Abstract

Chronic constipation is a prevalent functional gastrointestinal disorder with limited long-term treatment options. This study examined whether a fucoidan preparation derived from Sargassum fusiforme (SF) ameliorates loperamide (LOP)-induced constipation in male ICR mice. SF was administered by oral gavage at 50, 100 or 200 mg/kg/day for 35 days, and constipation was induced with LOP (5 mg/kg) during the final 7 days; the design is therefore preventive rather than therapeutic. Defecation endpoints were recorded at the cage level (n = 3 cages per group) and fecal moisture in individual mice (n = 7 per group), whereas colonic cytokine and myeloperoxidase (MPO) measurements (n = 3–4 per group) and Western blot analyses (n = 3 per group) were performed in a small subset of animals, and histological analyses in n = 6–8 per group. SF increased fecal output and fecal moisture content with increasing dose; at 200 mg/kg the relative fecal number returned to the level of the Vehicle control group, although the absolute daily pellet count remained lower than that of the Vehicle control and of the Positive control group. SF administration was associated with lower colonic TNF-α, IL-6, IL-1β and MPO concentrations, with reduced phosphorylation of p38, JNK and ERK, with higher C-kit and stem cell factor (SCF) levels, with normalization of the LOP-induced increase in aquaporin-3 (AQP3), and with recovery of colonic mucosal thickness and mucin content. 16S rRNA gene sequencing showed a shift in fecal microbiota community structure (PERMANOVA p = 0.0002) and a dose-related increase in the combined relative abundance of Lactobacillus and Bifidobacterium, without a reduction in alpha diversity. These findings indicate that SF ameliorates LOP-induced constipation in male mice and that this effect is accompanied by changes in colonic inflammatory signaling, motility-related protein expression, mucosal architecture and gut microbiota composition.

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