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The activation impact of lactobacillus-derived extracellular vesicles on lipopolysaccharide-induced microglial cell
Yanfang Yang1, Na Li1, Yubo Gao1
1Department of Anaesthesia and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
Abstract:
Perioperative neurocognitive dysfunction (PND) emerges as a common postoperative complication among elderly patients. Currently, the mechanism of PND remains unclear, but there exists a tendency to believe that inflammation plays a significant role in PND. Alterations in the abundance of intestinal microbiota can increase the permeability of the intestinal mucosal barrier and incite extraintestinal inflammatory responses. Metabolites from these microbiota can be absorbed by the intestinal mucosa into the bloodstream, exerting influence upon the central nervous system (CNS). Lactobacillus (Lac), serving as an intestinal probiotic bacterium, possesses the capacity to modulate emotional behavior and cognitive functions. Extracellular vesicles (EVs) are recognized as novel therapeutic carriers for targeted delivery to regulate physiology and pathogenesis. While the mechanism governing the primary function of Lac-EVs in the CNS remains uncertain. Therefore, we established an in vitro neuroinflammation model to induce PND and then treated the mice with Lac-EVs to observe the effect of these EVs on neuroinflammation, particularly on microglial (MG) polarization. Our research unveils that Lac-EVs reduced inflammation induced by LPS in microglia and the activation of related proteins, including the mRNA expression of M1 labeled protein (iNOS). Moreover, the mRNA expression of M2-labeled protein (Arg1) increased. In addition, flow cytometry revealed that the ratio of M1/M2 microglia also changed significantly. Therefore, Lac-EVs promoted the differentiation of M2 microglia by inducing the preferential expression of specific markers related to M2 macrophages and inflammation. In terms of inflammatory cytokine expression, Lac-EVs decreased the secretion of proinflammatory cytokines (IL-1β and IL-6) and increased IL-10 production after lipopolysaccharide (LPS) stimulation. Therefore, Lac-EVs induce the activation of M2 microglial cells without inducing cellular harm in vitro, and they demonstrate anti-inflammatory effects against lipopolysaccharide-induced neuroinflammation. This finding suggested that it is an effective anti-inflammatory strategy for alleviating inflammation-driven PNDs.
Insights
Lactobacillus extracellular vesicles (Lac-EVs) reduce neuroinflammation and promote beneficial M2 microglial polarization, offering a potential strategy for preventing inflammation-related perioperative neurocognitive dysfunction (PND) in elderly patients.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Perioperative neurocognitive dysfunction (PND) is a common postoperative complication in elderly patients.
- Neuroinflammation, potentially linked to gut microbiota alterations, is implicated in PND pathogenesis.
- Lactobacillus (Lac) probiotics and their extracellular vesicles (EVs) show potential for modulating CNS functions.
Purpose of the Study:
- To investigate the therapeutic potential of Lac-EVs in an in vitro neuroinflammation model of PND.
- To determine the effect of Lac-EVs on microglial (MG) polarization and inflammatory responses.
Main Methods:
- Established an in vitro neuroinflammation model using lipopolysaccharide (LPS) to mimic PND.
- Treated the model with Lactobacillus extracellular vesicles (Lac-EVs).
- Assessed microglial polarization (M1/M2 markers, iNOS, Arg1), inflammatory cytokine secretion (IL-1β, IL-6, IL-10), and cellular viability.
Main Results:
- Lac-EVs reduced LPS-induced inflammation in microglia, decreasing M1 marker (iNOS) and increasing M2 marker (Arg1) mRNA expression.
- Lac-EVs shifted microglial polarization towards the M2 phenotype, as confirmed by flow cytometry.
- Lac-EVs suppressed pro-inflammatory cytokines (IL-1β, IL-6) and enhanced anti-inflammatory cytokine (IL-10) production.
Conclusions:
- Lac-EVs promote M2 microglial activation and exhibit anti-inflammatory effects in vitro without causing cellular harm.
- Lac-EVs represent a promising therapeutic strategy for mitigating inflammation-driven perioperative neurocognitive dysfunction.
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