Association Between Toothbrushing Habits and Mucosal Healing in Japanese Patients with Ulcerative Colitis

Abstract

Objective

Evidence regarding the association between oral environment and the inflammatory bowel disease (IBD), including ulcerative colitis (UC), exists. However, evidence regarding the association between oral health parameters and disease activity of UC is limited. This study aimed to evaluate the association between remaining tooth number and toothbrushing frequency and mucosal healing (MH) in Japanese UC patients.

Method

The study included 275 patients with UC. Information on lifestyle and oral health parameters was collected via self-administered questionnaires. The definition of MH was based on the Mayo endoscopic subscore (MES) of 0.

Results

The prevalence of MH in this cohort was 24.7%. The distribution of remaining teeth was as follows: 13.1% had 20 or fewer teeth, 32.7% had 20–27 teeth, and 54.2% had 28 teeth. Toothbrushing frequency was 23.6% brushed once or less per day, 46.9% brushed twice per day, and 29.5% brushed three or more times per day. No significant difference was observed between remaining teeth and MH. However, toothbrushing frequency is independently positively associated with MH (adjusted odds ratio: 2.87 [95% CI: 1.19–7.29]; p value for trend = 0.021).

Conclusion

Toothbrushing frequency but not the remaining tooth number might be independently and positively associated with MH in Japanese patients with UC.

Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by recurrent inflammation of the colonic mucosa, leading to mucosal ulceration, diarrhea, and rectal bleeding [1].

In recent years, evidence regarding the association between extraintestinal factors, including the oral environment and IBD, has increased [2–4]. The oral cavity and gut share a complex immunological and microbial interface, and dysbiosis in the oral microbiome has been implicated in intestinal inflammation through the oral–gut axis [2, 5, 6].

Periodontal disease and dental caries are both closely associated with tooth loss and are linked to systemic inflammation and mortality. Several epidemiological studies show the association between periodontitis and UC and Crohn’s disease (CD) [7–9]. A similarly close association between dental caries and IBD was reported in several studies [10–12]. Moreover, associations of periodontal disease and subsequent tooth loss with IBD activity have been reported [13]. In a previous study of patients with UC, the number of tooth losses is associated with quality of life [14].

Toothbrushing frequency is inversely associated with periodontitis and dental caries. Toothbrushing plays a key role in reducing oral bacterial load and inflammation, which may in turn modulate gut microbiota composition and systemic inflammatory responses [3, 6, 15]. Some previous studies investigated the association between frequency of toothbrushing and incidence of IBD [15, 16]. We hypothesized that the number of remaining teeth and frequency of toothbrushing may be associated with disease activity in patients with UC. Mucosal healing (MH) has become an important therapeutic goal in UC, as it is associated with sustained clinical remission and improved long-term outcomes [17].

However, evidence regarding the association between oral hygiene behavior and intestinal mucosal outcomes in ulcerative colitis remains limited. In particular, it is unclear whether daily oral health practices are related to objective endoscopic outcomes. Therefore, the present study aimed to investigate the relationship between oral health parameters including the number of remaining teeth and toothbrushing frequency, and MH in patients with UC.

Materials and Methods

Ethics Approval and Consent to Participate

This cross-sectional analysis was conducted using baseline data derived from an ongoing prospective cohort. The study protocol was reviewed and approved by the Clinical Trial Review Committee of the Ehime University Graduate School of Medicine (approval number: 1505011). All procedures adhered to the ethical standards outlined in the Declaration of Helsinki (1964) and its later amendments. Written informed consent was obtained from all participants by trained research personnel. The study was prospectively registered in the University Hospital Medical Information Network (UMIN000051334).

Study Population

This study included 275 patients with UC who received clinical management, either as inpatients or outpatients, at the Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, and its affiliated institutions in Ehime Prefecture, Japan, between 2015 and 2019. The diagnosis of UC was established according to characteristic endoscopic features and confirmed by clinical, radiologic, and histopathological assessments. All participants gave informed consent and were capable of completing a self-administered questionnaire.

Measurement Items

Information on lifestyle habits and socioeconomic factors, including smoking status, alcohol consumption, toothbrushing frequency, remaining teeth, and household income, was collected via self-administered questionnaires. Clinical details such as use of UC medications, disease extent, and duration of disease were extracted from medical records. Participants reporting smoking at the time of the survey were classified as current smokers, regardless of the number of cigarettes smoked. Similarly, individuals reporting regular drinking habits were considered current drinkers, regardless of frequency or amount consumed.

Definition of Clinical Remission (CR) and Mucosal Healing (MH)

Endoscopic activity of UC was assessed by endoscopists with colonoscopy. Clinical remission (CR) was defined as the absence of rectal bleeding and abnormal frequency of bowel movements (less than 3 times per day) [18]. Clinical symptoms were assessed by board-certified gastroenterologists. In this study, a Mayo Endoscopic Score (MES) of 0 was defined as a disease-free state (MH) [19]. One endoscopist assessed both MES and MH while blinded to oral health parameters.

Number of Remaining Teeth and Frequency of Tooth Brushing

The number of remaining teeth was assessed using a self-administered questionnaire. Participants responded to the following question: ‘Currently, excluding wisdom teeth, how many of your own natural teeth do you have in total, upper and lower combined? (Permanent teeth excluding wisdom teeth total 28. Please exclude dental implants).’ Respondents reported the number in free-text format.

A self-administered questionnaire was used to assess toothbrushing habits. Participants were first asked whether they brushed their teeth daily (yes/no). Those who answered “yes” were subsequently asked to report the number of times they brushed their teeth per day, and they provided an approximate daily frequency in a free-response format. The cutoff of fewer than 20 teeth was selected because this threshold has been used in previous epidemiological studies as a clinically meaningful indicator of tooth loss associated with adverse health outcomes [13, 20]. The 28 teeth group was regarded as complete dentition, as the total number of permanent teeth excluding wisdom teeth is 28.

Statistical Analysis

Remaining teeth were categorized into three groups: (1) fewer than 20 teeth, (2) 21 to 27 teeth, and (3) 28 teeth. Tooth brushing frequency was also categorized into three groups: (1) once per day or less, (2) twice per day, and (3) three or more times per day. Odds ratios (OR) and adjusted ORs were estimated using logistic regression analysis, along with 95% confidence intervals (CI). Sex was considered as a biological variable in the study design and statistical analyses. Both male and female patients were included without sex-based exclusion criteria. Multivariable models were adjusted for sex to account for potential biological differences. The multivariate model adjusted for age, sex, prednisolone use, alcohol consumption, smoking, BMI, disease duration, and disease extent. Analyses were performed using SAS 9.4 (SAS Institute, Cary, NC, USA), and a two-sided p value < 0.05 was considered statistically significant.

Results

A total of 275 patients with UC were included in the analysis (Table 1). The median age was 50.65 years, and 58.2% were male. The prevalence of MH (MES 0) and CR were 24.7% and 59.3%, respectively. The average number of remaining teeth was 24.6. The distribution was as follows: 13.1% had 20 or fewer remaining teeth, 32.7% had 20 to 27 remaining teeth, and 54.2% had 28 remaining teeth. The frequency of toothbrushing was 23.6% (n = 65) for ≤ 1 time/day, 46.9% (n = 129) for 2 times/day, and 29.5% (n = 81) for ≥ 3 times/day, respectively.

Table 1.

Clinical characteristics of 275 study participants

Variables	Mean ± SD or n (%)
Age (years)	50.65 ± 15.9
Male (%)	160 (58.2)
Disease extent (n; pancolitis/left-sided/proctitis/other)	113/76/79/7
Duration of UC (years)	8.1 ± 8.4
BMI (kg/m2)	22.49 ± 4.52
Current smoking (%)	18 (6.6)
Current drinking (%)	115 (41.8)
Medication for UC
5-aminosalicylates (%)	252 (91.6)
Prednisolone (%)	55 (20.0)
Thiopurines (%)	42 (15.3)
TNF-α monoclonal antibody (%)	14 (5.1)
Mayo endoscopic subscore (MES)	1.22 ± 0.91
Complete mucosal healing (MES < 1, %)	68 (24.7)
Clinical remission (%)	163 (59.3)
Number of remaining teeth (n)	24.6 ± 6.6
< 20 teeth (%)	36 (13.1)
20–27 teeth (%)	90 (32.7)
≥ 28 teeth (%)	149 (54.2)
Frequency of tooth brushing (n)	2.1 ± 0.7
≤ 1 time/day (%)	65 (23.6)
2 times/day (%)	129 (46.9)
≥ 3 times/day (%)	81 (29.5)

BMI body mass index, UC ulcerative colitis, SD standard deviation, TNF tumor necrosis factor, Other: right-sided, segmental colitis, and postoperative patients (lack of any preoperative medical records for postoperative patients)

Table 2 shows clinical characteristics stratified by MH. Patients with MH were older, had a longer duration of UC, and showed a markedly higher prevalence of CR than those without MH. Prednisolone use was significantly lower in the MH group, suggesting lower disease activity.

Table 2.

Clinical characteristics stratified by MH

Variables	MH (+), (n = 68)		MH (−), (n = 207)	P value
Age (years)	53.9 ± 15.6	49.3 ± 15.8		0.037
Male (%)	39 (57.4)	121 (58.5)		0.873
Duration of UC (years)	10.5 ± 10	8.1 ± 8.4		0.018
BMI (kg/m2)	22.00 ± 3.47	22.65 ± 4.81		0.222
Current smoking (%)	3 (4.4)	15 (7.3)		0.001
Current drinking (%)	30 (44.1)	85 (41.1)		0.658
Medication for UC
5-aminosalicylates (%)	60 (88.2)	192 (92.8)		0.243
Prednisolone (%)	5 (7.4)	50 (24.2)		0.003
Thiopurines (%)	9 (13.2)	33 (15.9)		0.590
TNF-α monoclonal antibody (%)	2 (2.9)	12 (5.8)		0.353
Clinical remission (%)	67 (98.5)	96 (46.4)		0.001
Number of remaining teeth (n)	23.9 ± 7.1	24.9 ± 6.4		0.322
< 20 teeth (%)	11 (16.2)	25 (12.1)
20–27 teeth (%)	25 (36.8)	65 (31.4)
28 teeth (%)	32 (47.1)	117 (56.5)		0.172
Frequency of tooth brushing (n)	2.0 ± 0.0	2.0 ± 0.0		0.319
≤ 1 time/day (%)	10 (14.7)	55 (26.6)
2 times/day (%)	32 (47.1)	97 (46.9)
≥ 3 times/day (%)	26 (38.2)	55 (26.6)		0.021

BMI Body Mass Index, UC ulcerative colitis, SD standard deviation, TNF tumor necrosis factor

Table 3 presents the crude and adjusted ORs and 95% CIs for the associations between the number of remaining teeth and clinical outcomes. MH (MES = 0) and CR rates by number of remaining teeth were 30.6% and 69.4% for < 20 teeth, 27.8% and 60.0% for 21–27 teeth, and 21.5% and 56.4% for 28 teeth, respectively. Remaining teeth were not associated with MH or CR.

Table 3.

Crude and adjusted odds ratios and 95% confidence intervals for the associations between number of remaining teeth and clinical outcomes

Variable	Prevalence, n/n (%)	Crude OR (95% CI)	Adjusted OR (95% CI)
Complete MH (MES 0)
Number of remaining teeth
< 20 teeth	11/36 (30.6)	1.00	1.00
20–27 teeth	25/90 (27.8)	1.61 (0.70–3.56)	1.23 (0.44–3.34)
28 teeth	32/149 (21.5)	1.41 (0.76–2.57)	1.26 (0.63–2.51)
p for trend			0.600
Clinical remission
Number of remaining teeth
< 20 teeth	25/36 (69.4)	1.00	1.00
20–27 teeth	54/90 (60.0)	1.76 (0.82–3.97)	1.15 (0.45–3.02)
28 teeth	84/149 (56.4)	1.16 (0.68–1.98)	0.89 (0.48–1.64)
p for trend			0.933

Odds ratios were adjusted for sex, age, Body Mass Index, current drinking, and current smoking, OR odds ratio, CI confidence interval, MH mucosal healing, MES Mayo Endoscopic Score

Table 4 presents the crude and adjusted ORs and 95% CIs for the associations between frequency of toothbrushing and clinical outcomes. MH (MES 0) and CR rates by toothbrushing frequency were 15.4% and 60.0% for ≤ 1 time/day, 24.8% and 54.3% for 2 times/day, and 32.1% and 66.7% for ≥ 3 times/day, respectively. After adjustment, toothbrushing frequency was independently and positively associated with MH but not CR (adjusted odds ratio: 2.87 [95% CI: 1.19–7.29], p for trend = 0.021).

Table 4.

Crude and adjusted odds ratios and 95% confidence intervals for the associations between frequency of tooth brushing and clinical outcomes

Variable	Prevalence, n/n (%)	Crude OR (95% CI)	Adjusted OR (95% CI)
Complete MH (MES 0)
Frequency of tooth brushing
≤ 1 time/day	10/65 (15.4)	1.00	1.00
2 times/day	32/129 (24.8)	1.81 (0.85–4.15)	1.87 (0.85–4.36)
≥ 3 times/day	26/81 (32.1)	2.60 (1.18–6.13)	2.87 (1.19–7.29)
p for trend			0.021
Clinical remission
Frequency of tooth brushing
≤ 1 time/day	39/65 (60.0)	1.00	1.00
2 times/day	70/129 (54.3)	0.79 (0.43–1.44)	0.79 (0.42–1.48)
≥ 3 times/day	54/81 (66.7)	1.33 (0.68–2.64)	1.28 (0.60–2.72)
p for trend			0.491

Odds ratios were adjusted for sex, age, body mass index, current drinking, and current smoking. OR odds ratio, CI confidence interval, MH mucosal healing, MES Mayo Endoscopic Score

Discussion

In this study, we demonstrated that a high frequency of toothbrushing was independently associated with MH in patients with UC, whereas the number of remaining teeth showed no such association. In addition, toothbrushing frequency was not associated with CR. These findings suggest that daily oral hygiene behavior, rather than the structural condition of dentition, may influence intestinal mucosal recovery in UC, potentially through modulation of systemic and mucosal inflammation.

In epidemiological studies, the number of teeth is associated with cardiovascular disease [21, 22], stroke [21], and mortality [20, 22, 23]. Especially, several epidemiological studies have demonstrated that having fewer than 20 teeth is associated with all-cause mortality [22, 24].

Evidence regarding the association between the number of teeth and IBD is limited, while the meta-analysis of periodontitis in IBD showed a close association between periodontitis and IBD including UC. In a Danish study of patients with IBD, individuals with CD had fewer teeth than those with UC and fewer than 20 remaining teeth were associated with greater IBD disease activity [13]. In a Denmark case–control study of 4537 participants (including 527 patients with CD and 566 with UC), both UC and CD were associated with a higher prevalence of severe periodontitis and poor self-rated oral health compared with controls, and the proportion of individuals with fewer than 20 remaining teeth was higher among patients with CD than among those with UC [14]. Within IBD, CD tends to be associated with fewer remaining teeth, and the impact of tooth loss on disease activity appears to be more pronounced in CD, whereas studies have not consistently demonstrated a clear association in UC. Therefore, our findings regarding the number of remaining teeth may be considered broadly consistent with the existing literature.

Toothbrushing frequency is inversely associated with the incidence of chronic diseases, including hypertension [25], diabetes [26], cardiovascular disease [27], and cancer [28] in previous epidemiological studies. Some studies show an association between toothbrushing frequency and onset of IBD. In a Korean national health insurance database study, high frequency toothbrushing (≥ 3 times a day) is inversely associated with the incidence of CD, but not UC [15]. On the other hand, in a US case–control study of IBD (26 UC, 57 CD, and 54 healthy cases), the frequency of toothbrushing in IBD cases is higher than in controls [16].

Several biological mechanisms may explain this association. The oral–gut axis describes the ectopic colonization of oral bacteria within the intestinal tract, where they may exacerbate intestinal inflammation. Studies have shown that oral pathobionts such as Fusobacterium nucleatum and Porphyromonas gingivalis can migrate to the gut and promote colitis by activating immune pathways and disrupting the epithelial barrier [2, 3]. Atarashi et al. further confirmed that oral bacteria can directly drive intestinal inflammation [29]. Toothbrushing might improve indirectly and directly the mucosal inflammation via preventing dissemination of bacterial endotoxins and inflammatory mediators from the oral cavity and stopping migration of oral pathobionts to the gut [3, 6, 7, 29].

The lack of association between the number of remaining teeth and MH in this study may indicate that structural dental status reflects past oral disease rather than current inflammatory activity. Our study also found no association between toothbrushing frequency and CR. This discrepancy highlights the well-recognized dissociation between clinical symptoms and endoscopic inflammation in UC. MH reflects objective resolution of intestinal inflammation and has been associated with improved long-term outcomes, including reduced hospitalization and colectomy rates [18]. In contrast, clinical remission is influenced by subjective symptoms, which may persist despite endoscopic improvement [30]. Therefore, oral hygiene may preferentially affect mucosal inflammation without necessarily producing immediate symptomatic benefit. From a clinical perspective, these results suggest that promoting oral hygiene, a simple and non-invasive intervention, might contribute to intestinal mucosal recovery in UC. Regular toothbrushing may therefore represent an adjunctive, patient-centered strategy to optimize mucosal outcomes alongside standard pharmacological therapy.

Several limitations should be acknowledged. First, the cross-sectional design precludes causal inference, and reverse causality cannot be excluded; patients with MH may be more likely to engage in health-promoting behaviors. Second, oral microbiome composition and inflammatory biomarkers were not assessed, limiting mechanistic interpretation. Third, other oral health practices, such as professional dental care and use of antiseptic mouthwash, were not evaluated. Toothbrushing frequency was assessed using a self-administered questionnaire, and information on toothbrushing quality, brushing methods, and interdental cleaning was not available. Therefore, toothbrushing frequency may partly reflect general self-care behavior or health consciousness rather than oral hygiene status itself. Although the association remained after adjustment for lifestyle factors such as smoking and alcohol consumption, residual confounding cannot be excluded. Fourth, no prior studies have investigated the association between tooth number, brushing frequency and MH. The required sample size could not be determined in advance. Fifth, toothbrushing habits were assessed using self-reported information; therefore, social desirability bias may have led to misclassification of toothbrushing habits. However, if such misclassification occurred independently of MH status, it would likely have biased the observed association toward the null. Finally, there are limitations in generalizing the study population. Thus, the study population may not be fully representative of all Japanese UC patients. Nevertheless, the mean age, sex ratio, and medication use in this study were comparable to those reported in Japanese national UC surveys [31].

In conclusion, the present study identified a significant association between frequent toothbrushing and MH in patients with UC. These findings suggest that oral hygiene may be linked to intestinal inflammatory status through the oral–gut axis. Maintaining good oral hygiene could represent a simple and potentially modifiable factor in the comprehensive management of UC. However, it remains unclear whether toothbrushing frequency itself directly contributes to mucosal healing or whether it reflects broader oral hygiene and self-care behaviors. Further prospective studies are warranted to clarify the causal relationship and underlying mechanisms.

Author Contributions

All authors agree with the content of the manuscript. Sen Yagi and Shinya Furukawa contributed to the conception and design; Sen Yagi, Shinya Furukawa, and Teruki Miyake contributed to the investigation; Shinya Furukawa performed the formal analysis and visualization; Teruki Miyake, Eiji Takeshita, and Yoshio Ikeda contributed to data curation; Sen Yagi and Shinya Furukawa drafted the manuscript. Teruki Miyake, Osamu Yoshida, Kazuhiro Tange, Shogo Kitahata, Tomoyuki Ninomiya, Seiyuu Suzuki, Naozumi Shibata, Masakazu Hanayama, Katsuhisa Ohashi, Hideomi Tomida, Yasunori Yamamoto, Eiji Takeshita, and Yoshio Ikeda revised the manuscript critically for important intellectual content. Yoichi Hiasa contributed to the conception and design and provided supervision. Shinya Furukawa, Eiji Takeshita, Yoshio Ikeda, and Yoichi Hiasa contributed to project administration. All authors gave final approval of the version to be published, agreed on the journal to which the article has been submitted, and agreed to be accountable for all aspects of the work.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

The authors declare no competing interests.

Ethical approval

This study was approved by the Ethics Committee of Ehime University. All procedures involving human participants were conducted in accordance with the Declaration of Helsinki.

Informed consent

Written informed consent was obtained from all patients prior to sample collection.