Bifidobacteria with indole-3-lactic acid-producing capacity exhibit psychobiotic potential via reducing neuroinflammation

作者：Xin Qian, Qing Li, Huiyue Zhu, Ying Chen, Guopeng Lin, Hao Zhang, Wei Chen, Gang Wang, Peijun Tian · 发表于：Cell Reports Medicine · 年份：2024 · DOI：10.1016/j.xcrm.2024.101798 · 被引用次数：106 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol、Gut microbiota and health

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. • ILA-producing capacity distinguishes bifidobacteria with antidepressant effects • Aldh is essential for bifidobacteria’s ILA synthesis and antidepressant efficacy • ILA’s antidepressant effects linked to AhR-mediated neuroinflammation reli...