BmMBF2-11 Couples FADD-Mediated IMD Signaling to Gut Microbial Homeostasis in the Silkworm

Gut microbial imbalance is a constraint on insect health and artificial diet-based silkworm rearing, but how lepidopteran hosts convert microbial fluctuations into appropriate immune output remains unclear. In this study, we investigated the molecular mechanism by which the microbiota-responsive factor BmMBF2-11 regulates gut immune homeostasis in Bombyx mori. Transcriptomic and interactomic analyses, together with structural prediction, colocalization, Co-IP, BiFC, and GST pull-down assays, identified FADD as a direct interacting partner of BmMBF2-11. Bacterial challenge with Staphylococcus sciuri or Enterococcus mundtii showed that BmMBF2-11 was associated with the induction of FADD, Relish, and multiple antimicrobial peptide genes, whereas FADD knockdown impaired these transcriptional responses. FADD knockdown increased bacterial load, reduced microbial diversity, remodeled gut microbial composition, weakened E. mundtii clearance, and reduced host survival. These findings reveal a BmMBF2-11-FADD regulatory axis linking IMD/Relish-related immune output to gut microbial homeostasis and provide insight into silkworm health management under artificial diet-rearing conditions.