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

## TL;DR

Gut bacteria in fruit flies boost reproduction by producing a compound that helps regulate key proteins involved in reproduction.

## Contribution

The study reveals a novel mechanism by which gut bacteria regulate host reproduction through nicotinic acid and the Lolal-dpp axis.

## Key findings

- Gut bacteria produce nicotinic acid, which enhances energy metabolism and promotes degradation of the Lolal protein.
- Lolal overabundance in bacteria-depleted flies causes reproductive defects by overexpressing dpp.
- Lolal knockdown disrupts egg formation, showing its critical role in reproduction.

## Abstract

Gut commensal microbiota can play an integral role in shaping insect reproduction, but the underlying mechanisms remain largely unexplored. Here, we report that gut bacteria promote host reproduction in the oriental fruit fly Bactrocera dorsalis by inducing ubiquitin–proteasome system (UPS)-mediated degradation of the key transcription factor Longitudinals lacking-like (Lolal). Antibiotic-induced gut bacterial depletion impairs ovarian development and fertility. These reproductive defects can be reversed by nicotinic acid (NA) supplementation or recolonization with a potent NA provider, Enterobacter hormaechei. Gut bacteria-derived NA enhances coenzyme nicotinamide adenine dinucleotide (NAD) biosynthesis and mitochondrial energy production, thereby activating the UPS. Ubiquitinome analysis reveals that gut bacteria enhance Lolal ubiquitination and promote its degradation. Lolal overabundance in gut bacteria-depleted females leads to decapentaplegic (dpp) overexpression and impaired reproduction. Conversely, Lolal knockdown suppresses dpp expression, resulting in disrupted mature egg formation. Our results reveal a link between gut bacteria-derived metabolites and host protein homeostasis which determines host reproductive success.

Here, the authors show that gut bacteria promote reproduction in the oriental fruit fly by producing nicotinic acid that regulates energy metabolism and Lolal-dpp homeostasis.