Postbiotics produced by beneficial bacteria are emerging as safe dietary approaches to intestinal inflammation. We evaluated intestinal bacterial metabolites (IBM), a cell-free fermented soybean extract generated by co-culturing 31 Lactobacillus/Bifidobacterium-related strains, for prophylactic protection in 3% dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6NJ mice received oral IBM (0.4 or 2 mL/kg/day) or vehicle for 7 days before and during 7 days of DSS. Disease activity index (DAI), colon length, and histopathology were assessed, and endpoint serum cytokines were quantified by a multiplex bead assay. DSS-independent responses were examined in healthy mice after 7 days of IBM by rectal RNA sequencing and cecal 16S rDNA profiling, and direct epithelial effects were tested in HCT-116 and DLD-1 cells treated with 2% IBM. IBM attenuated colitis, improving DAI, preventing colon shortening, and ameliorating histopathology, with decreased IL-23 and IL-17A and increased IFN-β and GM-CSF. Rectal transcriptomics showed modulation of circadian programs, upregulation of mucosal/barrier genes, and reduced extracellular-matrix remodeling signatures. IBM increased junctional proteins and barrier-related transcripts in vitro and shifted the microbiota, increasing Lactobacillus and Roseburia while decreasing Streptococcus and Staphylococcus. These coordinated clinical, immunological, transcriptomic, epithelial, and microbiome changes support prophylactic protection by IBM against DSS colitis.

Background/Objective: Dendritic cells (DCs) act as sentinels bridging innate and adaptive immunity, and their functions are strongly influenced by dietary and environmental factors. Phytochemicals such as α-Mangostin (A phytochemical, a xanthone derivative from Garcinia mangostina, known for its anti-inflammatory and antioxidant properties) are widely recognized for their antioxidant and anti-inflammatory effects, but their potential to modulate antiviral pattern recognition pathways remains unclear. This study investigated whether phytochemicals activate retinoic acid–inducible gene I (RIG-I: DDX58, a cytosolic receptor recognizing viral RNA and inducing antiviral responses)–dependent signaling in human monocyte-derived dendritic cells (MoDCs) and affect downstream T cell responses. Methods: MoDCs were generated from peripheral blood and stimulated with selected phytochemicals. RIG-I pathway–related transcripts were quantified by qPCR, and protein expression was assessed by Western blotting, intracellular flow cytometry, and immunofluorescence staining. Functional outcomes were evaluated by co-culturing MoDCs with T cells, followed by phenotypic analysis via flow cytometry and measurement of IFN-γ production by ELISA. Results: α-Mangostin stimulation increased RIG-I (DDX58) mRNA levels in MoDCs and induced time-dependent changes in intracellular protein expression. In co-culture, α-Mangostin–treated MoDCs tended to increase the proportion of OX40⁺ 4-1BB⁺ CD4⁺ T cells, accompanied by a significant elevation of IFN-γ levels in supernatants. Experiments with CpG-ODN (synthetic oligodeoxynucleotides mimicking bacterial DNA that activate TLR9) suggested context-dependent crosstalk between the TLR9 and RIG-I signaling axes. Conclusions: Phytochemicals, exemplified by α-Mangostin, prime antiviral responses in human DCs through upregulation of RIG-I and promote Th1-dependent immune responses. These findings suggest that phytochemicals may represent promising nutritional strategies to enhance antiviral immunity while mitigating excessive inflammation under infectious conditions.