First large-scale epidemiological study in Asia reveals link between parental saliva contact and risk of developing allergic diseases

Kanazawa Nobuo, professor in charge of Department of Dermatology Hyogo Medical University (located in Nishinomiya, Hyogo Prefecture; President: Suzuki Keiichiro), and a joint research group from Wakayama Medical University, Dokkyo Medical University, and Takatsuki Red Cross Hospital conducted a large-scale survey of Japanese school-age children and their parents and found that "contact with saliva during infancy is associated with a reduced risk of developing allergies during school age."

Saliva Contact During Infancy and Allergy Development in School-Age Children

Yoshimi Kubo (*1)(★), Nobuo Kanazawa (*1) (*2), Hironobu Fukuda (*3), Yutaka Inaba (*1), Naoya Mikita (*1), Masatoshi Kamito (*1), Fukumi Furukawa (*1) (*4), Yasushi Kuraishi (*5), Shigemi Yoshihara (*3)
* (★) Corresponding author, (1) Department of Dermatology, Wakayama Medical University, (2) Hyogo Medical University Department of Dermatology, (3) Dokkyo Medical University Department of Pediatrics, (4) Department of Dermatology, Takatsuki Red Cross Hospital, (5) Division of Industry-Academia Collaboration Promotion Headquarters, Wakayama Medical University

In recent years, the number of allergic diseases in children has increased, and preventive measures are urgently needed. A birth cohort study in Sweden by Hasselmar et al. published in 2013 suggested that the transfer of oral bacteria from parents to children via cleaning of pacifiers with parental saliva in infancy may stimulate the infant's immune system, leading to effective allergy prevention in infancy. However, there have been few studies examining the onset of allergies and their associations in school-age children. Therefore, our research group conducted a large-scale epidemiological survey in Ishikawa and Tochigi prefectures, the first in Asia, targeting Japanese school-age children and their parents, and analyzed the association between saliva contact through sharing tableware and cleaning of pacifiers with parental saliva in infancy and the risk of developing eczema (atopic dermatitis), allergic rhinitis, and asthma in elementary and junior high school students. As a result, it was found that saliva contact through sharing tableware in infancy was significantly associated with a lower risk of developing eczema (atopic dermatitis) in school-age children. In addition, contact with saliva via cleaning pacifiers with parental saliva was significantly associated with a lower risk of developing eczema (atopic dermatitis) and allergic rhinitis in school-age children. Furthermore, for school-age asthma, although no clear significant differences were found in this study, it was possible to speculate on the possibility of a "lower risk of developing" in the case of saliva contact via cleaning pacifiers with parental saliva. Further research is needed to clarify the mechanisms of these reduced allergy risk reductions and to utilize these findings to prevent the onset of eczema (atopic dermatitis), allergic rhinitis, and asthma in children.

Allergic diseases such as eczema (atopic dermatitis), allergic rhinitis, food allergies, and asthma, which have a significant impact on quality of life and place a burden on society, have been increasing worldwide in recent years, especially in developed countries. The hygiene hypothesis has been proposed as a cause of the increase in allergic diseases, which posits that the incidence of infectious diseases has decreased in clean environments such as those in developed countries, leading to research into the relationship between resident and commensal bacteria (intestinal flora) and immune development. The development of so-called allergen resistance is thought to depend on several factors, including the diversity of intestinal flora, immune stimulation by microorganisms during infancy, and acquisition of microorganisms from the mother at birth. Insufficient microbial stimulation during infancy may cause hypersensitivity of barrier tissues such as the skin, which may enhance type 2 immune responses (allergic diseases).
The oral cavity has the second richest microbiota after the digestive tract. Animal and human studies suggest that oral microbes migrate to the intestine and change the intestinal microbiota, possibly thereby altering immune defense. In 2018, Dzidic et al. reported that early changes in the composition of the oral microbiota affect immune maturation and the development of allergies. In addition, a birth cohort study in Sweden reported that the use of pacifiers washed with parents' saliva significantly reduced the risk of developing eczema (atopic dermatitis) and asthma at 18 months of age and the risk of developing eczema (atopic dermatitis) at 36 months of age. The reason for this may be that immune stimulation by oral microbes transferred from parents' saliva to infants is involved.
Previous research by our research group also suggested that feeding infants chewing their food (chewing food to soften it before feeding it to them) may reduce the risk of developing allergies in school-age, in particular the risk of developing eczema (atopic dermatitis), and suggested that "immune stimulation through the transfer of oral microorganisms from caregivers to infants may be involved."
Therefore, our research group hypothesized that contact with saliva during infancy (under 12 months of age) reduces the risk of developing allergies in Japanese children. To verify this hypothesis, we conducted a multi-center collaborative study by carrying out a "cross-sectional epidemiological survey" using 91 self-report questions, including those from the International Study of Asthma and Allergies in Childhood (ISAAC)," targeting Japanese elementary and junior high school students and their parents.

To reduce regional bias, the survey was conducted in two prefectures, Ishikawa and Tochigi. Anonymous self-administered questionnaires were distributed to students in grades 1 to 6 of elementary school and grades 1 to 3 of junior high school, and the completed questionnaires were collected at home by the students and their parents.
*Target: 1,718 students and parents from three elementary schools and three junior high schools in Ishikawa Prefecture in 2016, and 1,852 students and parents from three elementary schools and two junior high schools in Tochigi Prefecture in 2017.
* Questionnaire: ISAAC questionnaire and original questions on food allergies and oral allergies (41 questions) and 50 questions on the lifestyle or environment of the mother during pregnancy and the child during infancy, totaling 91 questions

Evaluation was performed using descriptive statistics and chi-squared or Fisher's exact tests, as appropriate.Multivariate logistic regression analysis was performed to evaluate the independent association between the onset of eczema (atopic dermatitis), allergic rhinitis, and asthma in primary and junior high school students and saliva contact via sharing eating utensils and cleaning pacifiers with parental saliva during infancy (<12 months of age).
The valid response rate was 94.7%. The mean and median ages of the children were 10.8±2.7 and 11 years (interquartile range 9-13 years), respectively.

(Research Results)
・Contact with saliva from sharing eating utensils during infancy was found to be significantly associated with a lower risk of developing eczema (atopic dermatitis) during school age (odds ratio [OR] 0.53; 95% confidence interval [CI] 0.34-0.83).
The association remained significant after adjusting for possible confounding factors (maternal history of allergies, maternal smoking during pregnancy, and parental knowledge of oral infections) (OR 0.52; 95% CI 0.32-0.84).
Contact with saliva via cleaning pacifiers with parental saliva was significantly associated with a reduced risk of developing eczema (atopic dermatitis) (OR 0.24; 95% CI 0.10-0.60) and allergic rhinitis (OR 0.33; 95% CI 0.15-0.73), and this association remained significant even after adjusting for confounding factors (OR 0.35; 95% CI 0.13-0.91 and OR 0.32; 95% CI 0.14-0.72, respectively).
- No clear significant difference was found between parental saliva cleaning of pacifiers and school-age asthma, but there was some suggestion of a possible reduced risk of developing the condition (adjusted OR 0.17; 95% CI 0.02-1.31).

In recent years, oral hygiene knowledge has become widespread, and opportunities for contact with saliva during infancy have been decreasing due to the COVID-19 pandemic. In this context, we believe that the data and analysis results obtained from this epidemiological survey are extremely valuable. We believe that further research is needed to elucidate the mechanism of reducing the risk of developing allergies in children, focusing on the oral and intestinal flora of parents and children from pregnancy and infancy, and to apply this to the prevention of eczema (atopic dermatitis), allergic rhinitis, and asthma.

Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant No. 17K09124), Joint Research Grant from the Japanese Society of Allergy and Cutaneous Immunology

Journal of Allergy and Clinical Immunology: Global