2′‐ FL 's Depiction of the Human Physiological Function Landscape

ABSTRACT

2′‐fucosyllactose (2′‐FL) is a major fucosylated human milk oligosaccharide characterized by a terminal α1,2‐linked fucose residue, which supports its interactions with gut microbes, host glycan‐recognition systems, and pathogen‐binding sites. This review proposes that 2′‐FL acts mainly through a hierarchical host–microbiota mechanism: it first shapes gut microbial composition, then influences microbial metabolites such as short‐chain fatty acids, and subsequently contributes to intestinal barrier integrity, immune homeostasis, and broader physiological outcomes. Current evidence is strongest for the safety of 2′‐FL‐containing infant formula, its bifidogenic effect, and its role in gut barrier and immune regulation. Preclinical studies further suggest potential benefits in allergy modulation through mast cell stabilization, suppression of Th2‐skewed responses, and enhancement of regulatory immune pathways, as well as inhibition of TLR4/NF‐κB‐mediated inflammation. However, antiviral, metabolic, and neuroprotective effects remain emerging and are mainly supported by in vitro, organoid, animal, or computational studies. By distinguishing clinical evidence from mechanistic and preclinical findings, this review aims to provide a structured and evidence‐based overview of the physiological functions and translational potential of 2′‐FL.