Gut protectiveKlebsiellaspecies promotes microbiota recovery and pathobiont clearance while preventing inflammation

Abstract

AbstractThe microbiota inhabiting the mammalian gut serves as a protective barrier against pathogen invasion through a mechanism known as colonization resistance. Antibiotic treatments can inadvertently disturb the gut microbiota, compromising colonization resistance and increasing host’s susceptible to infections. Non-pneumoniae Klebsiellaspp. members of the gut microbiota play a crucial role in colonization resistance and clearance from the gut of pathogenicEnterobacteriaceaefollowing antibiotic-induced perturbations. Specifically,Klebsiellastrain ARO112 a gut microbiota isolate, can effectively resist and clearEscherichia colicolonization after antibiotic-induced dysbiosis.We assessed the potential ofKlebsiellasp ARO112 to promote clearance ofEnterobacteriaceaepathobiont Adherent-InvasiveE. coli(AIEC) in an Inflammatory Bowel Disease (IBD) mouse model susceptible to inflammatory episodes. In antibiotic-treated IBD-predisposed mice infected with the AIEC,Klebsiellasp. ARO112 promoted a faster recovery of gut microbiota members potentially involved in butyrate production and accelerated pathobiont clearance. Functionally, ARO112-driven microbiota recovery promoted higher butyrate levels and prevented intestinal inflammation compared to untreated animals. Conversely, treatment with the well-known probioticE. coliNissle 1917 enhanced AIEC colonization and inflammation. Furthermore, we assessed the safety of ARO112 as a potential next-generation probiotic; phenotypic comparison of ARO112 against closely relatedEnterobacteriaceaerevealed its lower pathogenic potential, including being more recalcitrant to antibiotic resistance acquisition.Overall, our results showing thatKlebsiellasp. ARO112 can resolve infections while contributing to the promotion of intestinal health, underscore its potential as a biotherapy agent that can disrupt inflammation-treatment-infection cycles. This potential extends beyond IBD patients, encompassing individuals with other inflammatory-based conditions related to microbiota imbalances.