Comparative impact of white and black garlic on intestinal homeostasis: barrier protection, inflammation and microbiota modulation

Thermal aging transforms white garlic (WG) into black garlic (BG), potentially modifying its biological activity; however, its effects on intestinal barrier function and host-microbiota interactions remain insufficiently characterized. This study compared WG and BG extracts in terms of composition, antioxidant capacity, antimicrobial activity, cytocompatibility and modulation of intestinal homeostasis in a lipopolysaccharide (LPS)-challenged Caco-2/HT29 co-culture in vitro model. On a dry basis, aging decreased reducing sugars (∼39 to ∼33 g/100g), while markedly increasing antioxidant content and capacity, including total phenolics (∼111 to ∼433 mg gallic acid equivalents/g), proanthocyanidins (∼689 to ∼1423 mg catechin equivalents/g) and ferric reducing antioxidant power (∼23 to ∼136 mmol Fe2+/g). Untargeted metabolomics revealed a compositional shift from amino acid- and sulfur-enriched metabolites in WG toward organic acids and nitrogen-containing compounds in BG. BG extract exerted minimal inhibitory effects against probiotic strains (Escherichia coli Nissle, 1917 and Lacticaseibacillus paracasei) and exhibited greater cytocompatibility (>80% at 1 mg/mL WG; >100% at 10 mg/mL BG). Both extracts significantly reduced LPS-induced interleukin-6 production (84 ± 5% for BG; 89 ± 24% for WG). Notably, BG more effectively preserved epithelial barrier integrity by maintaining transepithelial electrical resistance (TEER), reducing paracellular permeability and preserving zonula occludens-1 (ZO-1) organization. These findings support BG as a functional ingredient for mitigating inflammation-associated intestinal barrier dysfunction.