Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients
Open accessAbstract
Probiotics are routinely administered to hospitalized patients for many potential indications 1 but have been associated with adverse effects that may outweigh their potential benefits 2-7. It is particularly alarming that probiotic strains can cause bacteremia 8,9, 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.
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In non-ICU patients not prescribed probiotics, the incidence of LB was 10/93,000 (0.0001%).
“The incidence of LB in non-ICU patients not prescribed probiotics was even lower (10/93,000; 0.0001%) and was caused by a variety of lactobacilli (Lcb. rhamnosus, Lpb. plantarum, Lcb. Casei, or L. gasseri), but once again, the strains were not reported.”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [47]
The epidemiological results (passage [1]) report ten cases among approximately 93,000 non-ICU patients, none of whom were receiving a probiotic at the time of bacteremia. The stated percentage is incorrect: 10/93,000 is approximately 0.01%, not 0.0001%. (LLM, conf=0.94)
Experimental — accuracy not yet measuredIn ICU patients not taking probiotics, only two (0.009%) cases of LB were detected among 21,652 patients.
“One study reviewed cases reported over 5.5 years at a hospital in Boston, Massachusetts, and found of 21,652 patients admitted to their ICU who were not taking any probiotics, only two (0.009%) cases of LB were detected, which were caused by either L. acidophilus or Lpb. plantarum, but the specific strain was not reported [47].”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [47]
The paper reports two cases of Lactobacillus bacteremia (0.009%) among 21,652 ICU patients who did not receive an LGG-containing probiotic. It does not define that entire group as taking no probiotics: the Patient inclusion criteria and clinical data section says 645 ICU patients received probiotics, but only 522 received one containing LGG. The case count and rate match, but the claim broadens the comparison group incorrectly. (LLM, conf=0.91)
Experimental — accuracy not yet measuredOur review revealed 49 case reports of LB without any history of probiotic use.
“Our review also revealed 49 case reports of LB without any history of probiotic use (Table 1) [24,26,27,33,35,45,46,47,48,49,50,51].”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [47]
The Patient inclusion criteria and clinical data section (page unavailable) reports 12 cases of Lactobacillus bacteremia in patients not receiving probiotics, so this paper could contribute cases to the citing review. It does not establish the review’s total of 49 case reports or rule out any prior history of probiotic use. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOur review of the literature (from 1980 to 2023) found 23 cases where the blood isolate from a bacteremic patient was identical to the probiotic strain the patient had been taking.
“Our review of the literature (from 1980 to 2023) found 23 cases where the blood isolate from a bacteremic patient was identical to the probiotic strain the patient had been taking.”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [47]
The genomic analysis reports six probiotic-treated patients whose blood isolates were phylogenetically inseparable from isolates in the probiotic product. It does not report a literature review from 1980 to 2023 or a finding of 23 such cases; the paper was published in 2019. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBlood isolate mutations did not appear in the probiotic isolates, suggesting de novo evolution within the patient.
“In addition, they identified blood isolate mutations that did not appear in the probiotic isolates, suggesting de novo evolution within the patient.”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [47]
Yelin et al. reported that 6 of 522 (1.1%) pediatric patients admitted to an ICU and receiving the probiotic Lcb. rhamnosus strain GG developed Lactobacillus bacteremia compared to only 2 of the 21,652 (0.009%) patients who did not receive Lcb. rhamnosus GG.
“Yelin et al. reported that 6 of 522 (1.1%) pediatric patients admitted to an ICU at a Boston Massachusetts hospital and receiving the probiotic Lcb. rhamnosus strain GG developed Lactobacillus bacteremia compared to only 2 of the 21,652 (0.009%) patients who did not receive Lcb. rhamnosus GG [47].”
From Lactobacillus Bacteremia and Probiotics: A Review (2023) · cites this paper as [47]
Among critically ill patients, commercial probiotics can even lead to bacteremia.
“In critically ill patients, commercial probiotic use may even cause bacteremia (145).”
From The microbiome and human cancer (2021) · cites this paper as [145]
Some studies have demonstrated an association with increased risk of bacteremia in intensive care units or tumor growth following probiotic supplementation.
“Safety needs to be primarily considered as some studies have demonstrated an association with an increased risk of bacteremia in intensive care units (Yelin et al., 2019) or tumor growth (Arthur et al., 2013) following probiotic supplementation.”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Yelin et al., 2019
A small but significant increase in Lactobacillus bacteremia was observed in intensive care unit patients receiving probiotics in a Boston hospital, albeit this was not linked directly to colonization of the probiotic.
“This last example was observed in a small but significant increase in Lactobacillus bacteremia in intensive care unit patients receiving probiotics in a Boston hospital, albeit this was not linked directly to colonization of the probiotic.92”
From Emerging issues in probiotic safety: 2023 perspectives (2023) · cites this paper as [92]
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- Authors
- Yelin, I., Flett, K. B., Merakou, C., Mehrotra, P., Stam, J., Snesrud, E., Hinkle, M., Lesho, E., McGann, P., McAdam, A. J., Sandora, T. J., Kishony, R., & Priebe, G. P.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Boston Children's Hospital (US)
- Walter Reed Army Institute of Research (US)
- Corresponding author
- Sandora, Thomas J.
- Kishony, Roy
- Priebe, Gregory P.
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-11
- Volume
- 25
- Issue
- 11
- Pages
- 1728-1732
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6980696
- OpenAlex
- W2987760949
- Cited by
- 315
- References
- 42
- Citations by year
- 2026: 43 · 2025: 55 · 2024: 36 · 2023: 41 · 2022: 53 · 2021: 41 · 2020: 39 · 2019: 6
- FWCI
- 27.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Boston Children's Hospital
- National Institutes of Health (281891, GM081617)
- Centers for Disease Control and Prevention
- National Institute of General Medical Sciences (R01GM081617)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- probiotics, bacteremia, Lactobacillus, intensive care unit patients, clonal transmission, whole-genome phylogeny, bloodstream infection, antibiotic resistance, de novo mutations
- MeSH terms
- Whole Genome Sequencing, Diarrhea, Humans, Intensive Care Units, Lactobacillus, Mutation, Phylogeny, Genetic Variation, Bacteremia, Genome, Bacterial, Probiotics, Polymorphism, Single Nucleotide, Genomics, Drug Resistance, Bacterial
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