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Klebsiella ARO112 promotes microbiota recovery, pathobiont clearance and prevents
inflammation in IBD mice
#MMPMID41381568
Cabral V
; Oliveira RA
; Correia MB
; Pedro MF
; García-Garcerá M
; Ubeda C
; Xavier KB
Nat Commun
2025[Dec]; 16
(1
): 10911
PMID41381568
show ga
Precise microbiota modulation towards improving immune function and metabolic
homeostasis is a major goal in clinical research. It is also critical for
reducing pathogen invasion or pathobiont expansion, contributors to epidemic
Inflammatory Bowel Diseases (IBD), where recurrent antibiotic treatments often
exacerbate microbiota imbalances. Within the thousands of strains of a natural
gut microbiota, we previously identified a specific Klebsiella strain, ARO112,
capable of promoting resistance to, and clearance of, pathogenic
Enterobacteriaceae. Here, we assess its therapeutic potential using a
comprehensive genomic and phenotypic analysis and experiments in mouse models of
IBD. We demonstrate that ARO112 not only exhibits a safety profile comparable to
the widely used probiotic Escherichia coli Nissle 1917, but also has a reduced
capacity to acquire antibiotic resistance, via horizontal gene transfer, and to
capture iron, thereby bypassing major concerns associated with pathogenic
Enterobacteriaceae strains. In antibiotic-treated, genetically predisposed IBD
mice, ARO112 accelerates pathobiont clearance, promotes the recovery of
microbiota diversity, elevates intestinal butyrate concentration, and prevents
mild inflammation. Moreover, even in the absence of pathogen infection, ARO112
prevents severe inflammation-driven pathology in a chemically-induced colitis
model. Our findings highlight ARO112 as a potential biotherapeutic agent that
disrupts inflammation-treatment-infection cycles characteristic of chronic gut
inflammatory diseases.
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