Work

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

Year: 2026

Type: preprint

Abstract: 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 patient’s 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.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.64898/2026.04.20.716137