Proof‐of‐principle demonstration of endogenous circadian system and circadian misalignment effects on human oral microbiota

Abstract

Circadian misalignment—the misalignment between the central circadian “clock” and behavioral and environmental cycles (including sleep/wake, fasting/eating, dark/light)—results in adverse cardiovascular and metabolic effects. Potential underlying mechanisms for these adverse effects include alterations in the orogastrointestinal microbiota. However, it remains unknown whether human oral microbiota has endogenous circadian rhythms (i.e., independent of sleep/wake, fasting/eating, and dark/light cycles) and whether circadian misalignment influences oral microbiota community composition. Healthy young individuals [27.3 ± 2.3 years (18–35 years), 4 men and 2 women, body‐mass index range: 18–28 kg/m2] were enrolled in a stringently controlled 14‐day circadian laboratory protocol. This included a 32‐h constant routine (CR) protocol (endogenous circadian baseline assessment), a forced desynchrony protocol with four 28‐h “days” under ~3 lx to induce circadian misalignment, and a post‐misalignment 40‐h CR protocol. Microbiota assessments were performed on saliva samples collected every 4 h throughout both CR protocols. Total DNA was extracted and processed using high‐throughput 16S ribosomal RNA gene amplicon sequencing. The relative abundance of specific oral microbiota populations, i.e., one of the five dominant phyla, and three of the fourteen dominant genera, exhibited significant endogenous circadian rhythms. Importantly, circadian misalignment dramatically altered the oral microbiota landscape, such that four of the five dominant phyla and eight of the fourteen dominant genera exhibited significant circadian misalignment effects. Moreover, circadian misalignment significantly affected the metagenome functional content of oral microbiota (inferred gene content analysis), as indicated by changes in specific functional pathways associated with metabolic control and immunity. Collectively, our proof‐of‐concept study provides evidence for endogenous circadian rhythms in human oral microbiota and show that even relatively short‐term experimental circadian misalignment can dramatically affect microbiota community composition and functional pathways involved in metabolism and immune function. These proof‐of‐principle findings have translational relevance to individuals typically exposed to circadian misalignment, including night shift workers and frequent flyers.

Gut Microbiota Dysbiosis and Sleep Disorders: Culprit in Cardiovascular Diseases

“…Another very recent study by Chellappa, S.L. et al [ 31 ] focused on the endogenous circadian system and circadian misalignment effects on human microbiota. They structured a 14-day stringently controlled circadian laboratory protocol in six healthy humans analyzing GM oral changes from their saliva samples.…”

Daytime eating prevents mood vulnerability in night work

“…Preclinical work shows that circadian disruption perturbs microbiota communities ( 16 ). Moreover, circadian misalignment in humans can alter microbiota composition, possibly with a shift toward proinflammatory taxa and decreased abundance in microbiota-mediated functional pathways, including tryptophan biosynthesis essential for serotonin production ( 17 ). Thus, circadian misalignment may adversely affect the microbiota with ramifications for mental health.…”

Timing Matters: The Interplay between Early Mealtime, Circadian Rhythms, Gene Expression, Circadian Hormones, and Metabolism—A Narrative Review

“…Consequently, the timing of feeding serves as a connection between the circadian patterns in host behavior and the diurnal variations in the composition and role of the microbiota [ 191 , 202 ]. Furthermore, circadian misalignment in humans can modify the composition of the microbiota, potentially leading to an increase in proinflammatory taxa and a decrease in functional pathways mediated by the microbiota [ 203 ]. One of the affected pathways is the biosynthesis of tryptophan, which is crucial for serotonin production [ 203 ].…”

“…Furthermore, circadian misalignment in humans can modify the composition of the microbiota, potentially leading to an increase in proinflammatory taxa and a decrease in functional pathways mediated by the microbiota [ 203 ]. One of the affected pathways is the biosynthesis of tryptophan, which is crucial for serotonin production [ 203 ].…”