The Synthesis of Wellness®

142. Neuroinflammation & Gut-Derived Lipopolysaccharides | Addressing Intestinal Dysbiosis, Intestinal Hyperpermeability, & Cognitive Function | Supporting the Gut-Microbiota-Brain Axis


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In today's episode, we dive into the molecular mechanisms underlying neuroinflammation, with a particular focus on how gut-derived endotoxins, such as lipopolysaccharides (LPS), perturb the blood-brain barrier (BBB) and propagate neuroinflammatory cascades. In more detail, we’ll discuss how intestinal dysbiosis and increased intestinal permeability can allow endotoxins such as LPS to enter systemic circulation and cross the blood-brain barrier (BBB), where they activate microglia via the TLR4 signaling pathway. We will explore symptoms including brain fog, memory impairment, mood disturbances, decreased concentration, and cognitive fatigue; as well as tools to support the gut-microbiota-brain axis.


Topics:

1. Introduction to Neuroinflammation

- Definition and general overview

- Key brain cells: neurons, glial cells, and endothelial cells

- Chronic neuroinflammation and microglial cells


2. Cellular Mechanisms of Neuroinflammation

- Role of microglia in detecting damage or infection

- Microglial activation through PRRs/TLRs

- Release of pro-inflammatory cytokines and reactive oxygen species (ROS)

- Impact on neurons and synaptic plasticity: memory and learning


3. Astrocytes in Neuroinflammation

- Astrocytes' contribution to the inflammatory response


4. Chronic Neuroinflammation and Brain Health

- Prolonged activation: oxidative stress, excitotoxicity, impaired synaptic function

- Impairment of synaptic plasticity and cognitive decline

- Mitochondrial dysfunction and cell death cascades

- Compromised blood-brain barrier integrity


5. Contributing Factors to Neuroinflammation

- Environmental toxins and pollutants, viral or bacterial infections, chronic sleep deprivation, and more


6. Intestinal Dysbiosis and Neuroinflammation

- Role of Gram-negative bacteria and LPS (lipopolysaccharides)

- Increased intestinal permeability and passage of LPS

- LPS transport: transcellular and paracellular pathways

- Impact on the blood-brain barrier (BBB)


7. LPS Activation of Microglia

- LPS binding to TLR4 on immune cells

- Microglial activation and cytokine release

- Cognitive impairments and neurodegenerative processes


8. Intestinal Hyperpermeability

- Bioindividual approaches: prebiotics, probiotics, polyphenols, bacteriophages

- Support for intestinal mucus secretions and sources of mucilage

- Butyrate

- Glutamine


9. Beneficial Gut Microbiome-Derived Metabolites and Brain Health

- Types of metabolites: SCFAs, tryptophan metabolites, polyphenol metabolites

- Role of butyrate in crossing the BBB and modulating brain function

- Influence on gene expression and synaptic plasticity

- Contribution to gut barrier integrity and protection against endotoxins


10. Conclusion

- Recap of neuroinflammation's impact on cognitive function + symptoms


Thank you to our episode sponsor:

1. Check out ⁠⁠⁠⁠⁠Daily Nouri⁠⁠⁠⁠⁠ and use code ⁠⁠⁠⁠⁠CHLOE20⁠⁠⁠⁠⁠ for 20% off your order.



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The Synthesis of Wellness®By Chloe Porter

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