0050 Impact of the Circadian System and Circadian Misalignment on Human Salivary Microbiota

Abstract

Introduction: Circadian rhythm disruption is prevalent in modern society, particularly in night shift workers. Circadian misalignment- the misalignment between the central circadian clock and behavioral/environmental cycles (including sleep/wake, fasting/ feeding, dark/light)-results in adverse metabolic effects. Potential underlying mechanisms for these adverse effects include alterations in orogastrointestinal microbiota. However, it remains to be established whether human salivary microbiota have circadian rhythmicity and whether circadian disruption impacts circadian rhythms, community structure, and composition of the microbiota. Method(s): Six healthy young individuals (27.3+/-2.3y; 2 females) underwent a 14-day stringently controlled circadian protocol, with a baseline 36-h constant routine paradigm (CR; circadian assessment; semi-recumbent posture, ~3 lux, and hourly isocaloric snacks), a Forced Desynchrony protocol (four 28-h "days"; ~3 lux; outside the range of circadian entrainment), to induce circadian misalignment, and a post-misalignment 44-h CR protocol. Microbiota assessments were performed on saliva samples during CR every 4h. Total DNA was extracted and processed using high-throughput 16S ribosomal RNA gene amplicon sequencing. Cosinor mixed models were applied to saliva microbiota relative abundance at the taxonomical levels of phylum and genus to identify circadian rhythms. Result(s): Our data indicate significant endogenous circadian rhythms in 1/6 of the dominant phyla (Proteobacteria; p=0.02), with a peak in the middle of the biological day (~12PM) and nadir in the biological night (~12AM). Significant circadian oscillations were observed for 1/4 of dominant genera within the Proteobacteria taxa (i.e., Neisseria; p=0.004). Following circadian misalignment, circadian rhythmicity for the Proteobacteria and their genera was abolished, while significant circadian rhythms arose for the phylum Bacteroidetes and their genera (i.e., Capnocytophaga; p=0.04), with a peak in the biological morning (~8AM) and nadir in the biological evening (~8PM). Importantly, we observed significant effects of circadian misalignment on overall/average relative abundance in 5/6 of dominant phyla and in 5/8 of the dominant genera. Conclusion(s): Our data show for the first time that human oral microbiota, particularly putative-proinflammatory taxa, exhibit circadian rhythmicity. Importantly, we show that circadian misalignment may result in changes in the relative abundance for a wide array of oral microbiota.