The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR mice
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 r...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1640149/full |
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| author | You Yu Yujing Wang Yujing Wang Jie Zhang Shucheng Li Yulin Wang Xin You Xue Chen Mengxuan Du Lisheng Xie Shuang-Jiang Liu Shuang-Jiang Liu |
| author_facet | You Yu Yujing Wang Yujing Wang Jie Zhang Shucheng Li Yulin Wang Xin You Xue Chen Mengxuan Du Lisheng Xie Shuang-Jiang Liu Shuang-Jiang Liu |
| author_sort | You Yu |
| collection | DOAJ |
| description | 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+Itpr3tf/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. |
| format | Article |
| id | doaj-art-4a1c3e4506cc4d26959af694100c46f9 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-4a1c3e4506cc4d26959af694100c46f92025-08-22T05:26:45ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-08-011610.3389/fmicb.2025.16401491640149The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR miceYou Yu0Yujing Wang1Yujing Wang2Jie Zhang3Shucheng Li4Yulin Wang5Xin You6Xue Chen7Mengxuan Du8Lisheng Xie9Shuang-Jiang Liu10Shuang-Jiang Liu11State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medica Sciences & Peking Union Medical College, Beijing, ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao, ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao, ChinaAutism 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+Itpr3tf/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.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1640149/fullthe gut-brain axisautism spectrum disorders (ASD)microbiomeindolearyl hydrocarbon receptor (AhR)BTBR |
| spellingShingle | You Yu Yujing Wang Yujing Wang Jie Zhang Shucheng Li Yulin Wang Xin You Xue Chen Mengxuan Du Lisheng Xie Shuang-Jiang Liu Shuang-Jiang Liu The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR mice Frontiers in Microbiology the gut-brain axis autism spectrum disorders (ASD) microbiome indole aryl hydrocarbon receptor (AhR) BTBR |
| title | The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR mice |
| title_full | The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR mice |
| title_fullStr | The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR mice |
| title_full_unstemmed | The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR mice |
| title_short | The gut commensal Faecalibacterium hominis attenuates indole—AhR signaling and restores ASD—like behaviors with BTBR mice |
| title_sort | gut commensal faecalibacterium hominis attenuates indole ahr signaling and restores asd like behaviors with btbr mice |
| topic | the gut-brain axis autism spectrum disorders (ASD) microbiome indole aryl hydrocarbon receptor (AhR) BTBR |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1640149/full |
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