show Abstracthide AbstractWhile an increasing number of beneficial microbiome members is characterized for the human gut and vagina, beneficial microbes are underexplored for the human upper respiratory tract (URT). In this study, we demonstrate that taxa from the beneficial Lactobacillus genus might have a role as keystone species in the healthy URT. Several URT-specific Lactobacillus isolates were cultured, characterized, and further explored for their genetic and functional properties related to adaptation to the URT. Catalase genes were found in the identified Lactobacillus taxa, which is a unique feature within this mostly facultative anaerobic genus. Moreover, one of our isolated strains, Lactobacillus casei AMBR2, contained unique fimbriae enabling strong adherence to URT epithelium, inhibited the growth and virulence of several URT pathogens, and successfully colonized nasal epithelium of healthy volunteers. This study thus demonstrates that specific Lactobacillus taxa are adapted to the URT and could have a beneficial keystone function in this habitat.