Gabriel Baldanzi: Imprints on the gut microbiome: A study of sleep apnea, physical activity, and antibiotic use

Abstract

Growing evidence has highlighted the importance of the gut microbiome for human health. However, detailed investigations on how specific host factors influence the gut microbiome are lacking. The research in this thesis examined the relationship of obstructive sleep apnea (OSA), physical activity, and antibiotic use with the gut microbiome. The studies in this thesis used gut microbiome data from deep fecal shotgun metagenomics in large population-based cohorts.

Study I used the baseline data of 3,570 individuals aged 50-65 from the Swedish CArdioPulmonary bioImage Study (SCAPIS). OSA was assessed with respiratory polygraphy. We identified 128 microbiome species associated with the number of oxygen desaturation events per hour of sleep or the percentage of sleep time in hypoxia. For instance, more severe hypoxia during sleep was associated with higher abundance of Collinsela aerofaciens and Blautia obeum. Additionally, C. aerofaciens was also associated with increased systolic blood pressure.

Study II used baseline data from 8,416 SCAPIS participants who had valid accelerometer-derived physical activity data. The distribution of awake time in sedentary behavior or physical activity of different intensities was associated with the abundance of 651 gut microbiome species. For example, longer time in moderate-intensity physical activity and shorter time in sedentary behavior were associated with higher abundance of Prevotella copri and Faecalibacterium prausnitzii and lower abundance of Escherichia coli and [Ruminococcus] torques.

Study III investigated the association between antibiotic use in the past eight years and the gut microbiome in 15,131 participants from SCAPIS, the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research (SIMPLER), and the Malmö Offspring Study (MOS). Antibiotic use 4–8 years and 1–4 years earlier was associated with lower gut microbiome alpha diversity after adjustment for more recent use, sociodemographics, lifestyle, and comorbidities. Most of the species-level associations were found for the antibiotics clindamycin, fluoroquinolones, and flucloxacillin.

Study IV assessed the causal effect of physical activity on the gut microbiome using a two-sample Mendelian randomization (MR) analysis based on summary statistics from genome-wide association studies. We found evidence of a positive effect of moderate-to-vigorous intensity physical activity (MVPA) on gut microbiome alpha diversity. Using a multivariable MR analysis, we found that MVPA had a positive on alpha diversity independent of BMI, smoking, education, or liking of a low-calorie diet.

This thesis has applied diverse epidemiology and statistical methods to rigorously investigate host factor associations with the gut microbiome. Altogether, it underlines the tight host-microbiome connection through detailed analyses of OSA, physical activity, and antibiotic use with the gut microbiome.