2'-Fucosyllactose synbiotics with Bifidobacterium bifidum to improve intestinal transcriptional function and gut microbiota in constipated mice.

Probiotics, prebiotics, and synbiotics are potential therapeutic options for constipation. However, the synergistic effects and underlying mechanisms of 2'-fucosyllactose (2'-FL) and Bifidobacterium bifidum (B. bifidum) in ameliorating constipation remain unclear. In this study, constipated mice were treated 2'-FL combined with B. bifidum, and their effects were evaluated based on defecation performance, gastrointestinal regulatory peptide levels, intestinal inflammation, and barrier function. Transcriptomics and 16S rRNA sequencing were performed to assess gene expression and gut microbiota composition, respectively. The results demonstrated that 2'-FL + B. bifidum enhanced intestinal secretion of gastrin and substance P while suppressed vasoactive intestinal peptide, improving defecation parameters. Furthermore, 2'-FL + B. bifidum significantly reduced the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 while increasing IL-10 levels. It also upregulated intestinal tight junction proteins (ZO-1, Claudin-1, and Occludin) and reduced serum markers of intestinal permeability (D-lactic acid, enterotoxin, and diamine oxidase). Transcriptomic analysis revealed that 2'-FL + B. bifidum upregulated genes related to the immune system processes, signaling pathways, ABC transporters, glycolysis/gluconeogenesis, and butanoate metabolism. Furthermore, our results demonstrated that 2'-FL + B. bifidum could regulate the composition of the gut microbiota in constipated mice, promoting the growth of beneficial intestinal bacteria, such as Akkermansia, Bifidobacterium, and Parabacteroides. In summary, 2'-FL + B. bifidum alleviates constipation in mice by regulating intestinal transcriptional profiles and the gut microbiota composition. This study provides theoretical support for the development and application of synbiotics containing 2'-FL and B. bifidum.