Thumb sucking or nail biting in childhood and adolescence is associated with an increased risk of Crohn’s disease: results from a large case–control study

Abstract

Background

The hygiene hypothesis suggests that a reduction in microbial exposure contributes to an impaired immune response later in life and increases the incidence of immune-mediated diseases such as inflammatory bowel diseases (IBD). Thumb sucking and nail biting are two early habits that modulate the oral microbiota composition and antigen load.

Objective

We hypothesized a lower risk of Crohn’s disease (CD) and ulcerative colitis (UC) in adults with prior thumb sucking and nail biting.

Methods

918 IBD cases and their 918 siblings without IBD were asked to fill out a survey containing 32 questions on environmental factors in childhood and early adulthood. Prevalence of thumb sucking and/or nail biting at the usually well-remembered time of (1) school enrollment and (2) coming-of-age ceremonies was the predefined combined risk factor of this study.

Results

65% of the patients were female and 57% suffered from CD. About 49% of IBD patients but only 44% of their siblings reported thumb sucking/nail biting at the time of school enrollment or coming-of-age (p = .007). Sensitivity analysis revealed that this difference was observed in patients with CD (50% versus 41%; RR= 1.22; 95% CI 1.09–1.37, p = .001) but not in patients with UC (49% versus 48%; RR= 1.02; 95% CI 0.90–1.17; p = .83).

Conclusion

Contrary to our expectation and challenging the hygiene hypothesis, we found that common oral habits are not protective against IBD. Instead, nail biting at the time of school enrollment and coming-of-age was a statistically significant risk factor for CD in our cohort.

Key summary

Evidence available before this study: The hygiene hypothesis suggests that a reduction in microbial exposure due to improved health activities has contributed to an immunological imbalance in the intestine and an increased incidence of allergic and autoimmune diseases. A population-based birth cohort study has demonstrated that thumb-sucking and nail biting in children lead to a reduction of the risk of atopic sensitization, asthma, and hay fever.

Added value of this study: Contrary to the hypothesis, thumb sucking and nail biting were not associated with a reduced risk of IBD. Instead, thumb sucking and/or nail biting at the usually well-remembered points in time of school enrollment and of religious or secular coming-of-age ceremonies was associated with a higher risk of Crohn’s disease but not of ulcerative colitis. Our data did not support the hygiene hypothesis, one pathogenic concept in the context of IBD.

Keywords:

• Crohn’s disease
• ulcerative colitis
• hygiene hypothesis
• gut microbiota
• thumb sucking
• nail biting

Acknowledgments

The authors thank all patients for their participation in this study and Attyla Drabik, MD, MPH, Clinical Trial Support Münster for sample size calculation.

Author contributions

N.T, T.B., A.S.: Study design and data analysis and writing up of the first draft of the paper; W.M., C.P., G.N., A.G., J.W., G. F., R. A., W. K., D. B., A. R.: Patient recruitment, K.S.:data collection, all authors: discussion and approval of the first draft of the paper.

Disclosure statement

Niels Teich has served as a speaker, a consultant, and/or an advisory board member for AbbVie, Amgen, Falk Foundation, Janssen, MSD, Norgine, Takeda, Tillotts, Vifor, and has received research funding from Ferring Arzneimittel GmbH.

Wolfgang Mohl has served as a speaker, a consultant, and/or an advisory board member for AbbVie, alanta, Amgen, Biogen, Falk Foundation, Hexal, Janssen, Pfizer, Synformulas, Takeda, and Tillotts.

Christian Primas – none declared.

Gottfried Novacek has served as a speaker, a consultant, and/or an advisory board member for AbbVie, MSD, Janssen, Pfizer, Takeda, Ferring, Falk Foundation, Astro-Pharma.

Annika Gauss has received travel fees from AbbVie, Janssen, and Tillotts, speaker’s fees from Janssen, MSD, Tillotts, and Takeda, and consultation fees from Janssen and AMGEN.

Jens Walldorf has received fees as a speaker, a consultant, and/or an advisory board member for AbbVie, Janssen, MSD, and Takeda.

Gisela Felten – none declared.

Raja Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Biogen, Boehringer Ingelheim GmbH & Co. KG, Falk Foundation, Ferring GmbH, GlaxoSmithKline plc, InDex Pharmaceuticals AG, Janssen-Cilag GmbH, MSD Sharp & Dome GmbH, Pfizer Inc., Roche Pharma, Samsung Bioepsis, Stelic Institute, Takeda GmbH & Co. KG, Tillotts Pharma AG.

Wolfgang Kruis – none declared.

Dominik Bettenworth is on the advisory board or consultant for Amgen, AbbVie, Falk Foundation, Ferring, MSD, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts Pharma, and Vifor.

Artur Roznowski has served as a speaker for AbbVie, Falk Foundation, MSD, Takeda, and Ferring Arzneimittel GmbH.

Jost Langhorst has served as a speaker, a consultant, and/or an advisory board member for Falk Foundation, Repha GmbH, Celgene GmbH; Dr Willmar Schwabe; Steigerwald Arzneimittelwerke GmbH; Ferring Arzneimittel GmbH; Sanofi, and has received research funding from Steigerwald Arzneimittelwerke GmbH, Falk Foundation; TechLab, Dr Willmar Schwabe; Repha GmbH.

Karen Schmidt – none declared.

Tony Bruns – none declared.

Andreas Stallmach has served as a speaker and advisory board member of Abbvie, Astellas, Braun, Biogen, CLS Behring, Falk Foundation, Hexal, Janssen, Medical Tribune, Mundipharma, MSD, Norgine, Pfizer, Summit Therapeutics, Takeda, Tillots Pharma.

Data availability statement

Will individual participant data be available? Yes.

What data in particular will be shared? All of the individual participant data collected during the trial, after de-identification

What other documents will be available? Study protocol, statistical analysis plan, informed consent form, clinical study report

When will data be available? Immediately following publication; no end date

With whom? Researchers who provide a methodologically sound proposal

For what types of analyses? To achieve aims formulated in the approved proposal

By what mechanism will data be made available? Proposals should be directed to Niels Teich M.D. at [email protected]; to gain access, data requestors will need to sign a data access agreement.

Additional information

Funding

This work was supported by Ferring Arzneimittel GmbH (Kiel/Germany) with a study grant of 12,000 Euros to N. T. The representatives of Ferring Arzneimittel GmbH had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication.