Exploring the Postbiotic Potential of Zygosaccharomyces bailii KAV1 from Kombucha

Introduction Postbiotics are increasingly recognized as key mediators of microbiome-driven health effects, representing a promising alternative to live microorganisms in functional foods and nutraceutical applications. While most research has focused on bacterial systems, particularly lactic acid bacteria, the contribution of yeasts remains largely underexplored. This gap is particularly relevant in fermented foods, where yeasts coexist with bacteria and actively contribute to metabolite production. Kombucha, a complex fermented beverage, represents a model ecosystem in which yeast-derived metabolites may play an important but still poorly characterized role. Among these, Zygosaccharomyces bailii is a stress-tolerant yeast widely distributed in food environments and frequently detected in kombucha fermentations. Despite its well-known technological properties, including resistance to low pH and high sugar concentrations, its potential as a source of bioactive postbiotic compounds has not been systematically investigated. Given its recurrent exposure to humans through fermented foods and its metabolic versatility, Z. bailii represents a promising candidate for the production of functional metabolites. This study aimed to evaluate the postbiotic potential of a kombucha-derived Z. bailii strain (KAV1), with a particular focus on antioxidant activity, modulation of immune responses, and effects on intestinal barrier integrity, key aspects of host–microbiome interactions. Methods KAV1 was isolated from commercial kombucha and identified by ITS sequencing. Cell-free supernatants were obtained after growth in minimal medium and plant-based matrices (tea and chamomile). Safety was evaluated via hemolytic activity. Metabolite profiles were characterized by GC–MS, while antioxidant capacity was assessed using the DPPH radical scavenging assay. Intestinal barrier integrity was evaluated in Caco-2 cells using transepithelial electrical resistance (TEER). Immunomodulatory effects were investigated in human PBMCs by measuring cytokine production in CD4⁺ T cells following stimulation. Results KAV1 showed no hemolytic activity, supporting its safety profile. Metabolomic analysis revealed substrate-dependent production of bioactive compounds, including short-chain and branched-chain fatty acids and phenylethyl alcohol. Supernatants significantly enhanced antioxidant activity in minimal medium compared to controls (p < 0.0001), with moderate effects in plant-based substrates. Notably, KAV1 metabolites significantly reduced the frequency of IFNγ⁺ CD4⁺ T cells (p < 0.05), indicating a targeted anti-inflammatory effect comparable to the probiotic yeast Saccharomyces boulardii. Preliminary TEER data further suggest a protective effect on intestinal barrier integrity, as KAV1 supernatants improved Caco-2 monolayer resistance following inflammatory challenge with TNF-α and IL-1β, indicating a potential role in restoring epithelial function under stress conditions. Discussion This study provides novel evidence that Z. bailii, a non-conventional yeast, can act as a source of functional postbiotic metabolites with measurable effects on oxidative stress and immune responses. Importantly, the observed immunomodulation highlights a previously unrecognized role of yeast-derived compounds in shaping host inflammatory pathways. These findings expand the current postbiotic paradigm beyond bacterial systems and support the inclusion of yeasts as relevant contributors to microbiome-associated health benefits. Given its widespread presence in fermented foods, Z. bailii represents a promising candidate for the development of next-generation functional ingredients.