Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila
The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as a key med...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2447834 |
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| author | Miaomiao Pan Chenglang Qian Shaoye Huo Yuchen Wu Xinyi Zhao Yueming Ying Boyu Wang Hao Yang Anaguli Yeerken Tongyao Wang Mengwei Fu Lihong Wang Yuhuan Wei Yunhua Zhao Chunhai Shao Huijing Wang Chao Zhao |
| author_facet | Miaomiao Pan Chenglang Qian Shaoye Huo Yuchen Wu Xinyi Zhao Yueming Ying Boyu Wang Hao Yang Anaguli Yeerken Tongyao Wang Mengwei Fu Lihong Wang Yuhuan Wei Yunhua Zhao Chunhai Shao Huijing Wang Chao Zhao |
| author_sort | Miaomiao Pan |
| collection | DOAJ |
| description | The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as a key mediator. However, it remains unclear whether specific microbial factors regulate tryptophan metabolism to influence 5-HT production and anxiety regulation. In this study, we analyzed 110 athletes undergoing closed training and found that fecal lactate levels were significantly associated with anxiety indicators. We observed a significant negative correlation between Akkermansia abundance and anxiety levels in athletes. Co-supplementation with lactate and Akkermansia muciniphila (A. muciniphila) modulated tryptophan metabolism by increasing key enzyme TPH1 and reducing IDO1, thus shifting metabolism from kynurenine (Kyn) to 5-HT. In addition, lactate enhanced the propionate production capacity of A. muciniphila, potentially contributing to anxiety reduction in mice. Taken together, these findings suggest that enteric lactate and A. muciniphila collaboratively restore the imbalance in tryptophan metabolism, leading to increased 5-HT activity and alleviating anxiety phenotypes. This study highlights the intricate interplay between gut metabolites and anxiety regulation, offering potential avenues for microbiota-targeted therapeutic strategies for anxiety. |
| format | Article |
| id | doaj-art-d430c223df1b4b868e5eebe3f7990515 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-d430c223df1b4b868e5eebe3f79905152025-01-09T10:20:42ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2024.2447834Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphilaMiaomiao Pan0Chenglang Qian1Shaoye Huo2Yuchen Wu3Xinyi Zhao4Yueming Ying5Boyu Wang6Hao Yang7Anaguli Yeerken8Tongyao Wang9Mengwei Fu10Lihong Wang11Yuhuan Wei12Yunhua Zhao13Chunhai Shao14Huijing Wang15Chao Zhao16MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaMOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaInstitute of Wound Prevention and Treatment, Shanghai University of Medicine & Health Sciences, Shanghai, ChinaVanke School Pudong, Shanghai, ChinaUniversity College London, London, UKMOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaMOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaMOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaMOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaMOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaDepartment of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaDepartment of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaDepartment of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, ChinaInstitute of Wound Prevention and Treatment, Shanghai University of Medicine & Health Sciences, Shanghai, ChinaMOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaThe gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as a key mediator. However, it remains unclear whether specific microbial factors regulate tryptophan metabolism to influence 5-HT production and anxiety regulation. In this study, we analyzed 110 athletes undergoing closed training and found that fecal lactate levels were significantly associated with anxiety indicators. We observed a significant negative correlation between Akkermansia abundance and anxiety levels in athletes. Co-supplementation with lactate and Akkermansia muciniphila (A. muciniphila) modulated tryptophan metabolism by increasing key enzyme TPH1 and reducing IDO1, thus shifting metabolism from kynurenine (Kyn) to 5-HT. In addition, lactate enhanced the propionate production capacity of A. muciniphila, potentially contributing to anxiety reduction in mice. Taken together, these findings suggest that enteric lactate and A. muciniphila collaboratively restore the imbalance in tryptophan metabolism, leading to increased 5-HT activity and alleviating anxiety phenotypes. This study highlights the intricate interplay between gut metabolites and anxiety regulation, offering potential avenues for microbiota-targeted therapeutic strategies for anxiety.https://www.tandfonline.com/doi/10.1080/19490976.2024.2447834Gut microbiome5-hydroxytryptaminecompetitive anxietytryptophanlactic acidAkkermansia muciniphila |
| spellingShingle | Miaomiao Pan Chenglang Qian Shaoye Huo Yuchen Wu Xinyi Zhao Yueming Ying Boyu Wang Hao Yang Anaguli Yeerken Tongyao Wang Mengwei Fu Lihong Wang Yuhuan Wei Yunhua Zhao Chunhai Shao Huijing Wang Chao Zhao Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila Gut Microbes Gut microbiome 5-hydroxytryptamine competitive anxiety tryptophan lactic acid Akkermansia muciniphila |
| title | Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila |
| title_full | Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila |
| title_fullStr | Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila |
| title_full_unstemmed | Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila |
| title_short | Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila |
| title_sort | gut derived lactic acid enhances tryptophan to 5 hydroxytryptamine in regulation of anxiety via akkermansia muciniphila |
| topic | Gut microbiome 5-hydroxytryptamine competitive anxiety tryptophan lactic acid Akkermansia muciniphila |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2447834 |
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