Long-term dynamics of the human oral microbiome during clinical disease progression

Abstract

Background: Oral microbiome dysbiosis is linked to overt inflammation of tooth-supporting tissues, leading to periodontitis, an oral condition that can cause tooth and bone loss. Microbiome dysbiosis has been described as a disruption in the symbiotic microbiota composition’s stability that could adversely affect the host’s health status. However, the precise microbiome dynamics that lead to dysbiosis and the progression of the disease are largely unknown. The objective of our study was to investigate the long-term dynamics of periodontitis progression and its connection to dysbiosis. Results: We studied three different teeth groups: sites that showed disease progression, sites that remained stable during the study, and sites that exhibited a cyclic deepening followed by spontaneous recovery. Time-series analysis revealed that communities followed a characteristic succession of bacteria clusters. Stable and fluctuating sites showed high asynchrony in the communities (i.e., different species responding dissimilarly through time) and a reordering of the communities where directional changes dominated (i.e., sample distance increases over time) in the stable sites but not in the fluctuating sites. Progressing sites exhibited low asynchrony and convergence (i.e., samples distance decreases over time). Moreover, new species were more likely to be recruited in stable samples if a close relative was not recruited previously. In contrast, progressing and fluctuating sites followed a neutral recruitment model, indicating that competition between closely related species is a significant component of species-species interactions in stable samples. Finally, periodontal treatment did not select similar communities but stabilized α-diversity, centered the abundance of different clusters to the mean, and increased community rearrangement. Conclusions: Here, we show that ecological principles can define dysbiosis and explain the evolution and outcomes of specific microbial communities of the oral microbiome in periodontitis progression. All sites showed an ecological succession in community composition. Stable sites were characterized by high asynchrony, a reordering of the communities where directional changes dominated, and new species were more likely to be recruited if a close relative was not recruited previously. Progressing sites were characterized by low asynchrony, community convergence, and a neutral model of recruitment. Finally, fluctuating sites were characterized by high asynchrony, community convergence, and a neutral recruitment model.