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bioRxiv · 10.64898/2026.04.20.716137

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

Wucher, B. R.·Pardo-De la Hoz, C. J.·Stamper, I.·Sharma, S.·Kaune, D.·Bendale, P.·Peled, J.·Xavier, J.
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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 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.

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Wucher, B. R., Pardo-De la Hoz, C. J., Stamper, I., Sharma, S., Kaune, D., Bendale, P., Peled, J., Xavier, J.. 2026-04-21. Metabiosis underlies a microbiota permissive to Pseudomonadota and increases the risk of gut-borne bloodstream infection. https://doi.org/10.64898/2026.04.20.716137

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