, periodontal disease, and irritable bowel syndrome.
| Oral health | Incident rate per 1000 person‐years | Model 1 | Model 2 | Model 3 | Model 4 |
|---|---|---|---|---|---|
| HR (95%CI) | HR (95%CI) | HR (95%CI) | HR (95%CI) | ||
| Mouth ulcer | 2.28 | 1.49 (1.40–1.58) | 1.49 (1.41–1.59) | 1.49 (1.40–1.58) | 1.44 (1.36–1.53) |
| Painful gums | 2.81 | 1.76 (1.60–1.93) | 1.72 (1.56–1.89) | 1.66 (1.51–1.83) | 1.56 (1.42–1.72) |
| Bleeding gums | 1.96 | 1.24 (1.17–1.31) | 1.23 (1.16–1.30) | 1.22 (1.15–1.29) | 1.19 (1.12–1.26) |
| Loose teeth | 1.56 | 0.96 (0.93–1.15) | 0.99 (0.90–1.11) | 0.96 (0.86–1.07) | 0.93 (0.84–1.03) |
| Toothache | 2.27 | 1.55 (1.42–1.69) | 1.54 (1.41–1.67) | 1.50 (1.38–1.64) | 1.45 (1.33–1.58) |
| Dentures | 1.83 | 1.28 (1.21–1.35) | 1.21 (1.14–1.28) | 1.17 (1.10–1.24) | 1.14 (1.08–1.21) |
| High risk of periodontal disease | 1.94 | 1.26 (1.20–1.33) | 1.25 (1.18–1.31) | 1.23 (1.16–1.29) | 1.19 (1.13–1.25) |
Model 1 was adjusted for basic demographics (baseline age, sex, and ethnicity); Model 2 was further adjusted for sociodemographic factors (education and Townsend Deprivation Index); Model 3 was additionally adjusted for lifestyle factors (smoking status, alcohol drinking, physical activity, and BMI); Model 4 was further adjusted for comorbidities (history of type 2 diabetes mellitus, hypertension, anxiety, and depression). Incidence rate per 1000 person‐years = (Number of cases with a specific oral health problem / Total person‐years with that specific oral health problem) × 1000.
Abbreviations: CI, confidence interval; HR, hazard ratio.
3.2. Association between oral health and IBS
Among the oral symptoms evaluated, individuals reporting painful gums exhibited the highest incidence rate of IBS at 2.81 per 1000 person‐years, followed by those with mouth ulcers (2.28), toothache (2.27), bleeding gums (1.96), and loose teeth (1.56).
In the fully adjusted model, painful gums demonstrated a substantially elevated risk of IBS, with a 56% increase (HR = 1.56, 95% CI: 1.42–1.72). Similarly, both mouth ulcers and toothache showed moderate risks, at 44% (HR = 1.44, 95% CI: 1.36–1.53) and 45% (HR = 1.45, 95% CI: 1.33–1.58) respectively. Bleeding gums and dentures were associated with a 19% (HR = 1.19, 95% CI: 1.12–1.26) and a 14% (HR = 1.14, 95% CI: 1.08–1.21) increased risk of IBS, respectively. A fully adjusted HR of 1.19 (95% CI: 1.13–1.25) for high periodontal disease risk indicates that participants at high risk of PD had a 19% higher risk of developing IBS during the follow‐up period compared to those with low risk, after adjusting for all covariates. No association was found between loose teeth and IBS (HR = 0.93, 95% CI: 0.84–1.03). The results of other models are presented in Table 2.
3.3. Subgroup analyses
After adjusting for all potential confounders, subgroup analyses showed that the elevated risk of IBS linked to PD persisted across diverse population groups, except among current smokers, never drinkers, and individuals previously diagnosed with anxiety. No significant interaction was observed between any covariates and PD in relation to the risk of IBS (Figure 2).
FIGURE 2.
Subgroup analysis of the association between high risk of periodontal disease and irritable bowel syndrome. BMI, body mass index’ CI, confidence interval; IPAQ, International Physical Activity Questionnaire; HR, hazard ratio.
3.4. Sensitivity analyses
We conducted the following sensitivity analyses (Table 3). First, to minimize the risk of reverse causality, participants diagnosed with IBS within 1 or 2 years following baseline were excluded. This approach revealed that a high PD risk was associated with a 21% (HR = 1.21, 95% CI: 1.14–1.28) and a 19% (HR = 1.19, 95% CI: 1.13–1.25) increased IBS risk in Model 4, respectively. Second, we performed propensity score matching based on all covariates used in Model 4 to create a balanced sample of exposed and unexposed individuals. In the matched cohort (n = 150,656), the association remained robust with an adjusted HR of 1.19 (95% CI: 1.12–1.27), again using Model 4 to adjust for residual confounding. Third, a competing risk model accounting for death as a competing event yielded an HR of 1.18 (95% CI: 1.13–1.25), indicating that the observed risk elevation was not substantially biased by differential survival. Lastly, inverse probability weighting was applied to mitigate selection bias. The adjusted risk ratio was 1.18 (95% CI: 1.12–1.25).
TABLE 3.
Results of sensitivity analyses.
| Sensitivity analysis | No. of IBS | No. of participants | Adjusted HR (95%CI) |
|---|---|---|---|
| Excluded participants with IBS records within the first 1 year from baseline | 7938 | 419,667 | 1.19 (1.13–1.25) |
| Excluded participants with IBS records within the first 2 years from baseline | 7246 | 418,975 | 1.21 (1.14–1.28) |
| Applied propensity score matching | 3539 | 150,656 | 1.19 (1.12–1.27) |
| Applied competing risk mode | 8642 | 420,371 | 1.18 (1.13–1.25) |
| Applied inverse probability weighting method | 8642 | 420,371 | 1.18 (1.12–1.25) |
Note: The analyses were performed using Cox regression in Model 4.
Abbreviations: CI, confidence interval; HR, hazard ratio; IBS, irritable bowel syndrome.
4. DISCUSSION
In this prospective cohort study, we examined the association between a high risk of PD and IBS, accounting for potential confounding factors, including sociodemographic characteristics, lifestyle, and comorbid conditions. Given the very large sample size of this cohort, it is expected that even modest differences in risk may reach statistical significance. Therefore, we place greater emphasis on the magnitude and consistency of the effect estimates. Our analysis found that in the fully adjusted model, the associations between oral health indicators and IBS were generally modest, with hazard ratios ranging from 1.14 to 1.56 for oral ulcers, gum pain, gum bleeding, toothache, and PD. This indicates a consistent and small‐to‐moderate increase in HRs. Findings from subgroup and sensitivity analyses reinforced the consistency of this association.
There are a limited number of studies investigating the relationship between PD and IBS, with inconsistent conclusions. Tooth loss is often the final consequence of PD. 8 A cross‐sectional study conducted among 4669 Iranian adults found that losing one to two or three to five teeth was linked to a higher likelihood of developing IBS. 11 Another cross‐sectional study among Iranian adolescent girls reported that tooth loss was linked to a greater occurrence of IBS. 12 However, a Mendelian randomization study found no evidence for a bidirectional link between periodontitis and IBS. 19 The observed inconsistencies may be attributed to limited sample sizes, methodological heterogeneity, and the absence of cohort studies to establish causality.
In subgroup analyses of current smokers, never drinkers, and participants with a prior diagnosis of anxiety, no statistically association was observed between PD and the risk of IBS. No evidence of interaction was observed between PD and any of the examined covariates regarding IBS risk, indicating the consistency of the findings across these population subgroups.
In light of the commonality of PD and the rising healthcare burden associated with IBS, our findings may have important clinical implications. Patients presenting with oral symptoms, particularly oral ulcers, gingival pain, gingival bleeding, or dental pain, or those diagnosed with PD, should be assessed for the likelihood of having IBS if they also experience abdominal pain or changes in bowel habits. Moreover, maintaining good oral habits may help prevent IBS.
Multiple plausible mechanisms may underlie the observed link between PD and the development of IBS. First, periodontitis‐associated microbes, such as P. gingivalis, T. forsythia, and T. denticola, may metastasize to and proliferate in the intestine via swallowed saliva. This translocation can lead to gut dysbiosis and mucosal damage through bacterial toxins and metabolites, thereby facilitating the development of IBS. 13 , 25 The overgrowth of these pathogenic bacteria may directly aggravate chronic intestinal inflammation by elevating mucosal levels of inflammatory cytokines, including interleukin (IL)‐1, IL‐6, IL‐17, and tumor necrosis factor (TNF)‐α. 26 Hematogenous dissemination of bacteria and their metabolites may contribute to the development and progression of systemic diseases. 27 In a mouse model of periodontitis induced by oral administration of P. gingivalis, expression levels of tight junction–related genes were diminished in the intestinal tissue, suggesting a disruption of the gut barrier's integrity. 28 , 29 Second, oxidative stress may represent another potential mechanism linking PD to systemic diseases. In patients with chronic periodontitis, salivary total antioxidant capacity tends to decrease, whereas concentrations of malondialdehyde, nitric oxide, and overall oxidative status are markedly elevated. 30 , 31 Clinical evidence has further indicated that individuals with IBS have elevated serum malondialdehyde and nitric oxide levels, along with decreased activity of antioxidant enzymes pattern that mirrors observations in periodontitis. 32 Third, patients with PD often experience gingival swelling and pain, along with tooth mobility. Consequently, their preference shifts from natural foods (e.g., leafy vegetables and fruits) to ultra‐processed foods (UPFs) (e.g., biscuits and chips) like biscuits and chips. 33 A significant dose–response relationship has been observed between high intake of UPFs and an increased risk of IBS. 34 Furthermore, the discomfort caused by oral symptoms and the financial burden of treatment may both contribute to a higher likelihood of psychological stress, such as anxiety and depression. 35 Psychological factors may affect the likelihood of IBS and the quality of life of patients. 36
As far as we are aware, this is the first longitudinal study to explore the relationship between PD and IBS using UK Biobank data. By adjusting for multiple covariates, our study strengthens the validity of the observed associations. The consistency of these associations, as evidenced by subgroup and sensitivity analyses, supports a link between PD and incident IBS. The current study enhances our comprehension of the interplay between oral health and gastrointestinal disorders.
Several limitations should be acknowledged in this study. First, IBS was not defined using the Rome IV criteria, and mild or unreported cases may have led to under‐ascertainment of incident IBS. Second, the classification of PD risk was based solely on the presence or absence of self‐reported oral symptoms without confirmation through professional dental examination. Although these symptom‐based measures have been used as surrogate indicators in prior studies, the available validation evidence remains limited, and further validation against standardized clinical periodontal assessments is warranted. Because this symptom‐based surrogate may reduce diagnostic accuracy and introduce misclassification of PD risk, the findings should be interpreted with appropriate caution. Additionally, PD status was assessed only at baseline and was not monitored over time, possibly missing incident cases during follow‐up and thereby potentially underestimating the association between PD and IBS. Third, data regarding the severity of PD were unavailable, making it impossible to determine whether more severe PD is associated with a higher risk of IBS. Fourth, although adjustments were made for multiple covariates, residual confounding cannot be completely ruled out. Fifth, observed HRs were small‐to‐moderate. Nevertheless, considering the high prevalence of both periodontal disease and IBS, even these modest relative increases in risk may translate into a substantial disease burden at the population level, which carries public health implications. Finally, given that the UK Biobank cohort predominantly consists of White participants, the extent to which these findings apply to more diverse racial or ethnic groups remains uncertain.
5. CONCLUSION
To summarize, the present study demonstrated a robust association between several self‐reported oral symptoms, high risk of PD, and an elevated risk of IBS. The underlying mechanisms of this association remain incompletely understood. Additional studies are needed to identify high‐risk populations and to formulate targeted strategies for improving oral health. These efforts may offer new perspectives on IBS prevention.
AUTHOR CONTRIBUTIONS
Zhuoya Sun conceived and designed the study, collected data, performed statistical analysis, interpreted results, and drafted the manuscript. Laifu Li contributed to result interpretation and manuscript revision. Yan Zhuang and Xiaoting Hu assisted with data analysis and interpretation. Jiamiao Chen and Shiwei Lu reviewed the manuscript. Fei Dai contributed to study design and manuscript review. All authors approved the final version and are responsible for the work.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
FUNDING INFORMATION
This study received no financial support from any funding agency.
ETHICS STATEMENT
Ethical approval for the UK Biobank study was granted by the North West Multi‐centre Research Ethics Committee. All participants provided written informed consent prior to their enrollment in the study.
CONSENT FOR PUBLICATION
This research has been conducted using the UK Biobank resource under application number 99732. All participants provided informed consent at the time of data collection.
Supporting information
Supporting Information
ACKNOWLEDGMENTS
This research has been conducted using the UK Biobank resource under application number 99732. We express our gratitude to the UK Biobank participants and staff for their valuable contributions and commitment to this study.
Sun Z, Li L, Zhuang Y, et al. Association between self‐reported oral symptoms and irritable bowel syndrome: A prospective cohort study based on UK Biobank. J Periodontol. 2026;97:1819–1829. 10.1002/jper.70125
Zhuoya Sun and Laifu Li are co‐first authors who made equal contributions to this study.
DATA AVAILABILITY STATEMENT
All primary data used in this study are available through the UK Biobank (https://www.ukbiobank.ac.uk), subject to standard application procedures, under application number 99732.
REFERENCES
- 1. Ford AC, Sperber AD, Corsetti M, Camilleri M. Irritable bowel syndrome. Lancet. 2020;396(10263):1675‐1688. doi: 10.1016/S0140-6736(20)31548-8 [DOI] [PubMed] [Google Scholar]
- 2. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of rome foundation global study. Gastroenterology. 2021;160(1):99‐114.e113. doi: 10.1053/j.gastro.2020.04.014 [DOI] [PubMed] [Google Scholar]
- 3. Frändemark Å, Törnblom H, Jakobsson S, Simrén M. Work productivity and activity impairment in Irritable Bowel Syndrome (IBS): a multifaceted problem. AM J Gastroenterol. 2018;113(10):1540‐1549. https://journals.lww.com/ajg/fulltext/2018/10000/work_productivity_and_activity_impairment_in.27.aspx [DOI] [PubMed] [Google Scholar]
- 4. Tornkvist NT, Aziz I, Whitehead WE, et al. Health care utilization of individuals with Rome IV irritable bowel syndrome in the general population. United European Gastroenterol J. 2021;9(10):1178‐1188. doi: 10.1002/ueg2.12153 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Collaborators GOD. Trends in the global, regional, and national burden of oral conditions from 1990 to 2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2025;405(10482):897‐910. doi: 10.1016/s0140-6736(24)02811-3 [DOI] [PubMed] [Google Scholar]
- 6. Jevdjevic M, Listl S. Global, regional, and country‐level economic impacts of oral conditions in 2019. J Dent Res. 2025;104(1):17‐21. doi: 10.1177/00220345241281698 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Nakayama M, Ohara N. Molecular mechanisms of Porphyromonas gingivalis‐host cell interaction on periodontal diseases. Jpn Dent Sci Rev. 2017;53(4):134‐140. doi: 10.1016/j.jdsr.2017.06.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3:17038. doi: 10.1038/nrdp.2017.38 [DOI] [PubMed] [Google Scholar]
- 9. Hajishengallis G. Interconnection of periodontal disease and comorbidities: evidence, mechanisms, and implications. Periodontol 2000. 2022;89(1):9‐18. doi: 10.1111/prd.12430 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Tang B, Hu Y, Chen J, Su C, Zhang Q, Huang C. Oral and fecal microbiota in patients with diarrheal irritable bowel syndrome. Heliyon. 2023;9(1):e13114. doi: 10.1016/j.heliyon.2023.e13114 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Esmaillzadeh A, Keshteli AH, Saneei T, Saneei P, Savabi O, Adibi P. Is tooth loss associated with irritable bowel syndrome? J Oral Rehabil. 2015;42(7):503‐511. doi: 10.1111/joor.12277 [DOI] [PubMed] [Google Scholar]
- 12. Khayyatzadeh SS, Kazemi‐Bajestani SMR, Mirmousavi SJ et al. Dietary behaviors in relation to prevalence of irritable bowel syndrome in adolescent girls. J Gastroenterol Hepatol. 2018;33(2):404‐410. doi: 10.1111/jgh.13908 [DOI] [PubMed] [Google Scholar]
- 13. Zhou T, Xu W, Wang Q et al. The effect of the “Oral‐Gut” axis on periodontitis in inflammatory bowel disease: a review of microbe and immune mechanism associations. Front Cell Infect Microbiol. 2023;13:1132420. doi: 10.3389/fcimb.2023.1132420 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Tanwar H, Gnanasekaran JM, Allison D et al. unravelling the oral‐gut axis: interconnection between periodontitis and inflammatory bowel disease, current challenges, and future perspective. J Crohns Colitis. 2024;18(8):1319‐1341. doi: 10.1093/ecco-jcc/jjae028 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Kitamoto S, Nagao‐Kitamoto H, Jiao Y et al. The intermucosal connection between the mouth and gut in commensal pathobiont‐driven colitis. Cell. 2020;182(2):447‐462.e14. doi: 10.1016/j.cell.2020.05.048 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Park YM, Park JD, Leem GH, Song TM. Periodontitis and the incidence of inflammatory bowel diseases: a nationwide population‐based cohort study. Am J Gastroenterol. 2025;120(10):2361‐2372. doi: 10.14309/ajg.0000000000003326 [DOI] [PubMed] [Google Scholar]
- 17. Madi M, Abdelsalam M, Elakel A et al. Salivary interleukin‐17A and interleukin‐18 levels in patients with celiac disease and periodontitis. PeerJ. 2024;12:e17374. doi: 10.7717/peerj.17374 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Byun SH, Min C, Hong SJ, Choi HG, Koh DH. Analysis of the relation between periodontitis and chronic gastritis/peptic ulcer: a cross‐sectional study using KoGES HEXA data. Int J Environ Res Public Health. 2020;17(12):4387. doi: 10.3390/ijerph17124387 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Wang Y, Zhu J, Tang Y, Huang C. Association of periodontitis with gastrointestinal tract disorders: a bidirectional Mendelian randomization study. J Periodontol. 2024;95(10):1002‐1010. doi: 10.1002/jper.23-0560 [DOI] [PubMed] [Google Scholar]
- 20. Watson S, Woodside JV, Winning L, Wright DM, Srinivasan M, McKenna G. Associations between self‐reported periodontal disease and nutrient intakes and nutrient‐based dietary patterns in the UK Biobank. J Clin Periodontol. 2022;49(5):428‐438. doi: 10.1111/jcpe.13604 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Wang D, Dai L, Cui Z et al. Association between periodontal diseases and chronic obstructive pulmonary disease: evidence from sequential cross‐sectional and prospective cohort studies based on UK Biobank. J Clin Periodontol. 2024;51(1):97‐107. doi: 10.1111/jcpe.13890 [DOI] [PubMed] [Google Scholar]
- 22. Eke PI, Dye BA, Wei L et al. Self‐reported measures for surveillance of periodontitis. J Dent Res. 2013;92(11):1041‐1047. doi: 10.1177/0022034513505621 [DOI] [PubMed] [Google Scholar]
- 23. Abbood HM, Hinz J, Cherukara G, Macfarlane TV. Validity of self‐reported periodontal disease: a systematic review and meta‐analysis. J Periodontol. 2016;87(12):1474‐1483. doi: 10.1902/jop.2016.160196 [DOI] [PubMed] [Google Scholar]
- 24. Wu S, Yuan C, Yang Z et al. Non‐alcoholic fatty liver is associated with increased risk of irritable bowel syndrome: a prospective cohort study. BMC Med. 2022;20(1):262. doi: 10.1186/s12916-022-02460-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Xi M, Ruan Q, Zhong S et al. Periodontal bacteria influence systemic diseases through the gut microbiota. Front Cell Infect Microbiol. 2024;14:1478362. doi: 10.3389/fcimb.2024.1478362 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Kitamoto S, Kamada N. Periodontal connection with intestinal inflammation: microbiological and immunological mechanisms. Periodontol 2000. 2022;89(1):142‐153. doi: 10.1111/prd.12424 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Hajishengallis G, Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat Rev Immunol. 2021;21(7):426‐440. doi: 10.1038/s41577-020-00488-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Liu Y, Huang W, Wang J et al. Multifaceted impacts of periodontal pathogens in disorders of the intestinal barrier. Front Immunol. 2021;12:693479. doi: 10.3389/fimmu.2021.693479 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Feng YK, Wu QL, Peng YW et al. Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice. J Neuroinflammation. 2020;17(1):347. doi: 10.1186/s12974-020-02027-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Chen M, Cai W, Zhao S et al. Oxidative stress‐related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: a systematic review and meta‐analysis. J Clin Periodontol. 2019;46(6):608‐622. doi: 10.1111/jcpe.13112 [DOI] [PubMed] [Google Scholar]
- 31. Sczepanik FSC, Grossi ML, Casati M et al. Periodontitis is an inflammatory disease of oxidative stress: we should treat it that way. Periodontol 2000. 2020;84(1):45‐68. doi: 10.1111/prd.12342 [DOI] [PubMed] [Google Scholar]
- 32. Roudsari NM, Lashgari NA, Zandi N et al. PPARγ: a turning point for irritable bowel syndrome treatment. Life Sci. 2020;257:118103. doi: 10.1016/j.lfs.2020.118103 [DOI] [PubMed] [Google Scholar]
- 33. Canaan J, Canaan MM, Costa PD et al. Food preferences and periodontal status of adults assisted by a public health care system. PLoS One. 2023;18(10):e0291878. doi: 10.1371/journal.pone.0291878 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Wu S, Yang Z, Liu S, Zhang Q, Zhang S, Zhu S. Ultra‐processed food consumption and long‐term risk of irritable bowel syndrome: a large‐scale prospective cohort study. Clin Gastroenterol Hepatol. 2024;22(7):1497‐1507.e5. doi: 10.1016/j.cgh.2024.01.040 [DOI] [PubMed] [Google Scholar]
- 35. Wang J, Wang Y, Li H, Wang W, Zhang D. Associations between oral health and depression and anxiety: a cross‐sectional and prospective cohort study from the UK Biobank. J Clin Periodontol. 2024;51(11):1466‐1477. doi: 10.1111/jcpe.14039 [DOI] [PubMed] [Google Scholar]
- 36. Qin HY, Cheng CW, Tang XD, Bian ZX. Impact of psychological stress on irritable bowel syndrome. World J Gastroenterol. 2014;20(39):14126‐14131. doi: 10.3748/wjg.v20.i39.14126 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supporting Information
Data Availability Statement
All primary data used in this study are available through the UK Biobank (https://www.ukbiobank.ac.uk), subject to standard application procedures, under application number 99732.