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Species-specific tryptophan metabolism drives bioactivity divergence in Apis cerana and Apis mellifera honeys

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Recently, the researchers from Food Nutrition and Functional Food Innovation Team at the Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (IFST-CAAS), revealed the metabolic driving mechanisms responsible for the differences in biological activities between Apis cerana (A. cerana) and Apis mellifera (A. mellifera) honey. The research finding has been published in the Journal of Advanced Research (JCR Q1, IF=13.0). Liu Yan, a master's student, is the first author of the paper. Professor Jinhui Zhou and Professor Fengzhong Wang from IFST, along with Associate Professor Xinran Wang from Beijing Academy of Agriculture and Forestry Sciences, served as the co-corresponding authors.

The honeys produced by A. mellifera and A. cerana are the two predominant varieties in terms of global yield, each recognized for its distinct functional properties. Our previous studies identified the characteristic markers distinguishing A. cerana honey and A. mellifera honey. However, the mechanistic links between species-specific metabolism and functional properties remain unclear, presenting a formidable challenge. This study aimed to elucidate how bee species-specific metabolism shapes honey bioactivity.

The researcher used topological and enrichment analyses to map the characteristic markers onto metabolic pathways, quantified the in vitro antioxidant capacity of both honeys and their respective markers via DPPH and ABTS radical scavenging assays. They further evaluated the anti-inflammatory efficiency of these honeys in lipopolysaccharide-stimulated Caco-2 cells by measuring cytokine expression and cellular responses.

Tryptophan metabolism primarily contributed to the formation of honey in both A. cerana and A. mellifera. A. cerana preferentially metabolized tryptophan via the indoleacetic acid pathway, yielding higher concentrations of methyl indole-3-acetate (MIA), whereas A. mellifera favored the kynurenine pathway, producing elevated levels of kynurenic acid (KYNA). Both compounds enhanced intestinal barrier integrity through their antioxidant and anti-inflammatory activities, despite differing in their specific mechanisms and efficacy. MIA exhibited superior anti-inflammatory and antioxidant properties compared with KYNA, which directly correlated with the enhanced bioactivity of A. cerana honey. KYNA primarily strengthened barrier function by upregulating the expression of tight junction proteins Zonula occludens protein-1(ZO-1), claudin-1, and occludin, whereas MIA demonstrated greater efficacy in suppressing the expression of inflammatory proteins. Correlation analyses confirmed MIA and KYNA as the key drivers of the intestinal barrier–protective activities of honey. The complementary mode of action—KYNA providing structural reinforcement and MIA offering anti-inflammatory modulation—highlights the synergistic bioactivity underlying the protective properties of honey.

These findings provide a mechanistic understanding of how bee species-specific tryptophan metabolism in A. cerana and A. mellifera drives the bioactivity divergence in honey, with MIA and KYNA linked to differential antioxidant and intestinal anti-inflammatory activities.

This study was supported by the National Natural Science Foundation of China.

Original Link: https://doi.org/10.1016/j.jare.2026.03.007

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