母乳低聚糖(human milk oligosaccharides,HMOs)是母乳中第三大固体成分,具有多种生理功能,现有研究表明其对婴儿肠道中双歧杆菌属的定植具有重要意义。前期研究聚焦于2′-岩藻糖基乳糖(2′-fucosyllactose,2′-FL)或乳糖-N-四糖(lacto-N-tetraose,LNT)等个别HMO的菌株代谢特性,该研究利用高效液相色谱质谱联用靶向代谢技术首次系统揭示5株双歧杆菌(长双歧杆菌婴儿亚种FHBSJZ50M1、长双歧杆菌长亚种CCFM752、两歧双歧杆菌FJSWX9M8、短双歧杆菌FHuNCS1M5及齿双歧杆菌FGZ15I1M1)对2′-FL、LNT及其等比例混合物的动态代谢差异。结果显示,实验所用菌株均能利用单一及混合母乳低聚糖,但其生长效率和代谢物图谱呈现显著种间差异,长双歧杆菌长亚种CCFM752能通过对2′-FL的优先级利用在双歧杆菌群落中占据主导地位。该研究揭示了双歧杆菌通过底物优先级代谢和代谢产物调控双途径塑造菌群结构,并强调了2′-FL的生态调控功能,为解析HMOs-双歧杆菌精准配伍提供了菌株级代谢证据,并为婴幼儿配方食品中益生菌-HMOs组合的精准适配奠定了理论基础。
Human milk oligosaccharides (HMOs), the third most abundant solid component in human milk, play critical roles in infant gut microbiota development, particularly in promoting Bifidobacterium colonization.While previous studies focused on single HMO metabolism, this study systematically investigated the dynamic metabolism of 2′-fucosyllactose (2′-FL), lacto-N-tetraose (LNT), and their iso-mass mixtures by five Bifidobacterium strains (B.longum subsp.infantis FHBSJZ50M1, B.longum subsp.longum CCFM752, B.bifidum FJSWX9M8, B.breve FHuNCS1M5, and B.dentium FGZ15I1M1) using HPLC-MS-based targeted metabolomics.All strains utilized both single and mixed HMO(s), but exhibited significant interspecies differences in growth efficiency and metabolite profiles.B.longum subsp.longum CCFM752 dominated the bifidobacterial community (86.25% relative abundance at 48 h) by prioritizing 2′-FL utilization, achieving over 50% substrate consumption within 8 hours.Mechanistic analysis revealed that competitive advantages stemmed from two pathways:(1) intracellular 2′-FL metabolism via ABC transporters to avoid extracellular competition, and (2) cross-feeding on hydrolytic byproducts (e.g., L-fucose) generated by extracellular enzymes of co-cultured strains.These findings demonstrate that bifidobacteria shape microbial communities through substrate prioritization and metabolite regulation dual strategies, highlighting 2′-FL as a key ecological modulator.This study provides strain-level metabolic evidence for rational synbiotic design and supports precision matching of probiotic-HMO combinations in infant formula.
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