Exploring the Interplay Between Fatigue and the Oral Microbiome: A Longitudinal Approach

Fatigue is a pervasive burden for emerging medical professionals, often impacted by stress and lifestyle factors, yet insufficiently explained by these aspects alone. Considering the profound immediate and long-term consequences for physician well-being and patient care, exploring the interplay between biological factors, such as the oral microbiome and fatigue, emerges as a critical area of investigation. This exploratory longitudinal study investigates the relationship between oral microbiome diversity and fatigue in first-year medical students across four timepoints, where they provided buccal swabs and completed lifestyle and standardized stress, sleep, and fatigue assessments (PSQI, FAS, PSS). Microbiome analysis was performed using 16S rRNA sequencing and QIIME2-based bioinformatics to identify genus-level profiles and core microbiome composition. Forty-five healthy participants were assessed. Significant increases in fatigue and fluctuations in oral microbiome diversity were observed, with alpha diversity peaking mid-year before declining. Illness frequency and antibiotic use also rose, potentially influencing microbial shifts. These fluctuations may be indicative of an adaptation process where oral microbial diversity adjusts to changes in the subject's environment, which in this case is entering medical school. Despite no clear clustering in biodiversity metrics, associations between fatigue and microbiome richness were noted, suggesting that physiologic fatigue and environmental stressors may contribute to microbial variability. Limitations of the study include a small sample size, attrition, and representativeness of the study population. This study presents a longitudinal baseline that may serve as a reference for future investigations. These findings may support the development of targeted interventions designed to modulate microbial composition as a novel approach to alleviating fatigue.