Abstract
Sickle cell disease (SCD) is a chronic blood disorder that disrupts multiple organ systems and can lead to severe morbidity. Persistent and acute symptoms caused by immune system dysregulation in individuals with SCD could contribute to disease either directly or indirectly via dysbiosis of commensal microbes and increased susceptibility to infection. Here, we explored the nasal and oral microbiomes of children with SCD (cwSCD) to uncover potential dysbiotic associations with the blood disorder. Microbiota collected from nasal and oral swabs of 40 cwSCD were compared to eight healthy siblings using shotgun metagenomic sequencing. Commensal taxa were present at similar levels in the nasal and oral microbiome of both groups. However, the nasal microbiomes of cwSCD contained a higher prevalence of Pseudomonadota species, including pathobionts such as Yersinia enterocolitica and Klebsiella pneumoniae. Furthermore, the oral microbiome of cwSCD displayed lower α-diversity and fewer commensal and pathobiont species compared to the healthy siblings. Thus, subtle but notable shifts seem to exist in the nasal and oral microbiomes of cwSCD, suggesting an interaction between SCD and the microbiome that may influence health outcomes. IMPORTANCE: The oral and nasal cavities are susceptible to environmental exposures including pathogenic microbes. In individuals with systemic disorders, antibiotic exposure, changes to the immune system, or changes to organ function could influence the composition of the microbes at these sites and the overall health of individuals. Children with sickle cell disease (SCD) commonly experience respiratory infections, such as pneumonia or sinusitis, and may have increased susceptibility to infection because of disrupted microbiota at these body sites. We found that children with SCD (cwSCD) had more pathobiont bacteria in the nasal cavity and reduced bacterial diversity in the oral cavity compared to their healthy siblings. Defining when, why, and how these changes occur in cwSCD could help identify specific microbial signatures associated with susceptibility to infection or adverse outcomes, providing insights into personalized treatment strategies and preventive measures.