Abstract

Organisms coexist in symbiosis with bacterial consortia, especially in intestinal tracts for nutrients decomposition and metabolite turnover. The role of the microbiome on phenotype and behavior had been shown in several animal models. However, the identity of bacterial molecules promoting changes in hosts and how intestine-neuron communication occurs is poorly understood. We studied the influence of bacterial diets in a C. elegans model of progressive neurodegeneration. These animals express a neurotoxic allele of the MEC-4(d) DEG/ENaC channel of the touch receptor neurons (TRN, Driscoll and Chalfie, 1991). Several laboratory (E. coli, P. aerouginosa, B. megaterium, Comamonas sp.), and environmental (P. kiredjianiae, S. humi, and B. pumilus) bacterial strains were analyzed in their ability to reduce neurodegeneration adulthood. We determined that dietary beneficial effect is triggered prior 12 hours after hatching and is not heritable. By omics analysis and biochemical validation, we demonstrated that differential gamma-aminobutyric acid production between E. coli OP50 and E. coli HT115 is positively correlated with neuroprotection. Using reverse genetics we show that GABA transporters (snf-5, snf-11, unc-47), channels (unc-49) and receptors (lgc-37, gab-1) are required systemically and not TRN-autonomously for protection. We further showed that DAF-16 is required for bacterially induced neuroprotection to take place. Additionally, DAF-16/FOXO is translocated to the nuclei in animals feeding on neuroprotective bacteria at 24 hours after hatching. Together, these results demonstrate that bacterially produced GABA exerts an effect of neuroprotection in the host, highlighting the role of neuroactive compounds of the diet in nervous system homeostasis.