Researchers have identified indole metabolites from the human blood bacterium Paracoccus sanguinis that showed anti-aging activity in laboratory-grown human skin cells. The compounds reduced oxidative stress, inflammation and collagen-degrading activity in cell experiments, according to findings published in the Journal of Natural Products.
Scientists have uncovered a potential new source of anti-aging compounds within the human bloodstream.
A team led by Chung Sub Kim and Sullim Lee investigated Paracoccus sanguinis, a Gram‑negative, facultative anaerobic bacterium isolated from human blood and reported in 2015 as a producer of indole compounds.
Indole metabolites, a class of bacterial by-products, have drawn attention for their reported anti-inflammatory, anti-aging and antimicrobial activities, according to an American Chemical Society (ACS) news release and related journal materials.
Identifying new indole metabolites
To probe the bacterium’s chemistry, the researchers cultured a large quantity of P. sanguinis for three days and extracted the metabolites it produced. Using a combination of analytical methods — including spectrometry, isotope labeling and computational analysis — they determined the structures of 12 distinct indole-functionalized metabolites. Six of these compounds had not been documented previously.
"We became interested in P. sanguinis because blood-derived microbes are a relatively uncharted area of research," Kim said in remarks reported by the ACS. "Given the unique environment of the bloodstream, we believed that studying individual species like P. sanguinis could reveal previously unknown metabolic function relevant to health and disease."
Testing effects on skin cell aging processes
The team then examined whether the indole metabolites could influence biological processes linked to skin aging. They applied solutions of each compound to cultured normal human dermal fibroblasts, a type of skin cell, that had been pretreated to raise levels of reactive oxygen species (ROS), molecules known to promote inflammation and to damage collagen.
According to the ACS summary and the Journal of Natural Products paper, three of the 12 indole metabolites — including two of the newly identified compounds — showed notable anti-aging activity in these cell-based tests. In tumor necrosis factor alpha (TNF-α)-stimulated fibroblasts, the three metabolites:
- Suppressed reactive oxygen species (ROS)
- Reduced secretion of inflammatory cytokines interleukin-6 (IL‑6) and interleukin-8 (IL‑8)
- Lowered levels of matrix metalloproteinase-1 (MMP‑1), a protein involved in collagen degradation
These results indicate that specific P. sanguinis-derived indole metabolites can dampen oxidative and inflammatory responses and collagen-damaging activity under the experimental conditions used.
Early-stage implications for skin treatments
Based on these findings, the authors and ACS materials say the newly characterized metabolites are promising candidates for future strategies aimed at mitigating skin aging. The work remains at an early, preclinical stage, and the effects have so far been demonstrated only in cultured human skin cells rather than in animals or people.
The research, titled "Discovery and Biosynthesis of Indole-Functionalized Metabolites from the Human Blood Bacterium, Paracoccus sanguinis, and Their Anti-Skin Aging Activity," was published in the Journal of Natural Products (volume 88, issue 5, pages 1120–1129; DOI: 10.1021/acs.jnatprod.4c01354). Listed authors include Won Min Lee, Si‑Young Ahn, Gyu Sung Lee, InWha Park, Jonghwan Kim, Seung Hwan Lee, Sullim Lee and Chung Sub Kim.
The study was supported by the National Research Foundation of Korea, the BK21 FOUR Project and the National Supercomputing Center, according to ACS and journal disclosures.
