Lactobacillus acidophilus LA3 suppresses neuroinflammation via the gut-brain axis by enriching indole-3-acetic acid (IAA) production and acting through an AHR-dependent mechanism, representing a promising next-generation probiotic targeting neurological health.
Key Findings
Results
Lactobacillus acidophilus LA3 demonstrated superior efficacy in suppressing LPS-induced proinflammatory cytokines in BV-2 microglia compared to other tested strains.
BV-2 microglia were used as the in vitro neuroinflammation model, stimulated with lipopolysaccharide (LPS)
LA3 was identified as a potent probiotic strain among those screened for anti-neuroinflammatory activity
Suppression of proinflammatory cytokines was the primary in vitro outcome measure
LA3 was described as having 'superior efficacy' relative to comparator strains tested
Results
LA3 alleviated systemic and neuroinflammation, depressive-like behaviors, and cognitive impairment in an LPS-induced murine model.
An LPS-induced murine model was used to assess in vivo neuroinflammatory and behavioral outcomes
Outcomes measured included markers of systemic inflammation, neuroinflammation, depressive-like behaviors, and cognitive impairment
LA3 treatment reversed these LPS-induced changes in the animal model
Both behavioral and biochemical endpoints were assessed in vivo
Results
LA3 restored blood-brain barrier and gut-vascular barrier integrity in LPS-challenged mice.
LPS challenge disrupted both the blood-brain barrier (BBB) and the gut-vascular barrier (GVB)
LA3 administration reversed barrier disruption as part of its protective effects
Restoration of dual barrier integrity was identified as a mechanistic component of LA3's neuroprotective action
Barrier integrity is considered a key interface in gut-brain axis communication
Results
LA3 reversed gut microbiota dysbiosis and enriched short-chain fatty acid-producing bacteria in LPS-treated mice.
LPS-induced murine model exhibited gut microbiota dysbiosis that was reversed by LA3 treatment
LA3 specifically enriched populations of short-chain fatty acid (SCFA)-producing bacteria
Microbiota modulation was identified as part of the mechanism by which LA3 influences the gut-brain axis
SCFA-producing bacteria are associated with anti-inflammatory and gut-protective effects
Results
LA3 promoted elevated levels of indole-3-acetic acid (IAA) in both colonic contents and brain tissue.
IAA levels were measured in colonic contents and brain tissue of treated animals
LA3 treatment increased IAA concentrations in both compartments compared to controls
IAA elevation in the brain suggests gut-derived IAA crosses or influences the blood-brain barrier
IAA was identified as 'an important effector in neuroinflammation resolution'
Results
The anti-inflammatory effect of LA3 was confirmed to be AHR-dependent, as demonstrated by AHR inhibitor experiments in BV-2 cells.
An aryl hydrocarbon receptor (AHR) inhibitor was used to confirm mechanistic dependence
Inhibition of AHR abrogated or reduced LA3's anti-inflammatory effects in BV-2 microglia
IAA is a known AHR ligand, linking the metabolite to the identified signaling pathway
AHR-dependent signaling was identified as the molecular mechanism mediating LA3's neuroinflammatory suppression
Results
Both LA3 fermentation supernatant and exogenous IAA administered at the same dose detected in the supernatant recapitulated key aspects of LA3's anti-inflammatory effects.
LA3 fermentation supernatant was tested separately from intact bacteria and reproduced key effects
Exogenous IAA was administered at a dose matching the concentration detected in the LA3 fermentation supernatant
Both conditions recapitulated 'key aspects of LA3's effects,' implicating IAA as a primary active effector
This dose-matching experimental design provided evidence that IAA accounts for a significant portion of LA3's bioactivity
What This Means
This research suggests that a specific probiotic strain called Lactobacillus acidophilus LA3 can reduce brain inflammation (neuroinflammation) by working through the gut-brain axis — the communication network between the digestive system and the brain. In laboratory experiments using brain immune cells and in mouse models where inflammation was triggered by a bacterial toxin (LPS), LA3 outperformed other tested strains in reducing inflammatory signals. In mice, LA3 also improved depression-like behaviors, cognitive function, and restored the protective barriers that separate the gut and brain from harmful substances.
A key finding was that LA3 appears to work largely by boosting production of a natural compound called indole-3-acetic acid (IAA), which was elevated in both the gut and brain of LA3-treated mice. IAA activates a cellular receptor called AHR (aryl hydrocarbon receptor), and when researchers blocked this receptor, LA3's anti-inflammatory benefits were diminished — confirming IAA-AHR signaling as a central mechanism. Importantly, when researchers tested just the liquid byproducts of LA3 fermentation, or gave mice IAA directly at the same dose found in that liquid, they saw similar protective effects, strongly pointing to IAA as the key active ingredient.
This research suggests that LA3 could be developed as a targeted probiotic for conditions involving neuroinflammation, such as depression or cognitive decline, and that the metabolite IAA may itself be a promising therapeutic target. The study highlights the gut microbiome as a potential pathway for influencing brain health, with specific bacterial strains and their metabolic products playing meaningful roles in the gut-brain communication system.
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Chen Y, Li M, Wang J, Ji L, Xu Y, Wang X, et al.. (2026). Lactobacillus acidophilus LA3 Suppresses Neuroinflammation via the Gut-Brain Axis.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c04375