Abstract

Nutrients sources are directly related to the development and behavior of all living organisms. Understanding the mechanisms by which dietary molecules interact with intestinal and neuronal functions is a new approach to describe the development of neurodegenerative diseases and behavior illness. In our laboratory, we discovered that when the nematode bacterivore C. elegans, mec-4d mutant, were fed with E. coli K12 HT115 neuronal death was prevented by 50%, compared to E. coli B OP50 diet. This animal model mec-4d is based on a constantly opened sodium channel that promotes axonal damage of touch response neurons in a trackable manner. In this study, we described the neuroprotective effect provided by a bacterial diet and identified the responsible metabolites. First, we predicted compounds by differential metabolic pathways among both bacteria strains using genomic and transcriptomic analysis, and secondly, we validated with bacteria mutants, pharmacological supplementation, and metabolomic analysis. We found that E. coli HT115 overexpressed 60 genes absent in E. coli B OP50, including glutamate decarboxylase (gadA, gadB), which produced gamma-aminobutyric acid from L-glutamic acid. When mec-4d worms were fed with E. coli HT115 mutants for GABA production the neuroprotective effect was diminished by 40% (p=0.0001). Moreover, wild-type axons were recovered in 30% in mec-4d worms by dietary GABA supplementation (p=0.04) or genetic complementation of gadA (p=0.018). According to those results, we proposed the role of dietary E. coli GABA producing bacteria in the neuroprotection process, including its accessibility through the intestine and activation of molecular signaling to prevent axonal damage.