Microbiota-responsive BmMBF2-11 limits dysbiosis and promotes intestinal immune homeostasis in the silkworm

Intestinal microbiota are essential for insect nutrition and immunity, but how lepidopteran hosts sense and buffer microbial fluctuations remains poorly understood. Here we identify BmMBF2-11, a midgut-enriched multiprotein bridging factor 2 (MBF2) family protein in Bombyx mori, as a microbe-responsive factor that maintains gut homeostasis. RNA-seq of larval midguts from mulberry-fed (MF), artificial-diet-fed (AF), and Enterococcus mundtii-supplemented AF (AFE) groups, together with tissue expression analyses by qPCR, demonstrate that BmMBF2-11 is strongly induced by artificial-diet-associated dysbiosis and oral challenge with several opportunistic bacteria, and that its expression positively tracks intestinal bacterial burden. Using CRISPR/Cas9-mediated knockout and midgut-specific overexpression lines, together with 16S rRNA gene sequencing and infection assays, we demonstrate that BmMBF2-11 limits total bacterial load, preserves α-diversity and community structure under both mulberry and artificial-diet conditions, and promotes the inducible expression of multiple antimicrobial peptide genes in response to E. mundtii and Staphylococcus sciuri. Loss of BmMBF2-11 accelerates the expansion of E. mundtii, impairs bacterial clearance, and reduces host survival after oral infection. Our findings identify BmMBF2-11 as an MBF2-domain protein that converts microbial perturbations into appropriately scaled antibacterial responses, thereby contributing to the maintenance of gut microbiota homeostasis in Bombyx mori.