Effects of Fermented on Intestinal Barrier Integrity and Immunomodulation in a Lipopolysaccharide-Induced Colonic Model

: This study investigates the impact of fermentation supernatants (FSs) from whole mushrooms (PEWS), as well as its subcomponents, digested (PEWSD) and extracted (PEWSE) forms, on intestinal barrier function and immune modulation in lipopolysaccharide (LPS) -stimulated Caco-2 cells. : Gene expression of tight junction (TJs) genes, cytokines, and key immune/metabolic receptors was assessed via qRT-PCR, while cytokine protein levels were measured using ELISA to explore post-transcriptional regulation. : LPS challenge significantly downregulated TJs -1 (,) , and , compromising epithelial integrity. Treatment with FS-PEWS notably restored and expression, outperforming FS-PEWSD and FS-PEWSE, which only partially mitigated the LPS-induced damage. FS-PEWS further demonstrated potent immunomodulatory effects, upregulating anti-inflammatory and pro-inflammatory cytokines such as and . The activation of key receptors like and suggests that FS-PEWS modulates critical immune and metabolic pathways, such as signaling, to maintain immune homeostasis. Although mRNA expression of pro-inflammatory cytokines was altered, no corresponding protein release was detected, suggesting potential post-transcriptional regulation. : FS-PEWS preserves intestinal barrier integrity and modulates immune responses, particularly in low-grade inflammation, highlighting the whole food matrix's role in enhancing its bioactivity and functional food potential.