In-depth Exploration of the Prevalence, Genetic, and Microbiome Profile of Indian Population with Varying Severity of Periodontitis

Periodontal disease is a prevalent and complex immunoinflammatory disease affecting the oral cavity and has proven to be a risk factor for many systemic diseases. It is one of the major global health challenges and is considered the 11th most common disease worldwide (Tonetti et al., 2017). In India, approximately 80–90% of Indians suffer from some form of periodontal disease (Chandra et al., 2016; Shaju et al., 2011). Periodontal disease starts as inflammation of the gums (gingivitis), which later progresses to the underlying bone and soft tissues, resulting in periodontitis (PD). According to the current classification of periodontal diseases and conditions, (Caton et al., 2018), PD is classified according to its severity (by staging) and rate of progression (by grading). A severe form of PD manifests as advanced generalized bone loss. early tooth loss, pain, mobility of teeth, pus discharge, swelling, and severe gingival inflammation. This severe and rapidly progressing form of PD significantly impacts about 11.2% of the global population (Marcenes et al., 2013; Tonetti et al., 2017). Although microbial plaque remains the primary etiology of PD, a severe form of PD. characterized by phenotypes (Stages III and IV) with a rapid rate of progression (Grade C) is known to have a genetic etiology. This form of PD, which is typically early-onset (EO-PD), starts in children and adolescents and progresses at a rapid rate with early loss of teeth and edentulism. In such genetically predisposed individuals, PD develops independently of common extrinsic risk factors such as smoking, systemic diseases, and the nature of the microbiome. This indicates that EO-PD is largely caused by intrinsic genetic factors with strong penetrance. Studies have shown that for this form of PD, the heritability for bone loss is estimated to be 0.4–0.5, and the heritability increases with younger individuals with EO-PD (Nibali et al., 2019). Notably, the genetic variants found to be causative for the disease in the young can also be used to identify susceptibility factors leading to massive bone destruction and tooth loss in adult PD (Fuchsberger et al., 2016; Genovese et al., 2016). A previous study identified deleterious putative causative mutations in the affected siblings, indicating important disease-relevant genes. Notably, some of these high-impact rare variants were also located within risk genes associated with common forms of PD (Richter et al., 2022). Based on this previous work, the proposed study aims to determine the prevalence of varying severity of PD in the Indian population, according to the 2017 classification of periodontal disease. The study also aims to identify rare susceptibility variants of rapidly progressive severe (Stage III/IV grade C) PD in Indian descent (EO-PD) The study also aims to correlate the genetic variants and periodontal conditions that run in their families with siblings. The study will help to understand the genetic factors responsible for severe bone loss and rapidly spreading inflammation in such individuals. In addition, it is of great interest to investigate the microbial profile in the rapidly progressive nature of PD. Currently, our understanding of PD is limited to the role of specific pathogenic oral bacteria, but a comprehensive analysis of the microbial profile could provide insight into the dynamic and aggressive nature of one of the most prevalent diseases affecting mankind today.