RT Journal A1 Duan, Yuange A1 Huang, Min A1 Ye, Lin A1 Ma, Ling A1 Wu, Yashuai A1 Du, Yating A1 Liu, Jiyao A1 Song, Fan A1 Tian, Li A1 Cai, Wanzhi A1 Li, Hu A1 Zhou, Xin A1 Luo, Shiqi T1 Dynamic A-to-I RNA editing in response to gut microbiome in honeybees JF Genome Research JO Genome Research YR 2026 FD March 04 DO 10.1101/gr.280291.124 UL http://genome.cshlp.org/content/early/2026/03/18/gr.280291.124.abstract AB ADAR-mediated adenosine-to-inosine (A-to-I) mRNA editing contributes to the proteomic diversity and behavioral complexity of animals. Although recent studies indicate that the gut microbiome influences various aspects of animal behavior, the potential involvement of RNA editing in gut–brain interactions remains unexplored. Here, we perform comparative transcriptomic analyses between heads of germ-free (GF) versus conventional (CV) honeybees. A total of 1528 A-to-I editing sites are identified in honeybee heads, among which nonsynonymous editing sites are overrepresented compared with random expectation. Overall editing levels are significantly downregulated in GF compared with CV, but the Adar gene is not differentially expressed. However, the Adar p.482 Ile > Met auto-recoding site, which is speculated to modulate Adar activity, is identified as a high-confidence differential editing site (DES) with decreased editing level in GF. Quantification of gut microbiota across 12 CV individuals reveals a significant positive correlation between p.482 Ile > Met editing level and Lactobacillus and Bombilactobacillus abundance. Colonization of a single bacterium Lactobacillus or Bombilactobacillus instead of Gilliamella in GF bees successfully restores the Adar p.482 Ile > Met and the global editing level. Our work demonstrates the complex and dynamic transcriptomic diversity exerted by A-to-I RNA editing and discovers the axis of gut–Lactobacillus/Bombilactobacillus–brain–Adar–global RNA editing, providing an exciting scenario that gut microbiomes could impact RNA editing, which might further facilitate phenotypic plasticity of social insects.