Fermentation of Plant Extracts Supplemented with Milk Components by Lactic Acid Bacteria Produces Soluble Agonists for Toll-like Receptor 2 Possibly Suitable for Cosmetics

Stimulation of Toll-like receptor 2 (TLR2) on epidermal keratinocytes results in the tightening of cell–cell junctions between keratinocytes; therefore, appropriate agonists for TLR2 could be promising ingredients for cosmetics. However, a method to produce significant amounts of soluble TLR2 agonists using materials that are suitable for preparing cosmetics has not yet been developed. In this study, we tried to identify appropriate lactic acid bacterial strains and media for fermentation to obtain soluble TLR2 agonists from traditional fermented foods and natural food sources. We found that Lactobacillus delbrueckii subsp. lactis TL24 (TL24) and a combination of hot water extracts of asparagus edible stem and cow skimmed milk were the best strain and culture medium, respectively, for this purpose. The TL24 ferments effectively stimulated TLR2 in HEK293 reporter cells expressing human TLR2 on their surface and also inhibited paracellular molecular transfer in a cell sheet of human primary keratinocytes. Since these effects of the TL24 ferments were suppressed by anti-TLR2 neutralizing antibodies, it is proposed that TL24 ferments elicit these effects via TLR2. Taken together, these results suggest that TL24 ferments containing soluble TLR2 agonists are potential ingredients for cosmetics.