Synergistic effects of 2′-fucosyllactose and Akkermansia muciniphila in functional foods: enzymatic degradation mechanisms and therapeutic applications for gut health

Akkermansia muciniphila (A. muciniphila), a mucin-degrading bacterium and a highly regarded next-generation probiotic, performs multiple physiological functions such as maintaining gut homeostasis, regulating immunity, and modulating metabolism, and has been widely recognized as a potential therapeutic target for metabolic and inflammatory disorders. In recent years, studies have revealed that the core mechanism underlying the functional synergy between A. muciniphila and the host lies in its selective utilization of 2′-fucosyllactose (2′-FL), the most abundant component of human milk oligosaccharides (HMOs). Although the importance of A. muciniphila and 2′-FL in infant gut nutrition and metabolic health has been recognized, the molecular mechanisms of 2′-FL metabolism by A. muciniphila and the translational health benefits of this interaction remain understudied. To bridge these gaps, this review synthesizes current knowledge on the spatial distribution, host-microbe interactions, and functional adaptability of A. muciniphila. We further systematically examine the sources, biosynthetic pathways, and biological properties of 2′-FL, with a focus on the pivotal roles of glycoside hydrolases families (GHs)—including α-1,2-fucosidases from the GH29/95 family and β-galactosidases from the GH2/35 family—in 2′-FL degradation. Additionally, we explore how the resultant short-chain fatty acids (SCFAs) facilitate crosstalk between microbes and between the host and microbiota. Building on this integrated perspective of A. muciniphila-2′-FL interplay, we propose novel directions for designing targeted nutritional interventions and population-specific functional foods.