Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila
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
Affiliations
Miaomiao Pan
MOE/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, China
Chenglang Qian
MOE/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, China
Shaoye Huo
Department of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
Yuchen Wu
Institute of Wound Prevention and Treatment, Shanghai University of Medicine & Health Sciences, Shanghai, China
Xinyi Zhao
Vanke School Pudong, Shanghai, China
Yueming Ying
University College London, London, UK
Boyu Wang
MOE/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, China
Hao Yang
MOE/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, China
Anaguli Yeerken
MOE/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, China
Tongyao Wang
MOE/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, China
Mengwei Fu
MOE/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, China
Lihong Wang
Department of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
Yuhuan Wei
Department of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
Yunhua Zhao
Department of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
Chunhai Shao
Department of Clinical Nutrition, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
Huijing Wang
Institute of Wound Prevention and Treatment, Shanghai University of Medicine & Health Sciences, Shanghai, China
Chao Zhao
MOE/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, China
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.
