Dysbiosis and Alterations in Predicted Functions of the Subgingival Microbiome in Chronic Periodontitis

Abstract

Chronic periodontitis is an inflammatory disease of the periodontium affecting nearly 65 million adults in the United States. Changes in subgingival microbiota have long been associated with chronic periodontitis. Recent culture-independent molecular studies have revealed the immense richness and complexity of oral microbial communities. However, data sets across studies have not been directly compared, and whether the observed microbial variations are consistent across different studies is not known. Here, we used 16S rRNA sequencing to survey the subgingival microbiota in 25 subjects with chronic periodontal disease and 25 healthy controls and compared our data sets with those of three previously reported microbiome studies. Consistent with data from previous studies, our results demonstrate a significantly altered microbial community structure with decreased heterogeneity in periodontal disease. Comparison with data from three previously reported studies revealed that subgingival microbiota clustered by study. However, differences between periodontal health and disease were larger than the technical variations across studies. Using a prediction score and applying five different distance metrics, we observed two predominant clusters. One cluster was driven by Fusobacterium and Porphyromonas and was associated with clinically apparent periodontitis, and the second cluster was dominated by Rothia and Streptococcus in the majority of healthy sites. The predicted functional capabilities of the periodontitis microbiome were significantly altered. Genes involved in bacterial motility, energy metabolism, and lipopolysaccharide biosynthesis were overrepresented in periodontal disease, whereas genes associated with transporters, the phosphotransferase system, transcription factors, amino acid biosynthesis, and glycolysis/gluconeogenesis were enriched in healthy controls. These results demonstrate significant alterations in microbial composition and function in periodontitis and suggest genes and metabolic pathways associated with periodontal disease. P eriodontal disease is a common disease affecting many adults in the United States. If left untreated, chronic periodontitis (CP) can lead to serious problems such as tooth loss. Indeed, periodontal disease is the number one cause of tooth loss in the United States, accounting for half of all tooth loss in U.S. adults (1). There is considerable evidence that the clinical impact of periodontal disease extends beyond the oral cavity (2). Strong associations have been found between periodontitis and a number of systemic conditions, including cardiovascular disease (3, 4), preterm delivery and low-birth-weight babies (5), diabetes mellitus (6-8), and rheumatoid arthritis (9-11).The activity of periodontal disease is determined by a complex interplay between the immune system and periodontal pathogens (12, 13). Alterations in subgingival microbiota have long been associated with the development and progression of periodontitis (14). In susceptible individuals, perturbations in...

Comparative In silico Analysis of Butyrate Production Pathways in Gut Commensals and Pathogens

“…Oral micriobiome of 25 healthy and 25 chronic periodontitis samples from American population (Kirst et al, 2015) (NCBI Bioproject ID PRJNA269205).…”

Signature of Microbial Dysbiosis in Periodontitis

“…The different microbiota clustered either by sampling site, such as the outgroups used as controls for this study (saliva samples in cluster 3 and dentine caries and vagina samples, which are both rich in Lactobacillus, in cluster 4), or by clinical status, such as subgingival samples (healthy samples in clusters 1 and 2 and CP samples in cluster 5). CP sites either can show greater microbial diversity and observed richness, compared with healthy subgingival sites (14,15), or can present no significant difference in microbial diversity, as reported for health versus periodontitis (16). Thus, the large number of samples surpasses the technical variations, at least at the genus level, with the primers used in the different studies, and the difference between periodontal health and disease is larger than the technical variations, as described by Kirst et al (16).…”

Characterizations of oral microbiota in elderly nursing home residents with diabetes

“…Recent studies have suggested that commensal bacterial species in the oral cavity may function as pathogens in a variety of systemic diseases, including aspiration pneumonia (3) and infective endocarditis (4), as well as having a relationship to pre-term low-weight births (5). Dysbiosis is defined as microbial imbalance, and the term oral dysbiosis has been applied to the association between oral bacterial composition and disorders such as periodontal disease (6) and obesity (7). It has become widely recognized that the gut microbiota is closely associated with health and disease in humans.…”

“…Similarly, the oral microbiota is also known to change in response to local and general conditions, and is considered to be an indicator of homeostatic deterioration (7,16,17). Although the association between oral and intestinal microbiota is unclear, recent studies have suggested that alterations in the microbial composition of dental plaque are associated with periodontal disease (6,18). In addition, a number of reports have suggested that periodontitis is linked to some systemic disorders, including diabetes mellitus (19,20).…”