IntroductionThe study evaluates the preventive effects of Polygonatum sibiricum and Poria cocos (3:1) on spleen deficiency constipation in mice, focusing on the brain-gut axis, gut microbiota, and oxidative stress. The findings aim to inform the prevention and treatment of this condition.MethodsThirty male specific pathogen-free (SPF) KM mice (4 weeks old, 20 ± 2 g) were randomized into a normal control group (NC), a model group (NM), and a Polygonatum sibiricum and Poria cocos group (HF). Serum levels of 5-hydroxytryptamine (5-HT), cholecystokinin (CCK), motilin (MTL), and vasoactive intestinal peptide (VIP) were measured by ELISA. Liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by a spectrophotometer. Gut microbiota was analyzed by 16S rRNA sequencing.ResultsCompared to NM, the HF showed significantly increased 5-HT, CCK(p < 0.05), and MTL (p < 0.001), and significantly decreased VIP(p < 0.05). Liver MDA content was markedly higher in NM than in NC(p < 0.01), with a downward trend in HF. Conversely, the liver SOD activity in NM was significantly lower than in NC(p < 0.001), and the HF displayed an upward trend. Microbiota analysis revealed higher diversity in HF, as indicated by higher chao1, pielou_e, shannon, and simpson indices. The gut microbiota species composition in the HF was dominated by beneficial bacteria such as Bacteroidota and Faecalibaculum, with a reduction in pathogenic bacteria such as Proteobacteria and Escherichia-Shigella. The characteristic gut microbiota of the NM was enriched in Escherichia-Shigella and its conditional pathogens, while the characteristic gut microbiota of the HF was enriched in beneficial symbiotic bacteria such as Akkermansia, Blautia, and Bifidobacterium. The metabolic pathways and the genetic information processing pathway were improved in the HF, and the DNA repair and recombination protein pathways were also repaired.ConclusionThe P. sibiricum and P. cocos combination effectively prevents spleen deficiency constipation, an effect associated with the brain-gut axis and gut microbiota. The observed trends in oxidative stress markers warrant further investigation.