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Elevations of orotate (orotic acid) are consistent with enzymatic deficiencies in this pathway or urea cycle deficiencies such as a defect in ornithine transcarbamoylase

97 , E1139-1149

This microbial shift disrupts multiple gutbrain pathways simultaneously: these shifts coincided with gut barrier disruption (elevated serum endotoxin), triggering elevated hippocampal cytokines (IL-6, TNF-), which in turn suppress Tph2 expression and induce Tph2 hypermethylation (suggesting neuroinflammation and serotonergic suppression), ultimately manifesting as anxiety and depression-like behaviors (Buchenauer et al., 2023)

Sies, H