Toxicological and safety evaluations of W e issella cibaria strain CMU in animal toxicity and genotoxicity

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.

Keywords: Acute; Clastogenicity; Mutagenicity; NOAEL; Rat; Safety; Subchronic; Weissella cibaria.

Fig. 1

Body weights of male rats in 13-week study of W. cibaria CMU. Individual animal weight was recorded at acquisition, grouping, at the before administration, once a week during the study and before necropsy. Body weights of males in the 2500 and 5000 mg/kg bw/day groups were less than controls at week 4, all groups of treated males exhibited lower body weights than controls from weeks 5–8, and males in the 2500 mg/kg bw/day also had lower body weights than controls at week 12. ^*Significant difference compared with control group, p < 0.05

Fig. 2

Body weights of female rats in 13-week study of W. cibaria CMU. Individual animal weight was recorded at acquisition, grouping, at the before administration, once a week during the study and before necropsy. There was no effect of the test material on female body weight