Lactobacillus acidophilus LA3 Suppresses Neuroinflammation via the Gut-Brain Axis

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.