Fungal Solid-State and Submerged Fermentation of Blueberry Bagasse: Extraction Strategies, Phenolic Profiling, and Cellular Immunomodulation

Solid-state and submerged fermentation (SSF and SmF) were evaluated as bioprocessing strategies to enhance the recovery and bioactivity of phenolic compounds from blueberry bagasse. Fermentation was performed using Aspergillus niger ATCC 6275 and Rhizopus oryzae BIOTEC018, alongside non-inoculated controls. Extracts (SmF filtrate, buffer, methanol, and buffer-methanol) were obtained and analyzed for total phenolic content (TPC), total anthocyanins, and antioxidant capacity over 0–60 h. Methanolic extracts obtained after 24 h of SSF were further selected for profiling of individual phenolics and for intracellular reactive oxygen species (ROS), nitric oxide (NO), and cytokine responses. Compared with SmF and non-inoculated controls, SSF—particularly when combined with methanolic extraction—was associated with modified phenolic recovery patterns at 24 h, including increases in TPC and differences in anthocyanin preservation. SSF promoted the accumulation of phenolic acids and flavan-3-ols, together with improved preservation of major anthocyanins. These compositional changes translated into higher antioxidant capacity and a marked reduction in ROS and NO levels (≈40–60% of oxidant or LPS controls). Cytokine responses were strain-dependent, indicating regulated immune modulation rather than generalized inflammation. Overall, fungal SSF combined with methanolic extraction modulated the phenolic profile and associated biological responses of blueberry bagasse under laboratory conditions.