Helicobacter pylori Infection in Infant Rhesus Macaque Monkeys is Associated with an Altered Lung and Oral Microbiome.

BACKGROUND

It is estimated that more than half of the world population has been infected with . Most newly acquired infections occur in children before 10 years of age. We hypothesized that early life infection could influence the composition of the microbiome at mucosal sites distant to the stomach. To test this hypothesis, we utilized the infant rhesus macaque monkey as an animal model of natural colonization to determine the impact of infection on the lung and oral microbiome during a window of postnatal development.

RESULTS

From a cohort of 4-7-month-old monkeys, gastric biopsy cultures identified 44% of animals infected by . 16S ribosomal RNA gene sequencing of lung washes and buccal swabs from animals showed distinct profiles for the lung and oral microbiome, independent of infection. In relative order of abundance, the lung microbiome was dominated by the phyla Proteobacteria, Firmicutes, Bacteroidota, Fusobacteriota, Campilobacterota and Actinobacteriota while the oral microbiome was dominated by Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota. Relative to the oral cavity, the lung was composed of more genera and species that significantly differed by status, with a total of 6 genera and species that were increased in negative infant monkey lungs. Lung, but not plasma IL-8 concentration was also associated with gastric load and lung microbial composition.

CONCLUSIONS

We found the infant rhesus macaque monkey lung harbors a microbiome signature that is distinct from that of the oral cavity during postnatal development. Gastric colonization and IL-8 protein were linked to the composition of microbial communities in the lung and oral cavity. Collectively, these findings provide insight into how infection might contribute to the gut-lung axis during early childhood and modulate future respiratory health.