Periodontal infections are common problem in general populations, particularly in patients with inborn errors of immunity (IEI). The disease is chronic and deliberating, resulting in reduced quality of life. Due to limited understanding of oral characteristics of the IEI patients, the aims of this project were to investigate genetic variants, phenotypes, plaque microbiome, and salivary proteome of IEI and periodontitis patients using exome/genome sequencing, metagenomic sequencing, mass spectrometry, and bioinformatics. Seventy participants: 15 IEI, 15 periodontitis, and 45 healthy were recruited. Seventy-five plaque DNA, 75 salivary samples, 75 metagenome data, and 75 proteomics data were obtained. This project showed that the IEI patients had poor oral hygiene and gingival inflammation. Genetic variants in BTK, CD40LG, FERMT3, STAT3, ELANE, TTC37, and NCF1, and chromosome 22q11.2 deletion were identified. The diseases diagnosed such as X-linked agammaglobulinemia, hyper-IgM syndrome, leukocyte adhesion deficiency, and congenital neutropenia. Metagenomics revealed that IEI patients had alterations in oral microbe composition, alpha-diversity, and beta-diversity. Bacterial species that were significantly increased in IEI: T. denticola, S. gordonii, S. oralis, Actinomyces, and V. parvula were pathogenic species also observed in periodontitis patients. Moreover, salivary proteins, particularly those related to bacterial defense, host immunity, and glycolysis, were significantly changed in IEI and periodontitis patients. In summary, this project demonstrates IEI-causing variants, microbiome dysbiosis, and disturbed salivary proteome in IEI and periodontitis patients. The study expands understanding of genotype and phenotype of IEI, leading to identification of biomarkers of periodontal diseases and impaired immunity. We provide genetic counselling and personalized oral care to the patients and families, publish international papers, groom researchers and students, build network, and distribute knowledge in international conferences and organizations. The project produces outputs/outcomes in academics, research, community, and health care that will lead to utilization of research in policy-making in the future.