Yue Cai
Yanqin Zhao2†
Yongbo Kang
Ying Yang- 1Department of Endocrinology, Affiliated Hospital of Yunnan University, Kunming, China
- 2Department of Microbiology and Immunology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China
Allergic diseases have become a primary public health issue in a moderately prosperous society. Colonization of microorganisms early in life appears to be significant in guiding the regulation of childhood immune system maturation and allergy development. Since the oral cavity is the first position where most foreign antigens meet the immune system, the oral microbiota may play a key role in the development of allergies. However, the study on the effects of oral microorganisms on allergy/asthma is very restricted and should be actively investigated. It requires considerable effort to enrich our knowledge in this area of the relationship between the oral cavity and allergy/asthma. To promote the rapid progress of relevant research. In this review, we aimed to provide several insights into the role of the oral microbiota in allergy/asthma while prospecting future directions.
Allergy/asthma has become a major global public health problem (Masoli et al., 2004; Barnett and Nurmagambetov, 2011; Accordini et al., 2013; Strachan et al., 2022). Colonization of microorganisms early in life appears to be significant in guiding the regulation of childhood immune system maturation and allergy development (Jenmalm, 2017; Kang et al., 2017; Kang and Cai, 2018). In the initial stage, the microbial composition of different ecological niches in the neonatal body is highly similar to each other (Dominguez-Bello et al., 2010). Then, the niche-specific establishment of the microbiota occurs and increases complexity as the immune system matures (Gensollen et al., 2016). Growing evidence suggests a strong relationship between dysbacteriosis in infancy and the development of allergy in childhood (Kang et al., 2017; West et al., 2017). Several factors have been identified as having the ability to influence the composition of the microbiome, possibly leading to the development of allergic diseases in children (Johnson et al., 2005; Guaraldi and Salvatori, 2012; Stensballe et al., 2013; Jakobsson et al., 2014). For instance, first-trimester maternal use of antimicrobials during pregnancy, cesarean delivery, formula feeding, and antimicrobial exposure.
The majority of current research describes microbial colonization in the gut, but there are signs that microbial colonization of the skin and respiratory tract might be related to allergy/asthma (Kong et al., 2012; Huang, 2015; Kang et al., 2017; Kennedy et al., 2017; Kang and Cai, 2018). Although some studies have shown the presence of bacterial dysbiosis and reduced microbial diversity prior to allergy/asthma attacks (Teo et al., 2015; Dzidic et al., 2017; Kang et al., 2017), other studies are comparing microbiota differences between allergic and healthy children (Kang et al., 2017). Altogether, gut, nasopharyngeal, and skin microbial dysbiosis has been connected with abnormal development of immune responses and allergy/asthma (Teo et al., 2015; Dzidic et al., 2017; Kang et al., 2017; Kennedy et al., 2017).
However, the impact of oral bacteria on allergy/asthma development is still poorly understood. The importance of the oral microbiome (i.e., all microbes that exist in the oral cavity and their collective genome) and its association with the status of health and disease has been recognized only in recent years (Zarco et al., 2012). Nowadays, a growing body of evidence has shed light on the association of dysbiosis of oral microbiota with oral (e.g., dental caries, periodontal disease, etc.), respiratory (e.g., chronic obstructive pulmonary diseases, pneumonia, etc.), neurological (e.g., Parkinson's Disease, Alzheimer's disease, etc.), and metabolic diseases (e.g., obesity, diabetes, non-alcoholic fatty liver disease, etc.), cancer (e.g., oral, lung, gastrointestinal tract and esophageal, gastric, pancreatic, colorectal cancers), autoimmune diseases (rheumatoid arthritis), cardiovascular diseases, and so on (Le Bars et al., 2017; Saeb et al., 2019; Shen, 2020; Xu et al., 2020; Pathak et al., 2021; Tuominen and Rautava, 2021; Zapała et al., 2022). Furthermore, certain oral microbial strains have been shown to inhibit or attenuate immune responses, suggesting that specific species among oral commensal bacteria may play either a pathogenic or a protective role in the development of these diseases. The qualitative and quantitative intricacy of the oral microbial community makes it the second most variedbacterial community in the human body after the gut (Zhang et al., 2018). About 700 common microorganisms have been tested in the oral cavity (Dewhirst et al., 2010; Zarco et al., 2012; Gholizadeh et al., 2016). Meanwhile, the most prevalent and abundant oral bacterial species-level taxa fall into eight phyla: Firmicutes, Fusobacteria, Bacteroidetes, Actinobacteria, Proteobacteria, Spirochaetes, Synergistetes, and TM7 (Kazor et al., 2003; Keijser et al., 2008; Siqueira and Rôças, 2017; Yamashita and Takeshita, 2017). Usually, the commensal microbiota here has a symbiotic relationship with the host. However, in some cases, some microorganisms can overcome the host's defenses and become pathogenic bacteria (Sampaio-Maia et al., 2016). For neonates, the bacterial communities in the oral cavity and other body habitats are of striking resemblance to each other within 5 min after birth (Dominguez-Bello et al., 2010). The type of organism is strongly determined by the mode of delivery. Furthermore, the mother's mouth microbiota is the most significant source for the success of vertical transmission of the oral bacterial in infants and young children (Zaura et al., 2014; Wang et al., 2022). With age, infants and children develop a great variety of oral microbes due to diverse diets, lifestyles, environments, and other factors (Al-Shehri et al., 2016).
Since the oral cavity is the immune system's first line of defense against most foreign antigens, there is reason to trust that the oral microbiota may play a key role in the development of allergies. Little research has been published on the relationship between oral microorganisms and allergies. Only one study showed changes in the relative abundance of “beneficial” and potentially “harmful” bacteria in children with allergy/asthma compared to healthy subjects (Table 1). By using a culture-independent next generation sequencing approach to assess longitudinal development of oral microorganisms in infancy and childhood in saliva samples from children who developed allergies and children who remained healthy until 7 years of age, Dzidic et al. (Dzidic et al., 2018) found that children with allergic diseases, especially asthma, had lower saliva bacterial diversity and had a highly varied bacterial composition at age 7 years, suggesting that these individuals had marked changes in their oral microbiota, possibly caused by damage to the immune system in infancy. Furthermore, the relative abundance of some microbic species, including Gemella haemolysans, increased in children with allergies, and the abundance of Lactobacillus gasseri and L. crispatus in healthy children was unique in early infancy, which may affect early immunity maturation. Therefore, early changes of composition in oral microorganisms appear to affect immune maturation and allergy development. In conclusion, this study shows that the oral microbiota is strongly associated with the development of allergy/asthma. In line with this observation, MSc et al. (Espuela-Ortiz et al., 2019) also found that children with asthma have a lower relative abundance for Streptococcus genus and higher Veillonella genus compared with healthy children. In conclusion, this study identified changes in the salivary microbiota associated with asthma.
Table 1. Changes in oral microbiota composition associated with allergy/asthma.
Recently, by analyzing bacterial microbiota profiles in induced sputum and oral wash samples from subjects with mild atopic asthma, atopic non-asthmatic subjects, and non-atopic healthy subjects, Durack et al. (Durack et al., 2020) found that sputum bacterial burden was inversely associated with bronchial expression of type 2 (T2)-related genes. Differences in specific sputum microbiota are also associated with T2-low asthma phenotypes, a subgroup of whom displayed elevations in lung inflammatory mediators and reduced sputum bacterial diversity. Differences in specific oral microbiota were more reflective of atopic status. After inhaled corticosteroid (ICS) treatment of asthmatics, the compositional structure of sputum microbiota showed greater deviation from baseline in ICS non-responders than in ICS-responders. Altogether, novel associations of sputum and oral microbiota to immunologic features were observed in this cohort of subjects with or without ICS-naïve mild asthma.
However, the available data are greatly limited in this area, and correlational studies are needed. It is necessary to have a thorough understanding of the mechanism of action between gut microbiota and allergy/asthma. It is therefore clear that a large number of studies should be done in different populations or mammalian models. Meanwhile, more concern and more research are essential to the potential immunomodulatory role of oral microbes. Moreover, we should also be centered on identifying the best bacterial biomarkers to predict allergy and asthma risk in future research. Last but not least, future experiments should also isolate some potential beneficial bacteria and investigate their role in improving allergy and asthma.
Data Availability Statement
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.
Author Contributions
YC and YZ collected the data and wrote most of the manuscript with help from YK and YY. All authors contributed to the article and approved the submitted version.
Funding
This work was supported by the Science Research Start-up Fund for Doctor of Shanxi Medical University (Grant No. XD1807), Science Research Start-up Fund for Doctor of Shanxi Province (Grant No. SD1807), Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi (Grant No. 2019L0425), and Shanxi Province Science Foundation for Youths (Grant No. 201901D211314).
Conflict of Interest
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.
Publisher's Note
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References
Accordini, S., Corsico, A., and Braggion, M. (2013). The cost of persistent asthma in Europe: an international population-based study in adults. Int. Arch. Allergy Immunol. 160, 93–101. doi: 10.1159/000338998
Al-Shehri, S., Sweeney, E., and Cowley, D. (2016). Deep sequencing of the 16S ribosomal RNA of the neonatal oral microbiome: a comparison of breast-fed and formula-fed infants. Sci. Rep. 6, 38309. doi: 10.1038/srep38309
Barnett, S., and Nurmagambetov, T. A. (2011). Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 127.145–152. doi: 10.1016/j.jaci.2010.10.020
Dewhirst, F. E., Chen, T., and Izard, J. (2010). The human oral microbiome. J. Bacterial. 192, 5002–5017. doi: 10.1128/JB.00542-10
Dominguez-Bello, M., Costello, E., and Contreras, M. (2010). Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA. 107, 11971–11975. doi: 10.1073/pnas.1002601107
Durack, J., Christian, L. S., and Nariya, S. (2020). Distinct associations of sputum and oral microbiota with atopic, immunologic, and clinical features in mild asthma. J. Allergy Clin. Immunol. 146, 1016–1026. doi: 10.1016/j.jaci.2020.03.028
Dzidic, M., Abrahamsson, T., and Artacho, A. (2018). Oral microbiota maturation during the first 7 years of life in relation to allergy development. Allergy. 73, 2000–2011. doi: 10.1111/all.13449
Dzidic, M., Abrahamsson, T. R., and Artacho, A. (2017). Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development. J. Allergy Clin. Immunol. 139, 1017–1025.e14. doi: 10.1016/j.jaci.2016.06.047
Espuela-Ortiz, A., Lorenzo-Diaz, F., and Baez-Ortega, A. (2019). Bacterial salivary microbiome associates with asthma among african american children and young adults. Pediatr. Pulmonol. 54, 1948–1956. doi: 10.1002/ppul.24504
Gensollen, T., Iyer, S. S., and Kasper, D. L. (2016). How colonization by microbiota in early life shapes the immune system. Science. 352, 539–544. doi: 10.1126/science.aad9378
Gholizadeh, P., Eslami, H., and Yousefi, M. (2016). Role of oral microbiome on oral cancers, a review. Biomed. Pharmacother. 84, 552–558. doi: 10.1016/j.biopha.2016.09.082
Guaraldi, F., and Salvatori, G. (2012). Effect of breast and formula feeding on gut microbiota shaping in newborns. Front Cell Infect. Microbiol. 2, 94. doi: 10.3389/fcimb.2012.00094
Huang, Y. J.. (2015). The respiratory microbiome and innate immunity in asthma. Curr Opin Pulm Med. 21, 27–32. doi: 10.1097/MCP.0000000000000124
Jakobsson, H., Abrahamsson, T., and Jenmalm, M. (2014). Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 63, 559–566. doi: 10.1136/gutjnl-2012-303249
Jenmalm, M. C.. (2017). The mother-offspring dyad, microbial transmission, immune interactions and allergy development. I Intern Med. 282, 484–495. doi: 10.1111/joim.12652
Johnson, C., Ownby, D., and Alford, S. (2005). Antibiotic exposure in early infancy and risk for childhood atopy. J. Allergy Clin. Immunol. 115, 1218–1224. doi: 10.1016/j.jaci.2005.04.020
Kang, Y., and Cai, Y. (2018). Future prospect of faecal microbiota transplantation as a potential therapy in asthma. Allergol. Immunopathol. 46, 307–309. doi: 10.1016/j.aller.2017.04.008
Kang, Y., Cai, Y., and Zhang, H. (2017). Gut microbiota and allergy/asthma: from pathogenesis to new therapeutic strategies. Allergol. Immunopathol. 45, 305–309. doi: 10.1016/j.aller.2016.08.004
Kazor, C. E., Mitchell, P. M., and Lee, A. M. (2003). Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients. J. Clin. Microbiol. 41, 558–563. doi: 10.1128/JCM.41.2.558-563.2003
Keijser, B. J., Zaura, E., and Huse, S. M. (2008). Pyrosequencing analysis of the oral microflora of healthy adults. J Dent Res. 87, 1016–1020. doi: 10.1177/154405910808701104
Kennedy, E. A., Connolly, J., and Hourihane, J. O. (2017). Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2months is associated with a lower risk of atopic dermatitis at 1 year. J. Allergy Clin. Immunol. 139, 166–172. doi: 10.1016/j.jaci.2016.07.029
Kong, H. H., Oh, J., and Deming, C. (2012). Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 22, 850–859. doi: 10.1101/gr.131029.111
Le Bars, P., Matamoros, S., and Montassier, E. (2017). The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract. Can J Microbiol. 63, 475–492. doi: 10.1139/cjm-2016-0603
Masoli, M., Fabian, D., and Holt, S. (2004). The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 59, 469–478. doi: 10.1111/j.1398-9995.2004.00526.x
Pathak, J., Yan, Y., and Zhang, Q. (2021). The role of oral microbiome in respiratory health and diseases. Respir. Med. 185, 106475. doi: 10.1016/j.rmed.2021.106475
Saeb, A. T. M., Al-Rubeaan, K. A., and Aldosary, K. (2019). Relative reduction of biological and phylogenetic diversity of the oral microbiota of diabetes and pre-diabetes patients. Microb. Pathog. 128, 215–229. doi: 10.1016/j.micpath.2019.01.009
Sampaio-Maia, B., Caldas, I. M., and Pereira, M. L. (2016). The oral microbiome in health and its implication in oral and systemic diseases. Adv Appl Microbiol. 97, 171–210. doi: 10.1016/bs.aambs.2016.08.002
Shen, L.. (2020). Gut, oral and nasal microbiota and Parkinson's disease. Microb. Cell Fact. 19, 50. doi: 10.1186/s12934-020-01313-4
Siqueira, J. F., and Rôças, I. N. (2017). The oral microbiota in health and disease: an overview of molecular findings. Methods Mol. Biol. 1537, 127–138. doi: 10.1007/978-1-4939-6685-1_7
Stensballe, L., Simonsen, J., and Jensen, S. (2013). Use of antibiotics during pregnancy increases the risk of asthma in early childhood. 162, 832–838.e3. doi: 10.1016/j.jpeds.2012.09.049
Strachan, D., Rutter, C., and Asher, M. (2022). Worldwide time trends in prevalence of symptoms of rhinoconjunctivitis in children: Global Asthma Network Phase I. Pediatr. Allergy Immunnol. 33, e13656. doi: 10.1111/pai.13656
Teo, S., Mok, D., and Pham, K. (2015). The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host. Microbe. 17, 704–715. doi: 10.1016/j.chom.2015.03.008
Tuominen, H., and Rautava, J. (2021). Molecular biology c. oral microbiota and cancer development. Pathobiology. 88, 116–126. doi: 10.1159/000510979
Wang, T., Ishikawa, T., Sasaki, M., and Chiba, T. (2022). Oral and gut microbial dysbiosis and non-alcoholic fatty liver disease: the central role of Porphyromonas gingivalis. Front. Med. (Lausanne). 9, 822190. doi: 10.3389/fmed.2022.822190
West, C. E., Christina, E., and Prescott, S. L. (2017). Bugging allergy; role of pre-, pro- and synbiotics in allergy prevention. Allergol Int. 66, 529–538. doi: 10.1016/j.alit.2017.08.001
Xu, Y., Zhang, M., and Zhang, J. (2020). Differential intestinal and oral microbiota features associated with gestational diabetes and maternal inflammation. Am. J. Physiol. Endocrinol. Metab. 319, E247–E253. doi: 10.1152/ajpendo.00266.2019
Yamashita, Y., and Takeshita, T. (2017). The oral microbiome and human health. J. Oral Sci. 59, 201–206. doi: 10.2334/josnusd.16-0856
Zapała, B., Stefura, T., and Milewicz, T. (2022). The role of the western diet and oral microbiota in parkinson's disease. Nutrients. 14, 355. doi: 10.3390/nu14020355
Zarco, M. F., Vess, T. J., and Ginsburg, G. S. (2012). The oral microbiome in health and disease and the potential impact on personalized dental medicine. Oral Dis. 18.109–120. doi: 10.1111/j.1601-0825.2011.01851.x
Zaura, E., Nicu, E., and Krom, B. (2014). Acquiring and maintaining a normal oral microbiome: current perspective. Front. Cell Infect. Microbiol. 4, 85. doi: 10.3389/fcimb.2014.00085
Keywords: children, oral microbiota, immunity, allergy, asthma
Citation: Cai Y, Zhao Y, Kang Y and Yang Y (2022) Future Prospect of Oral Microbiota Influencing Allergy/Asthma Development. Front. Microbiol. 13:875664. doi: 10.3389/fmicb.2022.875664
Received: 14 February 2022; Accepted: 14 April 2022;
Published: 30 May 2022.
Edited by:
Luigina Romani, University of Perugia, ItalyReviewed by:
Claudio Costantini, University of Perugia, ItalyCopyright © 2022 Cai, Zhao, Kang and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ying Yang, eWFuZ3lpbmcyMDcyJiN4MDAwNDA7MTI2LmNvbQ==; Yongbo Kang, NjU3MTUxMjc2JiN4MDAwNDA7cXEuY29t
†These authors have contributed equally to this work