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<p>Neuropsychiatric systemic&#xa0;lupus erythematosus&#xa0;(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 <i>Lactobacillus reuteri</i> (<i>L. reuteri</i>) and its metabolite indole-3-acetic acid (IAA) play key roles in the progression of NPSLE. <i>L. reuteri</i> 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 inflammatory responses and exacerbating neuroinflammation. These findings suggest a critical role for gut-microbiota-metabolite-brain axis in NPSLE pathogenesis and provide insights into potential therapeutic targets.</p><p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月23日

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  • Yi Feng,
  • Lijuan Zheng,
  • Wenli Tang,
  • Pan Wang,
  • Yanxia Lai,
  • Jiayu Qin,
  • Chang Zhou,
  • Xian Zhang,
  • Min Yang,
  • Ligang Jie,
  • Guangchuang Yu,
  • Hao Ren,
  • Qin Huang

摘要

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 inflammatory responses and exacerbating neuroinflammation. These findings suggest a critical role for gut-microbiota-metabolite-brain axis in NPSLE pathogenesis and provide insights into potential therapeutic targets.