The double-edged sword effect of galactoglucomannan-rich Norway spruce (Picea abies) byproduct extract in mice with induced colitis.

Abstract

Galactoglucomannan (GGM) is a hemicellulosic polysaccharide with emerging prebiotic and immunomodulatory properties. Here, we evaluated the protective potential and biological effects of a Norway spruce byproduct extract (NSBE), a forestry-derived fraction rich in GGM and phenolic compounds, in dextran sulfate sodium (DSS)-induced acute colitis and under homeostatic conditions, focusing on inflammation, oxidative stress, intestinal barrier integrity, and gut microbiota, while also using complementary in vitro models to explore the underlying mechanisms. In vitro, NSBE exhibited selective cytotoxicity toward colorectal cancer cells (Caco-2) and cell line-dependent redox effects, showing antioxidant activity in Caco-2 cells associated with the preservation of epithelial monolayer integrity under inflammatory challenge, while inducing a pro-oxidant response in colon fibroblasts (CCD-18Co). In vivo, NSBE treatment (400 mg/kg/day) during DSS-induced colitis did not prevent disease activity or intestinal barrier disruption, although it restored growth performance in mice. Under these conditions, NSBE administration reduced colonic malondialdehyde levels, attenuated TNF-α and IL-6 expression in the liver and colon, and modulated IL-10 production in splenocyte cultures under both unstimulated and stimulated conditions. These effects were accompanied by microbiota remodeling, characterized by increased Bacteroidetes abundance, reduced Gammaproteobacteria abundance, and enhanced acetic acid production. Under homeostatic conditions, NSBE altered inflammatory gene expression and redox balance while increasing bacterial translocation without affecting epithelial permeability. These findings indicate that GGM-containing NSBE exerts context-dependent effects on oxidative balance, inflammation, and host-microbiota interactions, underscoring both the therapeutic potential and inherent risks associated with the use of forestry-derived byproducts as nutraceutical candidates for inflammatory bowel diseases (IBD) management.