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Lactobacillus acidophilus LA3 Suppresses Neuroinflammation via the Gut-Brain Axis
Ying Chen1,2, Miaoyu Li2,3, Jiaqi Wang2
1Central Laboratory of Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's Hospital, Lishui323000, Zhejiang, China.
Abstract:
The gut-brain axis represents a pivotal pathway through which gut microbiota influence neuroinflammation and neurological health. This study identifies Lactobacillus acidophilus LA3 as a potent probiotic strain capable of mitigating neuroinflammation. LA3 demonstrated superior efficacy in suppressing LPS-induced proinflammatory cytokines in BV-2 microglia. In an LPS-induced murine model, LA3 alleviated systemic and neuroinflammation, depressive-like behaviors, and cognitive impairment, while restoring blood-brain and gut-vascular barrier integrity. LA3 reversed gut microbiota dysbiosis, enriched short-chain fatty acid-producing bacteria, and promoted indole-3-acetic acid (IAA) levels in colonic contents and brain. The anti-inflammatory effect of LA3 was AHR-dependent, as confirmed by an AHR inhibitor in BV-2 cells. Notably, both LA3 fermentation supernatant and exogenous IAA (at the same dose as detected in the supernatant) recapitulated key aspects of LA3's effects. Collectively, L. acidophilus LA3 represents a promising next-generation probiotic targeting the gut-brain axis, with IAA serving as an important effector in neuroinflammation resolution.