# Microbial Lipopolysaccharide Regulates Host Development Through Insulin/IGF-1 Signaling

## TL;DR

This study shows that bacterial LPS can delay worm development by affecting insulin signaling, suggesting a new role for microbes in host development.

## Contribution

The study reveals a novel role for microbial LPS in regulating host development via insulin/IGF-1 signaling.

## Key findings

- Loss of outer core glycosylation in ∆rfaG mutant LPS causes developmental delay in C. elegans.
- Developmental delay is rescued by exogenous LPS or amino acid supplementation.
- LPS-induced developmental arrest is mediated by the host FOXO transcription factor DAF-16.

## Abstract

Lipopolysaccharide (LPS), the defining outer membrane component of Gram-negative bacteria, is a potent immunostimulant recognized by Toll-like receptor 4 (TLR4). While extensively studied for its roles in immune activation and barrier disruption, the potential function of LPS as a developmental cue remains largely unexplored. By leveraging Caenorhabditis elegans and its genetic and gnotobiotic advantages, we screened a panel of Escherichia coli LPS biosynthesis mutants. This screen revealed that the loss of outer core glycosylation in the ∆rfaG mutant causes significant developmental delay independent of bacterial metabolism. Animals exhibited developmental delay that was rescued by exogenous LPS or amino acid supplementation, implicating that LPS triggers nutrient-sensing signaling. Mechanistically, this developmental arrest was mediated by the host FOXO transcription factor DAF-16, which is the key effector of insulin/IGF-1 signaling (IIS). Our findings uncover an unprecedented role for microbial LPS as a critical regulator of host development, mediated through conserved host IIS pathways, fundamentally expanding our understanding of host–microbe crosstalk.