The Lolal-dpp axis mediates the regulation of host reproduction by gut symbionts in insects

Gut commensal microbiota can play an integral role in shaping insect reproduction, but the mechanisms underlying this process remain largely unexplored. Here, we report that gut bacteria promote host reproduction in the oriental fruit fly Bactrocera dorsalis (Diptera: Tephritidae), an important agricultural pest. To do so, bacteria induce the degradation of the key transcription factor longitudinals lacking-like (Lolal) via the ubiquitin-proteasome system (UPS). Depletion of gut commensal bacteria impaired ovarian development and fertility. This reproductive defect could be reversed by nicotinic acid (NA) supplementation or recolonization with the potent NA provider Enterobacter hormaechei bacterium. Gut bacteria-derived NA promoted coenzyme NAD biosynthesis and mitochondrial energy production, which in turn activated the UPS. Ubiquitinome analysis further revealed that gut bacteria enhance Lolal ubiquitination and promote its degradation, preventing excessive Lolal accumulation. Lolal overabundance in gut bacteria-depleted females led to decapentaplegic (dpp) overexpression and impaired female reproduction. Conversely, Lolal knockdown led to decreased dpp expression resulting in the disruption of mature egg formation. Our results uncover a link between gut bacteria-derived metabolites and host protein homeostasis which determines host reproduction.