Extracellular Vesicle‐Like Nanoparticles Present in Fermented Botanical Products Suppress Fat Absorption in the Gut

ABSTRACT The fermented botanical product (FBP) is a complex, primarily plant‐based fermented food that has been popular among consumers for many years. Although FBP may modulate gastrointestinal function, the responsible factors and precise mechanisms remain unclear and speculative. Extracellular vesicles (EVs) have gained widespread attention as a novel signaling system, not only in animals but also in plants and microorganisms. Here, we report that FBP contains EV‐like nanoparticles composed of protein complexes originating from various lactic acid bacteria. When mice consumed the EV‐like nanoparticle‐enriched fraction of FBP as a beverage for three weeks, their body weight gain was reduced by up to approximately 10%, particularly in those fed a high‐fat/high‐sucrose (HF/HS) diet. Although the HF/HS diet induced colonic atrophy in mice, the ingestion of the EV‐like nanoparticles‐enriched fraction of FBP increased lipid efflux in feces by more than two‐fold and improved the pathological images of the colon. In vitro experiments on lipase activity suggested lipase inhibitory activity in the EV‐like nanoparticle‐enriched fraction of FBP. Compound analyses revealed that ferulic acid was enriched in the EV‐like nanoparticle fraction and inhibited lipase activity in vitro. The biological effects observed in this study were attenuated by reducing the amount of EV‐like nanoparticles using a polytetrafluoroethylene (PTFE) membrane. However, the slight reduction (not statistically significant) in bioactivity in the PTFE‐treated group compared with the polyether sulfone (PES) treated group, despite a marked decrease in ferulic acid content, suggests the possible involvement of additional molecules beyond EV‐like nanoparticles in this fraction. These findings indicate that FBP may serve as a potential therapeutic option for obesity and gastric symptoms. Practical Applications Extracellular vesicle‐like nanoparticles in FBP may support health by alleviating obesity through the suppression of excessive intestinal lipid uptake. These findings suggest that FBP could be developed into a functional food or supplement for individuals who frequently consume high‐fat diets.