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

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. • 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 relief Qian et al. reveal that psychobiotic Bifidobacterium breve reverses the abnormal reduction of hippocampal indole-3-lactic acid (ILA) in depressed mice. The study highlights the role of Aldh gene in ILA production by bifidobacteria and its antidepressant effects through AhR signaling, advancing the understanding of psychobiotics in mood disorder therapies.

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