Frontiers in Cellular and Infection Microbiology (Apr 2024)

High-fat diets induce inflammatory IMD/NFκB signaling via gut microbiota remodeling in Drosophila

  • Jun Wang,
  • Jiaojiao Gu,
  • Jianhan Yi,
  • Jie Li,
  • Wen Li,
  • Zongzhao Zhai

DOI
https://doi.org/10.3389/fcimb.2024.1347716
Journal volume & issue
Vol. 14

Abstract

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High-fat diets (HFDs), a prevailing daily dietary style worldwide, induce chronic low-grade inflammation in the central nervous system and peripheral tissues, promoting a variety of diseases including pathologies associated with neuroinflammation. However, the mechanisms linking HFDs to inflammation are not entirely clear. Here, using a Drosophila HFD model, we explored the mechanism of HFD-induced inflammation in remote tissues. We found that HFDs activated the IMD/NFκB immune pathway in the head through remodeling of the commensal gut bacteria. Removal of gut microbiota abolished such HFD-induced remote inflammatory response. Further experiments revealed that HFDs significantly increased the abundance of Acetobacter malorum in the gut, and the re-association of this bacterium was sufficient to elicit inflammatory response in remote tissues. Mechanistically, Acetobacter malorum produced a greater amount of peptidoglycan (PGN), a well-defined microbial molecular pattern that enters the circulation and remotely activates an inflammatory response. Our results thus show that HFDs trigger inflammation mediated by a bacterial molecular pattern that elicits host immune response.

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