{"title":"Bifidobacteria with indole-3-lactic acid-producing capacity exhibit psychobiotic potential via reducing neuroinflammation.","authors":"Xin Qian, Qing Li, Huiyue Zhu, Ying Chen, Guopeng Lin, Hao Zhang, Wei Chen, Gang Wang, Peijun Tian","doi":"10.1016/j.xcrm.2024.101798","DOIUrl":null,"url":null,"abstract":"<p><p>The escalating global prevalence of depression demands effective therapeutic strategies, with psychobiotics emerging as a promising solution. However, the molecular mechanisms governing the neurobehavioral impact of psychobiotics remain elusive. This study reveals a significant reduction in hippocampal indole-3-lactic acid (ILA) levels in depressed mice, which is ameliorated by the psychobiotic Bifidobacterium breve. In both human subjects and mice, the ILA increase in the circulatory system results from bifidobacteria supplementation. Further investigation identifies the key aromatic lactate dehydrogenase (Aldh) gene and pathway in bifidobacteria responsible for ILA production. Importantly, the antidepressant effects are nullified in the Aldh mutants compared to the wild-type strain. At the bifidobacteria species level, those with Aldh exhibit heightened antidepressant effects. Finally, this study emphasizes the antidepressant efficacy of psychobiotic-derived ILA, potentially mediated by aryl hydrocarbon receptor (AhR) signaling activation to alleviate neuroinflammation. This study unveils the molecular and genetic foundations of psychobiotics' antidepressant effects, offering insights for microbial therapies targeting mood disorders.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xcrm.2024.101798","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The escalating global prevalence of depression demands effective therapeutic strategies, with psychobiotics emerging as a promising solution. However, the molecular mechanisms governing the neurobehavioral impact of psychobiotics remain elusive. This study reveals a significant reduction in hippocampal indole-3-lactic acid (ILA) levels in depressed mice, which is ameliorated by the psychobiotic Bifidobacterium breve. In both human subjects and mice, the ILA increase in the circulatory system results from bifidobacteria supplementation. Further investigation identifies the key aromatic lactate dehydrogenase (Aldh) gene and pathway in bifidobacteria responsible for ILA production. Importantly, the antidepressant effects are nullified in the Aldh mutants compared to the wild-type strain. At the bifidobacteria species level, those with Aldh exhibit heightened antidepressant effects. Finally, this study emphasizes the antidepressant efficacy of psychobiotic-derived ILA, potentially mediated by aryl hydrocarbon receptor (AhR) signaling activation to alleviate neuroinflammation. This study unveils the molecular and genetic foundations of psychobiotics' antidepressant effects, offering insights for microbial therapies targeting mood disorders.
全球抑郁症发病率不断攀升,需要有效的治疗策略,而精神生物制剂则是一种很有前景的解决方案。然而,精神类药物对神经行为影响的分子机制仍然难以捉摸。这项研究揭示了抑郁小鼠海马吲哚-3-乳酸(ILA)水平的显著下降,而精神生物双歧杆菌(Bifidobacterium breve)能改善这种情况。在人类受试者和小鼠中,循环系统中吲哚-3-乳酸的增加都是由于补充了双歧杆菌。进一步的研究确定了双歧杆菌中负责产生 ILA 的关键芳香族乳酸脱氢酶(Aldh)基因和途径。重要的是,与野生型菌株相比,Aldh突变体的抗抑郁效果无效。在双歧杆菌物种水平上,含有 Aldh 的双歧杆菌表现出更强的抗抑郁作用。最后,本研究强调了精神生物源 ILA 的抗抑郁功效,它可能通过芳基烃受体(AhR)信号激活来缓解神经炎症。本研究揭示了精神生物抗抑郁作用的分子和遗传基础,为针对情绪障碍的微生物疗法提供了启示。
Cell Reports MedicineBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍:
Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine.
Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.