# Free and Easy Wanderer Ameliorates Intestinal Bloating‐Dependent Avoidance Behavior of Caenorhabditis elegans Through Gut‐Germline‐Neural Signaling

## TL;DR

This study shows that Free and Easy Wanderer (FAEW) reduces avoidance behavior in C. elegans by affecting gut-germline-neural signaling and H4K8ac protein levels.

## Contribution

FAEW's protective effect on avoidance behavior is demonstrated through gut-germline-neural signaling and DAF-16 activation in C. elegans.

## Key findings

- FAEW delays avoidance behavior and reduces intestinal bloating in C. elegans.
- FAEW decreases H4K8ac and par-5 levels in the germline and activates DAF-16.
- The effect of FAEW is lost in daf-16 mutants but restored in rescued animals.

## Abstract

The aim of this study was to investigate the protective effect of Free and Easy Wanderer (FAEW) on the avoidance behavior induced by feeding Heat‐Killed
Escherichia coli
, and to elucidate the underlying mechanisms.

Initially, the effects of FAEW on avoidance behavior, survival, neuroendocrine signaling gene expression, and intestinal bloating were examined. The impact of FAEW on gut‐germline‐neural signaling was assessed by monitoring H4K8ac expression and the avoidance behavior of par‐5 RNAi animals and glp‐1(e2141) mutants. RNA‐sequencing was conducted to analyze potential signaling pathways. Finally, avoidance behavior was examined using daf‐16(mu86) mutants and the rescued animals.

FAEW delayed avoidance behavior. FAEW significantly downregulated gene expression in the neuroendocrine signaling pathway and alleviated intestinal bloating of
C. elegans
. The levels of H4K8ac and par‐5 in the germline decreased significantly with FAEW's treatment, and FAEW failed to affect the avoidance behavior of par‐5 RNAi animals and glp‐1(e2141) mutants. FAEW's effect on avoidance behavior diminished in daf‐16(mu86) mutants but was restored in daf‐16 rescued animals. FAEW has been observed to restore daf‐16 levels.

FAEW protects against avoidance behavior of
C. elegans
through downregulating H4K8ac protein expression and activating DAF‐16. This study provides crucial experimental evidence supporting FAEW as a promising candidate for protecting against avoidance behavior associated with PTSD.

Using
C. elegans
as a model organism, we scrutinized the effects of FAEW on pathogen avoidance behaviors via the gut‐germline‐neural signaling. Demonstrating for the first time that FAEW prevents avoidance behavior through gut‐germline‐neural signaling, inhibition of H4K8 acetylation, and activation of DAF‐16.