Introduction

Historically, oral health has been considered as an isolated entity, but contemporary research underscores the necessity of a more holistic approach that bridges dentistry and medicine1. The oral cavity is an integral component of the human body, and its health is deeply connected with the essence of overall well-being1,2. Oral diseases, such as caries, periodontal disease, and orofacial pains, rank among the most prevalent health issues globally, affecting approximately 3.5 billion individuals. The personal and societal burden of these oral diseases is disproportionately higher in lower- to middle-income countries, due to limited access to oral healthcare. The prevalence of oral diseases is anticipated to rise3; thus, enhancing oral health represents a critical, unmet global health need. Based on this perspective, more emphasis on integrative medicine and research is required to better understand the connections between oral and systemic health.

The oral microbiome and health

Recent studies have illuminated the profound impact of oral health on systemic conditions1,2,3. The oral microbiome is a key player in this interconnection. It represents the second largest microbial community following the gut microbiome. More than 700 oral microbial species have been identified4, and we are discovering even more species with the advancement of next-generation sequencing technologies. A healthy oral microbiome is essential for health and well-being via modulating the immune response and protecting against pathogen invasion, while dysbiosis in this microbial community contributes to both oral and systemic diseases. Research findings suggest that oral dysbiosis can contribute to systemic inflammation, thereby predisposing to diseases such as cardiovascular diseases5,6, inflammatory bowel diseases7,8, metabolic disorders9, among others. In this Collection, a study by Stankevic et al. investigated the oral microbiome through a genome-wide association study, revealing novel insights into interactions between oral bacterial communities and host genomic variations10. Salivary microbiota, analyzed via 16S rRNA sequencing in a Danish cohort of 610 adults stratified by type 2 diabetes and cardiovascular disease risks, identified host single nucleotide polymorphisms (SNPs) affecting oral microbial composition and diversity. Most identified genetic variants correlated with cardiometabolic traits, including glycated hemoglobin A1c, triglycerides, high-density lipoprotein cholesterol, type 2 diabetes, and stroke risk. These findings highlight the oral microbiome’s significance as a health determinant influenced by host genetic factors contributing to various diseases.

Oral bones, muscles, and joints

Up to 30% of the population has at least one temporomandibular disorder (TMD), and as many as 15% have a painful condition11,12. TMDs have significant implications for both general and psychological health and are multifaceted conditions with causes largely found from systemic and psychological health, i.e. unhealth. This highlights the deep link to and necessity of integrative medicine in understanding oral-systemic health connections and the necessity of a collaborative approach between medical and dental professionals13. In a prospective clinical trial published in the Collection, two different maxillomandibular relationship registration techniques for occlusal splint fabrication were randomly assessed and compared. The trial showed that the effectiveness of occlusal splints in relieving pain-related TMD-symptoms was equally good non-dependent of registration technique supporting previous findings regarding effectiveness of occlusal splints14.

In a randomized, triple-blinded clinical trial, de Souza Nobre et al. aimed to assess the effectiveness and functional adverse effects of a single compared to multiple injections of botulinum toxin-A on masseter muscle hypertrophy15. The study demonstrated that a single low-dose intervention was effective; however, multiple doses administered over short intervals resulted in adverse effects, including impaired masticatory performance and reduced muscle activity.

Additionally, the Collection included an animal study exploring the modulatory role of dietary hesperidin combined with the recombinant human bone morphogenetic protein 2 (BMP2) on craniofacial bone regeneration16. The study proved that hesperidin had a significant skeletal bone sparing effect, with potentiation of BMP-induced craniofacial regeneration.

Systemic diseases and oral health

Systemic diseases can also adversely affect oral health. For example, diabetes mellitus is associated with an increased risk of periodontal disease. Elevated blood glucose levels can lead to a higher prevalence of gum disease, creating a bidirectional relationship where each condition exacerbates the other17. Rheumatic diseases, such as rheumatoid arthritis and Sjögren’s syndrome, can cause temporomandibular joint (TMJ) degeneration, impairing chewing and compromising aesthetic appearance, which negatively impacts oral health18,19. Patients with these conditions are at increased risk for dental caries due to factors such as dry mouth, immunosuppression, and reduced hand function, which can make maintaining good oral hygiene challenging20. Collin et al. performed a prospective two-year longitudinal cohort study on children and adolescents with juvenile idiopathic arthritis18. The latter study proved TMJ-involvement due to this inflammatory disease and explored the development of TMJ-deformities over time using cone-beam computed tomography, pointing out the necessity of a collaborative approach between medical and dental professionals13.

Conclusion and future perspectives

Despite these interconnected relationships, dentistry and medicine have traditionally operated as separate disciplines with minimal overlap. Bridging this divide holds significant potential for enhancing medical practice and patient outcomes. Incorporating oral health assessments into routine medical evaluations can facilitate early detection of systemic conditions, given that many diseases manifest initial symptoms within the oral cavity. For example, oral manifestations can be early indicators of systemic diseases such as rheumatic diseases, inflammatory bowel disease, diabetes, heart problems, orofacial pains, and also certain cancers21. Furthermore, a connection has also been found even before birth; poor oral health has been linked to adverse pregnancy outcomes, including preterm birth and low birth weight. Maintaining optimal oral hygiene during pregnancy is crucial as periodontal disease can increase the risk of these complications22.

Hence, the complex relationship between oral and systemic health necessitates a paradigm shift towards integrative healthcare models. Recognizing the mouth and its associated structures as a vital component of the body underscores the importance of collaborative efforts between dental and medical practitioners. Such an approach promises to enhance patient care, improve health outcomes, and address the global health challenge posed by oral diseases. This can also pave the way for a more personalized approach for managing both oral and systemic diseases. Establishing an oral-systemic connection can lay a strong foundation for the development of novel diagnostic assays such as point-of-care tests based on salivary biomarkers, and microbiome-based signatures. These innovative assays can help in the early diagnosis and in predicting the prognosis of diseases inside and outside the oral cavity. Furthermore, this paradigm shift towards integrative healthcare models would also result in a more personalized treatment approach departing from a patient’s individual etiologies, co-existing conditions, needs, and possibilities. Thus, multidisciplinary research is indeed essential and required to achieve these goals in the future.