The Blood Brain Barrier and Neuroinflammation

Dr. David Wiss

July 4, 2021

Mental Health

With the “nutrition for mental health” revolution in full swing, many unanswered questions remain. However, robust data on the “gut-brain axis” has begun to elucidate the various mechanisms linking food consumption to mood, behavior, and cognition. Recent review articles point to prebiotics (which include dietary fiber, polyphenols, and resistant starch) as the missing links in the Standard American Diet (SAD), driving the depletion of gut microbial species [1,2] and increased intestinal permeability [3], which is sometimes described as “leaky gut.”

Hundreds of studies have identified links between the gut microbiota brain axis and the mind, explaining how metabolites produced by gut bacteria have implications for mental and behavioral health [4,5]. Such metabolites include neurotransmitters, short-chain fatty acids (SCFA), and other “postbiotics” (i.e., compounds created by probiotic bacteria). Additional signaling molecules made or influenced by gut bacteria will likely emerge as communicators across multiple body systems. One important gatekeeper in this system is the blood-brain barrier, a critical component linking gut health to mental health.

Many individuals experience brain fog or other symptoms of a “leaky brain.” In some cases, this can be related to food allergies or food sensitivities. While many alternative practitioners have made connections between leaky gut syndrome and brain inflammation for decades, only recently has it become accepted in the Western medicine model. There is a revolution going on in our understanding of brain health and how nutrition can be a part of the solution. The key is to repair the intestinal walls through an anti-inflammatory diet.  While there are many approaches to improving chronic inflammation, nutrition is often ignored in most medical practices.  

The blood-brain barrier separates the central nervous system from peripheral circulation [6]. It is composed of neurovascular endothelial cells with tight junctions between them. Glial cells (astrocytes and microglia) and neurons contribute to the blood-brain barrier integrity. They are considered the principal immune mediators in the brain. Ideally, the blood-brain barrier will be intact and not “leaky,” as observed in the gut, for example, in those with chronic alcohol dependence [7]. Permeability in the brain has been associated with early-life adversity [8] and has been under active surveillance for neurodegenerative diseases (e.g., Alzheimer’s, multiple sclerosis, Parkinson’s disease) [9]. This is a hot topic relevant to many adverse mental health conditions. It is likely to be relevant for all people!

Several recent reviews have proposed that gut-based immune responses leading to inflammation are likely to play a role in altered reward processing and reactivity, suggesting a potential role of neuroinflammation in both depression and addictions [10–12]. Who knew that inflammation could travel to the brain? It turns out neurotoxic molecules such as pro-inflammatory cytokines can lead to “leaky brain” [13]. 

It has been proposed that neuroinflammation in the amygdala (part of the limbic system) contributes directly to anxiety and autonomic distress in alcohol/drug withdrawal [14]. More research is needed to pinpoint specific regions of the brain that become inflamed across different psychiatric diagnoses. For example, considerable effort has gone into understanding the biological signature of post-traumatic stress disorder [15]. It has recently been concluded that it may be a systemic illness with somatic pathology [16].

The extent to which nutrition interventions can reverse neuroinflammation in humans remains unknown. In the meantime, why not capitalize on the information that we do have? We know that reducing inflammation in the gut with soluble fiber can improve neuroinflammation [17]. We also know that nutrition interventions, including probiotics and prebiotics that positively impact postbiotic production, have a wide range of benefits. However, this effect is more pronounced for some than for others. Does it seem relevant to you?

Wise Mind Nutrition has created personalized nutrition interventions that are designed to identify those who would benefit most from focusing on gut health, without needing to undergo drastic elimination diets. High-fiber diets with lots of colorful fruits and vegetables rich in polyphenols are the most established anti-inflammatory dietary approaches. The goal is to increase bacterial diversity. We have developed cutting-edge methods that use nutrition to reduce inflammation and thereby improve mood. Keep in mind: nutrition might not change us overnight, but it changes us over time. Start the revolution today—your future self will be eternally grateful!

References

1. Swann OG, Kilpatrick M, Breslin M, Oddy WH. Dietary fiber and its associations with depression and inflammation. Nutr Rev. 2019;

2. Deehan EC, Walter J. The Fiber Gap and the Disappearing Gut Microbiome: Implications for Human Nutrition. Trends in Endocrinology & Metabolism. 2016;27(5):239–42.

3. Leech B, McIntyre E, Steel A, Sibbritt D. Risk factors associated with intestinal permeability in an adult population: A systematic review. International Journal of Clinical Practice. 2019;e13385.

4. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701–12.

5. Person H, Keefer L. Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis. Prog Neuro-psychopharmacology Biological Psychiatry. 2020;110209.

6. Huang X, Hussain B, Chang J. Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms. Cns Neurosci Ther. 2021;27(1):36–47.

7. Leclercq S, Cani PD, Neyrinck AM, Stärkel P, Jamar F, Mikolajczak M, et al. Role of intestinal permeability and inflammation in the biological and behavioral control of alcohol-dependent subjects. Brain, Behavior, and Immunity. 2012;26(6):911–8.

8. Finnell JE, Wood SK. Putative Inflammatory Sensitive Mechanisms Underlying Risk or Resilience to Social Stress. Frontiers in Behavioral Neuroscience. 2018;12:240.

9. Chen W-W, Zhang X, Huang W-J. Role of neuroinflammation in neurodegenerative diseases (Review). Mol Med Rep. 2016;13(4):3391–6.

10. Dooley LN, Kuhlman KR, Robles TF, Eisenberger NI, Craske MG, Bower JE. The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. Neurosci Biobehav Rev. 2018;94:219–37. 11. Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20(2):145–55.

12. Kohno M, Link J, Dennis LE, McCready H, Huckans M, Hoffman WF, et al. Neuroinflammation in addiction: A review of neuroimaging studies and potential immunotherapies. Pharmacol Biochem Behav. 2019;179:34–42.

13. Morris G, Fernandes BS, Puri BK, Walker AJ, Carvalho AF, Berk M. Leaky brain in neurological and psychiatric disorders: Drivers and consequences. Australian New Zealand J Psychiatry. 2018;52(10):924–48.

14. Gorky J, Schwaber J. The role of the gut-brain axis in alcohol use disorders. Prog Neuro-psychoph. 2015;65:234–41. 15. Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW, et al. Biological studies of post-traumatic stress disorder. Nat Rev Neurosci. 2012;13(11):769–87.

16. Mellon SH, Gautam A, Hammamieh R, Jett M, Wolkowitz OM. Metabolism, Metabolomics, and Inflammation in Post-Traumatic Stress Disorder. Biological Psychiatry. 2018;83(10):866–75.

17. Matt SM, Allen JM, Lawson MA, Mailing LJ, Woods JA, Johnson RW. Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice. Front Immunol. 2018;9:1832.