Single and repeated-dose toxicity studies by intravaginal administration of Lactobacillus plantarum ATG-K2 powder in female rats.

Abstract

Bacterial vaginosis (BV) is a microbial dysbiosis that shifts the paradigms of vaginal flora from lactobacilli to opportunistic pathogens. Globally, BV is treated with antibiotic therapy and recurrence rates are > 70% occurring within 6 months due to antibiotic resistance against pathogenic bacteria. An incorporation of lactobacilli orally or intravaginally for the recolonization of healthy microbes in vagina is the suggested course of treatment. Although Lactobacilli are suggested as a novel therapeutic for women's BV, evaluation of safety and toxicity have not been well understood previously. Therefore, in this study, we aimed to evaluate the safety profile of Lactobacillus plantarum ATG-K2 in subacute intravaginal animal toxicity in Sprague-Dawley rats under OECD guidelines and GLP regulations. Toxicological assessments were performed in a single-dose toxicity study by intravaginal administration with local tolerance study, 1-week repeated-dose intravaginal toxicity dose range finding (DRF) study, and a 2-week repeated-dose intravaginal toxicity study with a 2-week recovery period. Studies were performed at dose 3-18 × 10⁹ CFU/head/day. No toxicological changes in clinical signs, body weight, water and food consumption, urinalysis, hematology, clinical biochemistry, gross findings, or histopathological examination were observed in intravaginal repeated-dose toxicity. And Lactobacillus plantarum ATG-K2 did not show any local tolerance at the same doses as the intravaginal repeated-dose toxicity study. In conclusion, the no-observed-adverse-effect level (NOAEL) of Lactobacillus plantarum ATG-K2 was 12 × 10⁹ CFU/head/day and no target organ was identified in female rats. Our findings are the first to suggest that Lactobacillus plantarum is safe for use as an intravaginal treatment with no adverse effects observed in toxicological testing and has potential for application as a therapeutic agent or for other biological uses.