Gut microbiome and host TOR pathway interact to regulate predator-induced aversive memory in Drosophila melanogaster
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
122
Journal Issue
25
Start Page
e2422928122
ISSN
1091-6490
Date Issued
2025-06-24
Author(s)
Chen, Hao-Yu
Wu, Po-Sheng
Li, Zong-You
Liu, You-Cheng
Yeh, Sheng-Rong
Duan, Bi-Chun
Cheng, Kai-Wen
Chiu, Yen-Ling
Abstract
The gut microbiome has emerged as a key factor influencing a wide range of host physiological processes and behaviors, though the mechanisms behind these effects remain only partially understood. In this study, we explored the role of the gut microbiome in memory regulation using a parasitoid wasp-induced oviposition depression paradigm in . Our findings show that flies with depleted gut microbiota, either through axenic culture or antibiotic treatment, exhibited significant memory impairments. However, reintroducing the commensal bacterium alone was sufficient to restore memory, while coinoculation with further enhanced memory performance. Hemolymph metabolomic analyses revealed reduced amino acid levels in antibiotic-treated flies, which were linked to impaired target of rapamycin (dTOR) signaling. Additionally, genetic manipulation of dTOR or dietary supplementation with branched-chain amino acids either mimicked or rescued the memory deficits caused by antibiotic treatments. These results suggest that the gut microbiome is essential for regulating memory function by maintaining amino acid homeostasis and proper dTOR signaling, with profound implications for advancing knowledge of cognitive regulation.
Subjects
TOR
gut microbiome
memory
Publisher
National Academy of Sciences
Type
journal article