Mechanism of Mulberry's Effect on Intestinal Flora and Motility

Abstract

Studies have indicated that mulberry consumption promotes intestinal motility and alleviates constipation, but the specific mechanism remains unclear. This study adopted a constipation mouse model to empirically analyze the effects of mulberry on intestinal motility, gut microbiota composition, and neurotransmitter levels, aiming to elucidate its mechanism of action. Key findings are as follows: 1) Compared with the model group, the treatment with mulberry extract significantly increased the moisture content of feces (MD). Among them, the increase in the high-dose group compared to MD was 137.5% (p< 0.05). It also accelerated the small intestine transport speed by 3.4 times and shortened the latency period for the first occurrence of black feces by 73.7% (p<0.05). These parameters were comparable to those of the untreated control group. 2) In the constipation model caused by dehydration and restraint together, six intestinal neurotransmitters changed. Mulberry administration restored the levels of acetylcholine (ACh), γ‑aminobutyric acid (GABA), serotonin (5‑HT), and Norepinephrine (NE) relative to the model group, while Glutamate (Glu) was reduced. 3) The 16S rRNA gene sequencing of the intestinal microbiota revealed that there were 21 species of bacterial genera with varying abundances among different groups. Correlation analysis linked their relative abundances to the levels of intestinal neurotransmitters and motility parameters. Among them, Dorea unclassified_f_Rikenellaceae was identified as the constipation-associated genus. 4) Correlation analyses linked the altered genera with both neurotransmitter concentrations and motility indices. Notably, Dorea (p < 0.05) and unclassified_f_Ruminococcaceae(p < 0.01) showed the most pronounced changes after mulberry intervention and were strongly associated with restored 5‑HT, Glu, NE, and ACh levels. Although Citrobacter, Oscillospira, and unclassified_f_Rikenellaceae remained unchanged, their baseline abundances correlated with constipation severity, suggesting potential biomarker roles. Collectively, these results demonstrate that mulberries markedly alleviate constipation in mice by restructuring the gut microbial ecosystem and normalizing intestinal neurotransmitter profiles, thereby enhancing peristalsis. Importantly, our integrated motility‑microbiome‑neurochemical data provide a novel mechanistic insight supporting the development of mulberry‑based adjunct therapies for constipation.