Cunninghamella elegans Cultivation on Agro-Industrial Residues and Assessment of Immunomodulatory Properties of Bioproducts in THP-1 Macrophages

Polyunsaturated fatty acids, particularly γ-linolenic acid, are recognized for their therapeutic and nutritional properties. Zygomycetes, such as Cunninghamella elegans , represent a promising microbial platform for sustainable gamma-linolenic acid (GLA) production as an alternative to conventional sources. Despite this potential, the immunomodulatory activity of metabolites from C. elegans has not been previously explored. In this study, C. elegans was cultivated on hydrolysates from discarded residues of Pleurotus spp. cultures (DRPC-HL), optimized to release assimilable compounds, promoting valorization of low-value biomass within a circular bioeconomy. Dry mycelial biomass, lipid-free biomass, and intracellular lipids from these cultures, alongside previously reported C. elegans cultures grown under nitrogen-excess (N-Xs) and nitrogen-limited (N-Lim) conditions, were tested on THP-1-derived macrophages, under lipopolysaccharide (LPS)-induced inflammatory conditions. Following in vitro gastrointestinal digestion, dry biomass and lipid-free dry biomass fractions upregulated the anti-inflammatory cytokine IL10 and downregulated IL1B and TNF , particularly from N-Xs and DRPC-HL cultures. Lipids mainly enhanced IL10 expression, especially when derived from N-Xs cultures. No changes were observed in upstream regulators ( TLR2 , TLR4 , NFKB1 , RELA ), suggesting a feasible post-receptor immunomodulatory action. Overall, these findings highlight the dual value of fungal bioproducts derived from agro-industrial residues, combining sustainable bioprocessing with bioactive compound generation, supporting environmentally friendly microbial platforms for industrial applications.