ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1640149
This article is part of the Research TopicRodent Model Organisms: Therapeutic Treatments and Drugs Interaction with the Gut Microbiome, Volume IIView all 3 articles
The gut commensal Faecalibacterium hominis attenuates indole -AhR signaling and restores ASD -like behaviors with BTBR mice
Provisionally accepted
You Yu1*
Yujing Wang2
Jie Zhang3Shucheng Li4
Yulin Wang4
You Xin5
Chen Xue3Mengxuan Du4Lisheng Xie3
Shuang-Jiang Liu3*- 1Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China
- 2Institute of Process Engineering Chinese Academy of Sciences, Beijing, China
- 3Institute of Microbiology Chinese Academy of Sciences, Beijing, China
- 4Shandong University - Qingdao Campus, Qingdao, China
- 5Peking Union Medical College Hospital, Beijing, China
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Autism spectrum disorders (ASD), a group of neurodevelopmental disorders characterized by the core symptoms of impaired social communication and stereotyped behaviors, is strongly associated with dysregulated microbiota-gut-brain axis.Emerging evidence suggests that Faecalibacterium, which showed reduced abundance in ASD cohorts, holds therapeutic potential, though its interaction with host remain unexplored. Here, we investigated the efficacy and molecular basis of Faecalibacterium hominis 4P-15 (4P-15) in BTBR T + Itpr3 tf /J (BTBR) mice, an idiopathic ASD mouse model. Oral administration of 4P-15 significantly reduced the intestinal levels of indole, indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA), as well as the level of IPA in brain. Furthermore, the decreased levels of IPA in brain contributed to the attenuated aryl hydrocarbon receptor (AhR) signaling characterized by increased expression of downstream elements, including glutamate transporters and GABA receptors. Ultimately, this modulation led to the restoration of excitatory/inhibitory imbalance, a typical pathophysiological feature of ASD, and thereby alleviated ASD core behavioral symptoms. Our findings underscore Faecalibacterium-mediated AhR modulation as a promising therapeutic strategy for ASD, highlighting the dual potential of Faecalibacterium-based probiotics and targeted interventions against indole-AhR signaling to address neurodevelopmental disorders.
Keywords: the gut-brain axis, Autism spectrum disorders (ASD), microbiome, indole, Aryl hydrocarbon receptor (AhR), BTBR
Received: 03 Jun 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Yu, Wang, Zhang, Li, Wang, Xin, Xue, Du, Xie and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
You Yu, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China
Shuang-Jiang Liu, Institute of Microbiology Chinese Academy of Sciences, Beijing, China
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