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Assessment of the Safety of Lactobacillus casei IMV B-7280 Probiotic Strain on a Mouse Model

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Abstract

Probiotics, in particular Lactobacillus (lactic acid bacteria, LAB) strains, are widely used in clinical practice. Despite that these probiotics have GRAS (generally regarded as safe) and qualified presumption of safety (QPS) statuses, the safety of particular strains still needs to be thoroughly studied. The aim of the study was to evaluate the safety of Lact. casei IMV B-7280 strain by investigating toxicity and the effects on gut microbiota in experimental animal model. Male BALB/c mice (7–8 weeks, weight 20–24 g) were treated with amounts of Lact. casei IMV B-7280 strain: 5 × 106, 5 × 108, or 5 × 109 CFU/animal once per day during 7 days, or in the amount of 1 × 1010 CFU/animal once per day during 3 days (most of the proposed probiotic doses for humans—from 108 to 109 CFU) and monitored during 14 days. Blood tests and serum biochemistry were conducted; the cecal content from mice of the experimental and control groups were freshly collected and analyzed. At the end of the experiments (15th day), the presence of LAB in the heart, liver, kidney, and mesenteric lymph nodes and peripheral blood was determined; histology of the brain, liver, heart, fragments of the small and large intestine, and mesenteric lymph nodes was conducted. Survival rate of BALB/c mice treated with Lact. casei IMV B-7280 strain in different concentrations in toxicity experiments during 14 days was 100%. We observed no signs of toxicity as changes in gait, lethargy, sleep, somatomotor activity as well as changes in fur, eyes, skin and mucous membranes, tremors, behavior pattern, convulsions, salivation, diarrhea, and local injuries in mice from all experimental groups. After administration of probiotic strain, the number of opportunistic bacteria in cecal contents, such as Staphylococcus spp., Candida spp., Pseudomonas spp., and total aerobic and optionally anaerobic bacteria decreased compared to controls; the population of beneficial bacteria such as lactobacilli increased in cecal contents of these mice. LAB were not detected in the peripheral blood, heart, liver, kidneys, and mesenteric lymph nodes after administration of this strain to intact mice. Lact. casei IMV B-7280 strain is safe at dose up to 1010 CFU/animal during 3- and 7-day oral administration to mice and has a positive effect on the gut microbiota composition; it could be potentially considered as safe probiotic for humans.

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Data are available on reasonable request to the authors.

Abbreviations

LAB :

Lactobacillus (lactic acid bacteria)

QPS:

Qualified presumption of safety status

GRAS:

(Generally regarded as safe) status

CFU:

Colony forming units

Lg:

Logarithm

WBC:

Leukocytes

LY:

Lymphocytes

MO:

Monocytes

GR:

Granulocytes

RBC:

Erythrocytes

Hgb:

Hemoglobin

HCT:

Hematocrit

MCV:

Average size of red blood cells

MCH:

Hemoglobin content of red blood cells

MCHC:

Mean hemoglobin content of red blood cells, not whole blood

RDW:

Red cell distribution width

PLT:

Absolute platelet content

PTC:

Plasma thromboplastin component

MPV:

Mean platelet volume

PDW:

Platelet distribution width

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Acknowledgements

The research work was partially done as a part of the project titled «Development of probiotics for the prevention and treatment of infectious-inflammatory diseases» (DZ/48-2018) that was funded by the Ministry of Education and Science of Ukraine. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Zabolotny Institute of microbiology and virology, National Academy of Sciences of Ukraine, 154, Akad. Zabolotny str, Kyiv, 03143, Ukraine

    Lazarenko L.M., Babenko L.P., Demchenko O.M., Bubnov R.V. & Spivak M.Ya.

  2. Bogomolets National Medical University, 13, T. Shevchenko blvd, Kyiv, 01601, Ukraine

    Gichka S.G.

  3. RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, 45, Vasylkivska str, Kyiv, 03022, Ukraine

    Sakhno L.O.

  4. Pure Research Products, LLC, 6107 Chelsea Manor Court, Boulder, Colorado, 80301, USA

    Sichel L.M.

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L.M., L., L.P., B., S.G., G. et al. Assessment of the Safety of Lactobacillus casei IMV B-7280 Probiotic Strain on a Mouse Model . Probiotics & Antimicro. Prot. 13, 1644–1657 (2021). https://doi.org/10.1007/s12602-021-09789-1

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