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

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

  • Commun Biol. 2026 Jan 23;9(1):281. doi: 10.1038/s42003-026-09561-7.
Yi Feng # 1 2,  Lijuan Zheng # 1 3,  Wenli Tang # 4,  Pan Wang 1,  Yanxia Lai 1,  Jiayu Qin 1,  Chang Zhou 5,  Xian Zhang 6,  Min Yang 1,  Ligang Jie 7,  Guangchuang Yu 8,  Hao Ren 9,  Qin Huang 10
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Department of Rheumatology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • 3 Intensive Care Unit, Department of Emergency Medicine, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, China.
  • 4 Ningbo Key Laboratory of Human Microbiome and Precision Medicine, Central Laboratory of the Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, China.
  • 5 Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 6 School of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • 7 Department of Rheumatology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. [email protected].
  • 8 Department of Bioinformatics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. [email protected].
  • 9 Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China. [email protected].
  • 10 Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, China. [email protected].
  • # Contributed equally.
PMID: 41577835 DOI: 10.1038/s42003-026-09561-7
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 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.

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