ena-STUDY-NATIONAL HEART AND LUNG INSTITUTE, IMPERIAL COLLEGE LONDON-11-06-2021-15:36:33:022-854
Immune dysregulation associated with respiratory illness in elite athletes
ABSTRACTRationale: Elite athletes are susceptible to respiratory tract infection (RTI) leading to significant training and in-competition time loss.Objective: This prospective study aimed to understand RTI susceptibility in elite athletes through systematic clinical and immune phenotyping in a cohort of 121 elite Olympic athletes.Methods/measurements: We performed comprehensive clinical and respiratory function phenotyping to identify athletes highly susceptible and non-susceptible to RTI. Baseline T and B cell peripheral lymphotype phenotyping was performed by flow cytometry with findings validated by mass cytometry in repeat samples. Viral immune response was analysed through peripheral blood mononuclear cell (PBMC) stimulation assays. Further immune phenotyping was performed through 16s rRNA microbial sequencing of oropharyngeal swabs and global untargeted plasma metabolomic profiling. Findings were compared to non-athlete healthy controls.Main Results: Clinical phenotyping revealed 23 athletes as highly susceptible to RTI with 23 athletes non-susceptible. Immune phenotyping revealed that highly susceptible athletes had a significantly reduced peripheral memory T regulatory cell compartment compared to non-susceptible athletes and healthy controls. The PBMC immune response to viral ligands in highly susceptible athletes also revealed a pro-inflammatory skewed T helper 2 response. Analysis of the oropharyngeal microbiome revealed reduced bacterial biomass in elite athletes compared to healthy controls. Metabolomic profiling revealed significant differences in sphingolipid pathway metabolites between RTI highly susceptible, non-susceptible athletes and healthy controls.Conclusion: in this study we highlight a RTI-susceptible elite athlete endotype and show the presence of a persistent reduction in circulating memory T regulatory cells with further evidence of bacterial dysbiosis and metabolic dysregulation of the sphingolipid pathway.
ABSTRACTRationale: Elite athletes are susceptible to respiratory tract infection (RTI) leading to significant training and in-competition time loss.Objective: This prospective study aimed to understand RTI susceptibility in elite athletes through systematic clinical and immune phenotyping in a cohort of 121 elite Olympic athletes.Methods/measurements: We performed comprehensive clinical and respiratory function phenotyping to identify athletes highly susceptible and non-susceptible to RTI. Baseline T and B cell peripheral lymphotype phenotyping was performed by flow cytometry with findings validated by mass cytometry in repeat samples. Viral immune response was analysed through peripheral blood mononuclear cell (PBMC) stimulation assays. Further immune phenotyping was performed through 16s rRNA microbial sequencing of oropharyngeal swabs and global untargeted plasma metabolomic profiling. Findings were compared to non-athlete healthy controls.Main Results: Clinical phenotyping revealed 23 athletes as highly susceptible to RTI with 23 athletes non-susceptible. Immune phenotyping revealed that highly susceptible athletes had a significantly reduced peripheral memory T regulatory cell compartment compared to non-susceptible athletes and healthy controls. The PBMC immune response to viral ligands in highly susceptible athletes also revealed a pro-inflammatory skewed T helper 2 response. Analysis of the oropharyngeal microbiome revealed reduced bacterial biomass in elite athletes compared to healthy controls. Metabolomic profiling revealed significant differences in sphingolipid pathway metabolites between RTI highly susceptible, non-susceptible athletes and healthy controls.Conclusion: in this study we highlight a RTI-susceptible elite athlete endotype and show the presence of a persistent reduction in circulating memory T regulatory cells with further evidence of bacterial dysbiosis and metabolic dysregulation of the sphingolipid pathway.