Bifidobacterium animalis subsp. lactis BD1 restores neurotransmitter homeostasis in chronically stressed mice via tryptophan metabolic reprogramming

Background: Chronic psychological stress is a major precipitating factor for neuropsychiatric disorders, yet the underlying mechanisms remain incompletely understood. The gut-brain axis has emerged as a critical regulator of mood and behavior, but how specific commensal microbes modulate host neurochemistry to confer stress resilience is largely unknown. In this study, we aimed to demonstrate that the probiotic strain Bifidobacterium animalis subsp. lactis BD1 alleviates depression-like behaviors in mice and to further elucidate the underlying mechanisms.
Results: We found that chronic restraint stress in mice induced gut dysbiosis, anxiety- and depressive-like behaviors, which were associated with impaired colonic synthesis of 5-hydroxytryptophan (5-HTP), the direct precursor to serotonin. This intestinal metabolic disturbance led to depleted systemic and central serotonin levels and reduced hippocampal brain-derived neurotrophic factor (BDNF). Notably, B. animalis BD1 supplementation restored the populations of beneficial Bifidobacterium and Lactobacillus, significantly enhanced colonic 5-HTP production, and consequently normalized brain serotonin and BDNF expression. These neurochemical improvements were functionally correlated with enhanced synaptic plasticity and attenuated microglial activation, ultimately reversing the behavioral deficits.
Conclusion: our findings identify a key mechanism whereby B. animalis BD1 modulates host tryptophan metabolism at the gut level to buffer the neurobehavioral consequences of chronic stress, highlighting the therapeutic potential of precision probiotics for managing stress-related psychiatric conditions.