Metabiosis underlies a microbiota permissive to Pseudomonadota and increases the risk of gut-borne bloodstream infection

The gut microbiota contains trillions of bacteria essential to health, but also harbors potential pathogens. The phylum Pseudomonadota, which includes Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, typically composes <1% of the microbiota but causes disproportionate numbers of gut-borne bloodstream infections. Identifying the ecological dependencies that enable Pseudomonadota to cause gut-borne disease is important for human health. Here, we studied microbiota dynamics in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) to find that microbiota compositions permissive to Pseudomonadota had, following antibiotic prophylaxis, high levels of Bacteroides--a major reservoir of polysaccharide utilization loci (PULs). We tested the causality of this clinical association in a mouse co-colonization model and discovered that Bacteroides fragilis promotes Pseudomonas gut colonization and survival to ciprofloxacin, a drug commonly used as prophylactic in allo-HCT. In vitro experiments revealed a general mechanism by which diverse Pseudomonadota species depend on Bacteroides polysaccharide breakdown to grow better, form more biofilm, and survive ciprofloxacin treatment under anaerobic conditions, a type of ecological dependency termed metabiosis. Guided by this insight, we used metagenomics to identify the PUL-encoded functions underlying the metabiotic potential of a patients microbiota and establish a link to gut-derived Gram-negative bacteremia in allo-HCT. Together, our findings translate mechanistically based microbiome ecology into a clinically actionable framework for early risk stratification and intervention.