Abstract

Weissella cibaria belongs to the Lactobacillaceae family and has been isolated from traditional fermented foods and saliva of children with good oral health. Previous investigations have shown that W. cibaria CMU (Chonnam Medical University) is expected to be safe based on results of in silico and in vitro analyses. However, there is a lack of studies assessing its safety in vivo. A toxicological safety evaluation of W. cibaria CMU was performed using an acute oral safety study in rats, a 14-day oral range finding study, a subsequent 13-week oral toxicity study in rats and a genetic toxicity battery (in vitro bacterial reverse mutation, in vitro chromosome aberration in Chinese Hamster Ovary cells and in vivo micronucleus study in mice). The results of the studies in rats showed that the acute lethal dose of W. cibaria CMU is > 5000 mg/kg body weight (bw)/day (1.8 × 109 CFU/kg bw/day) and the 14-day or 13-week no observed adverse effect level (NOAEL) is 5000 mg/kg bw/day (1.8 × 109 CFU/kg bw/day), the highest dose administered. W. cibaria CMU was non-mutagenic in the bacterial reverse mutation test and non-clastogenic or aneugenic in vitro and in vivo. In conclusion, the toxicological studies performed demonstrated W. cibaria CMU to be a safe strain to consume. This study is the first study examining the potential of a W. cibaria strain to cause genetic toxicity and subchronic toxicity in rats according to the Organization for Economic Cooperation and Development guidelines.

Highlights

  • The Weissella genus includes a number of heterofermentative Leuconostoc-like lactic acid bacteria that are generally isolated from fermented foods [1, 2]

  • The highest dose to be used in the 13-week study was chosen as 5000 mg/kg bw/day (1.8 × ­109 CFU/kg bw/day) based on the results

  • Results of previous studies indicate that the strain is susceptible to common antibiotics, with the possible exception of kanamycin and vancomycin, but does not transfer resistance of these antibiotics to other bacteria [8]

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Summary

Introduction

The Weissella genus includes a number of heterofermentative Leuconostoc-like lactic acid bacteria that are generally isolated from fermented foods [1, 2]. Weissella cibaria is described as a short, rod-shaped, Gram-positive, non-sporeforming, nonmotile, heterofermentative, and catalase-negative lactic acid bacterium [3]. W. cibaria CMU (Chonnam Medical University) has been isolated from saliva samples of children who had little supragingival plaque and no oral diseases including dental caries [4]. Strain CMU has been identified as W. cibaria based on whole genome sequence analysis and phylogenetic homology [3,4,5,6]. W. cibaria is registered as a safe raw material by the Korea Food and Drug Administration (KFDA) and is found in several commercialized oral care probiotics in Korea [7, 8]. W. cibaria CMU exhibits several properties for maintenance of oral health, including inhibition of biofilm formation by Streptococcus mutans, antibacterial activity against cariogens (S. mutans and Streptococcus sobrinus)

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