| Summary: | NUTRIOSE<sup>®</sup> (Roquette, Lestrem, France) is a resistant dextrin with well-established prebiotic effects. This study evaluated the indirect effects of pre-digested NUTRIOSE<sup>®</sup> on host immune response and gut barrier integrity. Fecal samples from eight healthy donors were inoculated in a Colon-on-a-plate<sup>®</sup> system (ProDigest, Ghent, Belgium) with or without NUTRIOSE<sup>®</sup> supplementation. Following 48 h fermentation, colonic suspensions were tested in a Caco-2/THP1-Blue™ co-culture system to determine their effects on gut barrier activity (transepithelial electrical resistance) and immune response following lipopolysaccharide stimulation. Additionally, changes in short-chain fatty acid levels (SCFA) and microbial community composition following a 48 h fermentation in the Colon-on-a-plate<sup>®</sup> system were measured. Across all donors, immune-mediated intestinal barrier damage was significantly reduced with NUTRIOSE<sup>®</sup>-supplemented colonic suspensions versus blank. Additionally, IL-6 and IL-10 levels were significantly increased, and the level of the neutrophil chemoattractant IL-8 was significantly decreased with NUTRIOSE<sup>®</sup>-supplemented colonic suspensions versus blank in the co-culture models following lipopolysaccharide stimulation. These beneficial effects of NUTRIOSE<sup>®</sup> supplementation were likely due to increased acetate and propionate levels and the enrichment of SCFA-producing bacteria. NUTRIOSE<sup>®</sup> was well fermented by the colonic bacteria of all eight donors and had protective effects on inflammation-induced disruption of the intestinal epithelial barrier and strong anti-inflammatory effects.
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