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Lactobacilli Cell-Free Supernatants Modulate Inflammation and Oxidative Stress in Human Microglia via NRF2-SOD1
Mariagiovanna Di Chiano1, Maria Teresa Rocchetti2, Giuseppe Spano3
1Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Bari, Italy.
Cellular and Molecular Neurobiology
|September 17, 2024
Summary
Postbiotics from gut bacteria, specifically Lactobacilli-derived cell-free supernatants (CFSs), enhance microglial antioxidant responses. These CFSs activate the NRF2 pathway, boosting protective genes and reducing inflammation, offering potential neuroprotection against oxidative stress.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Microglia, the brain's immune cells, are crucial for neuronal protection.
- The gut-brain axis links gut microbes to brain function, influencing microglial activity.
- Nuclear factor erythroid 2-related factor 2 (NRF2) regulates oxidative stress response in microglia.
Purpose of the Study:
- To investigate the effects of Lactobacilli-derived cell-free supernatants (CFSs) on microglial responses to oxidative stress and inflammation.
- To explore CFSs' modulation of the NRF2 pathway and antioxidant gene expression in microglia.
- To assess CFSs' impact on pro- and anti-inflammatory cytokine levels in microglia.
Main Methods:
- HMC3 microglia were treated with CFSs from three human gut probiotic species.
- Microglia were exposed to lipopolysaccharide (LPS) to induce inflammation.
- NRF2 activation, antioxidant gene expression (HO-1, SOD, GST, GPx, CAT), SOD1 activity, and cytokine levels (TNF-α, IL-10) were measured.
Main Results:
- CFSs significantly increased NRF2 nuclear activity in both basal and inflamed conditions.
- Transcription of key antioxidant genes (HO-1, SOD, GST, GPx, CAT) was upregulated by CFSs, particularly after LPS stimulation.
- CFS pre-treatment attenuated pro-inflammatory TNF-α and increased anti-inflammatory IL-10 levels, with higher SOD1 activity observed.
Conclusions:
- Metabolites from gut microorganisms (Lactobacilli CFSs) can bolster microglial defense mechanisms against neuroinflammation and oxidative stress.
- CFS-mediated activation of the NRF2 pathway enhances the expression of cytoprotective genes in microglia.
- These findings suggest a potential therapeutic role for postbiotics in mitigating neurodegenerative diseases linked to oxidative stress and inflammation.

