Therapeutic Potential of 6-Hydroxycaproic Acid: a Metabolite of Streptococcus Gordonii

Objectives: We have previously demonstrated that Streptococcus gordonii spent culture supernatant (Sg-SCS) suppresses the growth and attachment of the keystone periodontal pathogen Prophyromonas gingivalis, as well as the red complex Treponema denticola. Sg-SCS also reduces IL-1β, IL-6, and IL-8 transcript and protein levels in cells challenged with P. gingivalis lipopolysaccharide (Pg-LPS). These results indicate that certain metabolites in Sg-SCS may be candidate biologics to suppress bacterial and inflammatory conditions of periodontal disease. In this study, we aim to identify the specific metabolites responsible for those anti-bacterial and anti-inflammatory effects using cell culture modules to develop a therapeutic treatment for periodontitis.
Methods: 6-hydroxycaproic acid (HCA), a medium chain fatty acid, is a metabolite that was found to be significantly increased in Sg-SCS using untargeted metabolomics. The effects of HCA on periodontal bacterial growth and pro-inflammatory cytokine expression in Pg-LPS-challenged human periodontal and immune cells were investigated through use of cell culture studies using HCA-incorporated culture medium. MTT assays were also performed to evaluate the effect of HCA on cellular toxicity.
Results: HCA presents no toxicity to human gingival fibroblasts and monocyte-derived macrophages. Similar to Sg-SCS, HCA reduced the growth of T. denticola and Streptococcus oralis. HCA also reduced the expression of IL-1b, IL-6, and IL-8 in human gingival fibroblasts and monocyte-derived macrophages challenged with Pg-LPS.
Conclusions: HCA suppresses the growth of pathogenic periodontal bacteria and demonstrates anti-inflammatory effects with no cellular toxicity, indicating its therapeutic potential for treating periodontal disease.