Evaluation of the effect of the probiotic Klebsiella ARO112 in the microbiome of IBD mice

The mammalian gut microbiota plays a role in host physiology, influencing immune function, metabolic homeostasis, disease susceptibility, and resistance to pathogen invasion and pathobiont expansion. Non-pneumoniae Klebsiella gut microbiota members play a crucial role in promoting resistance to, and clearance of, pathogenic Enterobacteriaceae following antibiotic exposure. Here, we assessed the therapeutic potential of Klebsiella sp. ARO112 as a next-generation probiotic in mouse models of Inflammatory Bowel Disease (IBD). We demonstrate that ARO112 exhibits a safety profile comparable to the widely used probiotic E. coli Nissle 1917, including a significantly reduced capacity to acquire antibiotic resistance genes via horizontal gene transfer, a major concern among Enterobacteriaceae. In antibiotic-treated, genetically predisposed IBD mice, ARO112 accelerated pathobiont clearance, promoted microbiota recovery, elevated intestinal butyrate levels, and prevented mild inflammation. Moreover, in a chemically-induced colitis model, ARO112 prevented severe inflammation-driven pathology even without pathogen infection. Our findings highlight ARO112's potential as a biotherapeutic agent disrupting inflammation-treatment-infection cycles characteristic of IBD and related conditions.