A Lacticaseibacillus paracasei postbiotic rescues serotonergic signaling under hyperglycemic stress in Caenorhabditis elegans and is antagonised by unmetabolised folic acid

Folic acid fortification has reduced birth defects worldwide, but in populations with high blood glucose or low vitamin B12 it has been linked to worse metabolic and neurological outcomes. Here we show, in Caenorhabditis elegans, that dietary excess glucose blunts the activity of serotonergic neurons and that a salivary Lacticaseibacillus paracasei strain AV47 restores it. A cell-free lysate (CFL) of the same organism, a postbiotic, reproduces the effect, which localises the activity to a soluble secreted fraction. The defined one-carbon cofactor 10-formyl-tetrahydrofolate reproduces the rescue, whereas the synthetic vitamer unmetabolised folic acid (UMFA) blocks it specifically under glucose stress. This conditional, combined glucose-UMFA antagonism is the central mechanistic finding, and is consistent with competition for folate receptors. The postbiotic also preserved NSM neurite length, reduced intrauterine hatching while acutely stimulating egg-laying, shifted intestinal carbon flux from storage towards utilisation, and conferred an approximately seven-fold survival advantage under acute oxidative stress together with increased locomotion. We interpret these broader outcomes as the same diet effect propagating to downstream physiology rather than as independent mechanisms. Our results describe a defined microbial cofactor activity that opposes folate-aggravated glucose toxicity in this model, and suggest that 10-formyl-tetrahydrofolate is a plausible upstream effector worth testing in mammalian systems.