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Nat Med. 2019 Nov;25(11):1728-1732. doi: 10.1038/s41591-019-0626-9. Epub 2019 Nov 7.

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

Author information

1
Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
2
Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
3
Harvard Medical School, Boston, MA, USA.
4
Novant Health Eastover Pediatrics, Charlotte, NC, USA.
5
Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
6
Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.
7
Walter Reed Army Institute of Research, Silver Spring, MD, USA.
8
Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
9
Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA. thomas.sandora@childrens.harvard.edu.
10
Harvard Medical School, Boston, MA, USA. thomas.sandora@childrens.harvard.edu.
11
Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel. rkishony@technion.ac.il.
12
Department of Computer Science, Technion-Israel Institute of Technology, Haifa, Israel. rkishony@technion.ac.il.
13
Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA. gregory.priebe@childrens.harvard.edu.
14
Harvard Medical School, Boston, MA, USA. gregory.priebe@childrens.harvard.edu.
15
Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA. gregory.priebe@childrens.harvard.edu.

Abstract

Probiotics are routinely administered to hospitalized patients for many potential indications1 but have been associated with adverse effects that may outweigh their potential benefits2-7. It is particularly alarming that probiotic strains can cause bacteremia8,9, yet direct evidence for an ancestral link between blood isolates and administered probiotics is lacking. Here we report a markedly higher risk of Lactobacillus bacteremia for intensive care unit (ICU) patients treated with probiotics compared to those not treated, and provide genomics data that support the idea of direct clonal transmission of probiotics to the bloodstream. Whole-genome-based phylogeny showed that Lactobacilli isolated from treated patients' blood were phylogenetically inseparable from Lactobacilli isolated from the associated probiotic product. Indeed, the minute genetic diversity among the blood isolates mostly mirrored pre-existing genetic heterogeneity found in the probiotic product. Some blood isolates also contained 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.

PMID:
31700189
DOI:
10.1038/s41591-019-0626-9

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