The Anti-Constipation Effect of Garlic Polysaccharides: Roles of Gut Barrier Integrity, VIP Pathway, and the Microbiota-SCFAs Axis.

The global prevalence of functional constipation has witnessed a marked increase due to the imbalanced dietary pattern. The prebiotic function in vitro and the anti-constipation efficacy of garlic polysaccharides (GP) in loperamide-induced constipated mice were evaluated. During in vitro simulated digestion and fecal fermentation, GP showed digestive resistance properties and enhanced abundance of the probiotic bacteria Bifidobacterium and Lactobacillus. In vivo, GP significantly attenuated intestinal oxidative stress. Moreover, GP treatment dose-dependently ameliorated constipation parameters. Notably, GP restored colonic barrier integrity: GP potently upregulated the mRNA expression of tight junction proteins ZO-1 and occludin in the mechanical barrier and exhibited the most substantial restoration of both MUC2 and MUC4 expression levels in the mucins barrier, as well as reduced pro-inflammatory cytokines of TNF-α, IL-1β, IL-17 and elevated anti-inflammatory IL-10 in the immune barrier. Furthermore, GP regulated VIP-cAMP-PKA-AQP3 signaling pathway, which subsequently promoted intestinal water transport and mucus secretion. GP significantly regulated the gut microbiota-SCFAs axis by lowering the Firmicutes/Bacteroidetes ratio and suppressing the level of pathobiont Desulfovibrio. GP intervention significantly elevated total SCFAs compared to the MOD group (p < 0.05). These results elucidated GP's multi-target mechanism against functional constipation via antioxidant, barrier-repairing, VIP pathway-regulating, and microbiota-directed SCFAs axis.