Pectin oligosaccharides from hawthorn attenuate constipation by modulating enteric neurotransmitters and gut microbiota

Dietary oligosaccharides can modulate the gut microbiota and elicit substantial health benefits. In this study, pectin oligosaccharides (HPOS) were prepared from hawthorn. However, the specific mechanism by which HPOS relieve constipation remains unclear. HPOS significantly improved defecation-related parameters in constipated mice, increasing the number of black feces, wet fecal weight, and gastrointestinal transit ratio by 71.4%, 46.8%, and 26.3%, respectively, compared with the model group. HPOS administration alleviated colonic inflammation by reducing the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Meanwhile, HPOS upregulated the expression of the tight junction proteins (ZO-1 and Occludin). Moreover, HPOS significantly elevated the levels of intestinal excitatory neurotransmitters and reduced those of inhibitory neurotransmitters. HPOS treatment shifted the expression profile of enteric neurotransmitter receptors by decreasing colonic vasoactive intestinal peptide receptor 1 (VIPR1) expression and increasing 5-hydroxytryptamine receptor 4 (HTR4) expression. After HPOS treatment, the relative abundances of intestinal genera such as Ruminococcus and Clostridium were markedly increased, accompanied by elevated contents of short-chain fatty acids (SCFAs). Importantly, fecal microbiota transplantation (FMT) from HPOS-treated donors reproduced the anti-constipation effects. In conclusion, HPOS could promote the defecation in mice through the regulation of intestinal neurotransmitters and gut microbiota, thereby providing experimental evidence to support subsequent human clinical trials.