Alleviative Effects of Low-Dose Lactulose Combined with Bacillus pumilus NJAUYBN1-7 on Slow Transit Constipation in Loperamide-Induced Mice

AIMS: Slow transit constipation (STC) is a common functional gastrointestinal disorder characterized by intestinal motility dysfunction, barrier damage, hormonal imbalance and gut microbiota dysbiosis. High-concentration (50%) lactulose is routinely used for STC treatment, while Bacillus pumilus acts as a probiotic to regulate intestinal flora. However, the synergistic efficacy and mechanism of low-dose lactulose combined with Bacillus pumilus NJAUYBN1-7 for STC remain unclear. This study aimed to clarify the therapeutic effects and underlying mechanisms of this combined therapy and compare its efficacy with conventional high-dose lactulose monotherapy. METHODS AND RESULTS: A loperamide-induced mouse STC model was applied for efficacy evaluation. Compared with 50% lactulose monotherapy, 30% lactulose combined with vegetative cells of Bacillus pumilus NJAUYBN1-7 (2.0 × 109 CFU·mL-1) significantly relieved constipation symptoms and shortened the first defecation time to 174.5 ± 9.14 min. Meanwhile, fecal output, fecal water content (52.08 ± 5.33%) and intestinal transit rate (49.38 ± 2.46%) were markedly increased. Mechanistically, the combination restored the SCF/Kit pathway, significantly upregulated the expression of intestinal barrier-related proteins (P < 0.05), normalized gastrointestinal hormone concentrations, alleviated colonic inflammation by reducing pro-inflammatory cytokine levels (P < 0.05), and remodeled gut microbiota homeostasis by altering the relative abundance of key enteric bacteria. CONCLUSIONS: 30% lactulose combined with Bacillus pumilus NJAUYBN1-7 exhibits superior STC therapeutic effects compared with 50% lactulose monotherapy. This synergistic regimen improves intestinal motility, repairs intestinal barrier, relieves inflammation and optimizes intestinal microenvironment via multi-target regulation. This study provides novel mechanistic insights and validates the clinical translational potential of this safe and efficient combined strategy for STC treatment.