Yeast–Plant-Derived Consortia Factors Exhibit an Enriched Extracellular Metabolome with Antioxidant and Anti-Inflammatory Potential in Human Skin-Derived Cells

Cells secrete metabolites and other bioactive factors into the extracellular environment, collectively known as the secretome. While single-species secretomes are well studied, the impact of interspecies co-culture on secretome composition remains poorly understood. Here, we investigated whether co-culturing plant and yeast cells could generate emergent secretory outputs. A yeast suspension of Ustilago cynodontis was co-cultured with plant cells derived from Ocimum sanctum (Tulsi) to produce a novel set of secretory factors termed Consortia Factors (CFx). Metabolomic profiling of the Ustilago-Tulsi CFx, termed CFx-α1, revealed a metabolome that was distinct from and more enriched than those of either monoculture. Statistical clustering demonstrated divergence from single-culture secretomes, with approximately one-third of enriched metabolites absent from either organism grown alone. Using an algorithm designed to identify validated antioxidant and anti-inflammatory metabolites, we found that CFx-α1 was significantly enriched in these metabolites, including vitamin C. Consistent with this profile, CFx-α1 exhibited greater intracellular antioxidant activity and more effectively attenuated lipopolysaccharide (LPS)-induced NF-κB nuclear localization in human skin-derived cells than either single-culture conditioned medium. CFx-α1 also maintained human dermal fibroblast viability across concentrations of 1–5%. These findings indicate that plant–yeast co-culture generates a distinct and functionally enriched extracellular metabolome with antioxidant and anti-inflammatory potential, highlighting consortia-based culture systems as a promising strategy for producing bioactive metabolites for cosmetic applications.