Gut metabolite indole-3-acetic acid aggravates neuropsychiatric lupus via the AHR/STAT3 pathway in microglia.

ABSTRACT: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication of systemic lupus erythematosus (SLE). Despite its high morbidity, the exact pathogenesis of NPSLE remains poorly understood, and effective therapeutic options remain unavailable. Here we show gut bacterium Lactobacillus reuteri (L. reuteri) and its metabolite indole-3-acetic acid (IAA) play key roles in the progression of NPSLE. L. reuteri and IAA induce behavioral deficits, microglial activation, pro-inflammatory cytokine secretion, neuronal loss, and blood brain barrier (BBB) disruption in female lupus-prone mice. Mechanistic studies show that IAA activates the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 3 (STAT3) signaling pathways in microglia, thereby upregulating i

SUBMITTER: Feng Y 

PROVIDER: S-EPMC12920695 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature