The term "bacterial dysbiosis" is being used quite extensively in metagenomic studies, however, the identification of harmful bacteria often fails due to large overlap between the bacterial species found in healthy volunteers and patients. We hypothesized that the pathogenic oral bacteria are individual-specific and they correlate with oxidative stress markers in saliva which reflect the inflammatory processes in the oral cavity. Temporally direct and lagged correlations between the markers and bacterial taxa were computed individually for 26 volunteers who provided saliva samples during one month (21.2 ± 2.7 samples/volunteer, 551 samples in total). The volunteers' microbiomes differed significantly by their composition and also by their degree of microbiome temporal variability and oxidative stress markers fluctuation. The results showed that each of the marker-taxa pairs can have negative correlations in some volunteers while positive in others. Streptococcus mutans, which used to be associated with caries before the metagenomics era, had the most prominent correlations with the oxidative stress markers, however, these correlations were not confirmed in all volunteers. The importance of longitudinal samples collections in correlation studies was underlined by simulation of single sample collections in 1000 different combinations which produced contradictory results. In conclusion, the distinct intra-individual correlation patterns suggest that different bacterial consortia might be involved in the oxidative stress induction in each human subject. In the future, decreasing cost of DNA sequencing will allow to analyze multiple samples from each patient, which might help to explore potential diagnostic applications and understand pathogenesis of microbiome-associated oral diseases.

CIBER in Epidemiology and Public Health Valencia Spain

Department of Genomics and Health Foundation for the Promotion of Health and Biomedical Research of Valencia Region Madrid Spain

Department of Genomics and Health Foundation for the Promotion of Health and Biomedical Research of Valencia Region UVEG Valencia Spain

Department of Genomics and Health Foundation for the Promotion of Health and Biomedical Research of Valencia Region UVEG Valencia Spain 4Australian Centre for Ecogenomics The University of Queensland St Lucia QLD Australia

Institute for Integrative Systems Biology UVEG Valencia Spain

Institute of Molecular Biomedicine Faculty of Medicine Comenius University Bratislava Slovakia

Institute of Molecular Biomedicine Faculty of Medicine Comenius University Bratislava Slovakia 6Institute of Physiology Academy of Sciences of the Czech Republic Praha Czech Republic

Institute of Molecular Biomedicine Faculty of Medicine Comenius University Bratislava Slovakia 7Institute of Physiology Faculty of Medicine Comenius University Bratislava Slovakia

School of Dentistry The University of Queensland Herston QLD Australia