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A colitis model was induced in rats with 2, 4, 6\u2010trinitrohydrosulfonic acid (TNBS), followed by ST36 and SP6 targeted therapy by EA or sham EA treatment. The elevated plus maze (EPM) and open\u2010field test (OFT) were performed to assess the state of anxiety and depression\u2010like behavior. Tests were carried out by 16S rDNA amplification sequence, <jats:sup>1<\/jats:sup>H nuclear magnetic resonance (<jats:sup>1<\/jats:sup>H NMR) spectroscopy, immunofluorescence staining, and enzyme\u2010linked immunosorbent assay (ELISA). The analyses detailed metabolic alterations and the Toll\u2010like receptor 4 (TLR4) signaling pathway\/NOD\u2010like receptor protein 3 (NLRP3) inflammasome in rats\u2019 hippocampal region. Furthermore, the activity of the hypothalamic\u2010pituitary adrenal (HPA) axis and gut microbiome was assessed. As a result of treatment, EA significantly improved in the behavioral tests and altered the composition of the gut microbiome through a significant increase in the density of short chain fatty acids (SCFAs) producers mainly including <jats:italic>Ruminococcaceae<\/jats:italic>, <jats:italic>Phascolarctobacterium<\/jats:italic>, and <jats:italic>Akkermansiaceae<\/jats:italic>. EA upregulated the metabolites of the hippocampus mainly containing l\u2010glutamine and gamma\u2010aminobutyric acid (GABA), as well as ZO\u20101 expression. Whereas the treatment blocked the TLR4\/nuclear factor\u2010 kappa B (NF\u2010<jats:italic>\u03ba<\/jats:italic>B) signaling pathways and NLRP3 inflammasomes, along with downregulating the interleukin\u2010 (IL\u2010) 1<jats:italic>\u03b2<\/jats:italic> level. The hyperactivity of the HPA axis was also diminished. In conclusion, EA at ST36 and SP6 attenuated anxiety and depression\u2010like behavior in colitis model rats through their effects on the gut microbiome by modulating the hippocampal inflammatory response and metabolic disorders, as well as the HPA axis. This study provides evidence for clinical application of EA to serve as an adjunctive treatment for IBD\u2010related anxiety and depression.<\/jats:p>","DOI":"10.1155\/2022\/8295580","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:50:07Z","timestamp":1642553407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Electroacupuncture Attenuated Anxiety and Depression\u2010Like Behavior via Inhibition of Hippocampal Inflammatory Response and Metabolic Disorders in TNBS\u2010Induced IBD 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