Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients

Probiotics are routinely administered to hospitalized patients for a myriad of potential indications(1) but have been associated with adverse effects that may outweigh their potential benefits(2–7). Particularly alarming is the possibility that probiotic strains can cause bacteremia(8,9), yet direct evidence for an ancestral link between blood isolates and administered probiotics is lacking. Here, focusing on intensive care unit (ICU) patients, we find markedly increased risk of Lactobacillus bacteremia among patients treated with probiotics, and we provide genomics data that support direct clonal transmission of probiotics to the bloodstream. Whole-genome based phylogeny showed that Lactobacilli isolated from the blood of these treated patients were phylogenetically inseparable from Lactobacilli isolated from the associated probiotic product. Indeed, the minute genetic diversity among the blood isolates mostly mirrored preexisting genetic heterogeneity found in the probiotic product. Some blood isolates also had de novo mutations, including a non-synonymous SNP conferring antibiotic resistance in one patient. Our findings support that probiotic strains can directly cause bacteremia and adaptively evolve within ICU patients.