Probiotics have garnered increasing attention as a potential therapeutic approach for type 2 diabetes mellitus (T2DM). Previous studies have confirmed that Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) could stimulate the secretion of glucagon-like peptide-1 (GLP-1) in NCI-H716 cells, but whether MN-Gup has a hypoglycemic effect on T2DM in vivo remains unclear. In this study, a T2DM mouse model was constructed, with a high-fat diet and streptozotocin in mice, to investigate the effect of MN-Gup on diabetes. Then, different doses of MN-Gup (2 × 10⁹ CFU/kg, 1 × 10¹⁰ CFU/kg) were gavaged for 6 weeks to investigate the effect of MN-Gup on glucose metabolism and its potential mechanisms. The results showed that a high-dose of MN-Gup significantly reduced the fasting blood glucose (FBG) levels and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM mice compared to the other groups. In addition, there were significant increases in the short-chain fatty acids (SCFAs), especially acetate, and GLP-1 levels in the MN-Gup group. MN-Gup increased the relative abundance of Bifidobacterium and decreased the number of Escherichia-Shigella and Staphylococcus. Moreover, the correlation analysis revealed that Bifidobacterium demonstrated a significant positive correlation with GLP-1 and a negative correlation with the incremental AUC. In summary, this study demonstrates that Bifidobacterium animalis subsp. lactis MN-Gup has significant hypoglycemic effects in T2DM mice and can modulate the gut microbiota, promoting the secretion of SCFAs and GLP-1.

Given the probiotic effects previously found in Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) and its great application potential in dairy products, this study aimed to investigate the effects of fermented milk containing MN-Gup or MN-Gup-based synbiotics on high fat diet (HFD)-induced obesity in rats. Galacto-oligosaccharides (GOS) and xylo-oligosaccharides (XOS) were selected as the tested prebiotics in MN-Gup-based synbiotics due to their promotion of MN-Gup growth in vitro. After nine weeks of HFD feeding, the obese rats were intervened with fermented milk containing MN-Gup (MN-Gup FM) or its synbiotics (MN-Gup + GOS FM, MN-Gup + XOS FM) for eight weeks. The results showed that the interventions could alleviate HFD-induced body weight gain, epididymal fat deposition, adipocyte hypertrophy, dyslipidemia and inflammation, but GOS and XOS did not exhibit significant synergies with MN-Gup on those alleviations. Furthermore, the interventions could regulate the HFD-affected gut microbiota and microbial metabolites, as shown by the increases in short chain fatty acids (SCFAs) and alterations in obesity-related bile acids (BAs), which may play important roles in the mechanism underlying the alleviation of obesity. This study revealed the probiotic effects of MN-Gup on alleviating obesity and provided the basis for MN-Gup applications in the future.

Most Bifidobacterium species exhibit poor stress tolerance, which greatly limits their stability and industrial application. In contrast, Bifidobacterium animalis shows remarkable tolerance and distinct species-specific characteristics. Here, the survival rate of 17 strains from six Bifidobacterium species was evaluated under pH 2.5 for 2 h. All strains of B. animalis maintained survival rates above 60%, whereas other species fell below the detection limit. Comparative genomic analysis among B. animalis, B. breve, B. longum, and B. bifidum revealed 328 unique genes that were conserved across B. animalis strains but absent in the other species. Transcriptomic analysis of the B. animalis subsp. lactis A6 strain under acid stress identified ten genes that were significantly upregulated at both early and late stages of exposure. Homologous overexpression confirmed that four of these genes markedly enhanced survival under acid stress. Among them, BAA6_RS00480, encoding a GlsB/YeaQ/YmgE family stress response membrane protein, increased the survival rate by more than 22-fold. These findings provide new insight into the species-specific genetic mechanisms underlying the exceptional acid tolerance of B. animalis.