**4. Conclusions**

Overall, in comparison with natural bee pollen, enzyme-treated bee pollen can reduce mice scratching frequency, spleen pathological injury, and serum IgE production. Moreover, it can additionally regulate bioamine serum levels, as well as modulate steroid biosynthesis and butanoate metabolism. Further, enzyme-treated bee pollen can regulate the composition of gut microbial structures by increasing the abundance of *Lachnospiraceae*, *Marinifilaceae* and *Helicobacteraceae*, while decreasing the abundance of *Bacillaceae* and *Akkermansiaceae*, which are involved in allergenicity mitigation. The findings suggest that enzymatic treatment has an alleviatory effect on the allergenicity of bee pollen, and provide a scientific basis for further development and utilization of hypoallergenic bee pollen products.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/foods11213454/s1, Table S1. The parameters for bioamines detection by UPLC-QQQ-MS/MS.

**Author Contributions:** Conceptualization, Q.L. and L.W.; Data curation, F.L. and L.M.; Formal analysis, Y.T. and E.Z.; Funding acquisition, Q.L. and L.W.; Investigation, Y.T. and E.Z.; Methodology, Q.L. and L.W.; Project administration, Q.L. and L.W.; Supervision, Q.L. and L.W.; Validation, F.L. and L.M.; Visualization, Y.T. and E.Z.; Writing—original draft, Y.T. and E.Z.; Writing—review and editing, Q.L. and L.W. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the National Natural Science Foundation of China (No. 32102605), and the Agricultural Science and Technology Innovation Program under Grant (CAAS-ASTIP-2020-IAR).

**Institutional Review Board Statement:** The animal study protocol was approved by the Animal Ethics Committee of Institute of Apicultural Research, Chinese Academy of Agricultural Sciences (Beijing, China) (protocol code: CAAS-IAR-ER0046, approval data: 25 August 2021).

**Data Availability Statement:** Data available on request due to privacy.

**Conflicts of Interest:** The authors declare no conflict of interest.
