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

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: free and easy wanderer; H4K8ac; gut‐germline‐neural signaling; intestinal bloating.