“Leaky gut syndrome” is a phrase that you may have heard before, and for good reason: it is quickly becoming a focus of greater interest and study for physicians and patients alike. While it is a relatively new concept and some specifics are still being determined, there are a number of studies that have been able to dive into what exactly it is and what problems it may be correlated with. Doctors and scientists are increasingly focused on discovering how a leaky gut can affect the brain and actually prompt or further develop neurodegenerative diseases such as dementia and Alzheimer’s, Parkinson’s, and even mood and mental health disorders in people of all ages.
Well, first - what is leaky gut syndrome?
“Leaky gut syndrome” is another way to say “increased intestinal permeability”. Though the intestines are meant to be somewhat permeable, this syndrome is caused by the dysfunction of tight junctions, which are a specific type of barrier between intestinal cells. Tight junctions work together with layers of intestinal mucus to create a mucosal lining that acts as a physical barrier. This barrier keeps pathogens, bacteria, macromolecules, and other environmental toxins contained within the intestines (1, 2, 3, 4). If the barrier is compromised in some way, these toxins and pathogens can escape the intestine (2). A variety of factors can reduce the effectiveness of tight junctions, compromise the barrier, and lead to leaky gut, including an imbalanced gut microbiome and chronic inflammation (2).
How are the gut microbiome and inflammation correlated?
Each person’s gut contains a specific and unique set of microbes that work together to aid our digestive and immune systems, among other functions. A balanced gut will help keep your brain, digestive, and nervous systems healthy, while an imbalanced gut is a risk factor for countless problems (4).
Healthy gut microbiota support the mucosal barrier and regulate the foreign pathogens that enter the body through antimicrobial and immunological properties (2). They also play a role in the body’s ability to regulate brain chemicals, including neurotrophins like brain-derived neurotrophic factor, which support neuron regeneration and overall survival (4). When the gut is dysregulated due to a number of factors (discussed in more detail below), not only does the body become less effective at regulating the systems and chemicals mentioned above, it also leads to a weakened mucosal barrier (1, 2). Pathogens are able to escape more easily, and then the body’s immune system responds with an inflammatory response (1, 2). This response can promote further dysregulation of gut microbiota, more inflammation, and continued leaking in an already weakened intestinal mucosal barrier, creating a cycle of hyperpermeability (1).
Where do the escaped macromolecules go?
Once a harmful pathogen, bacteria, or macromolecule escapes the intestines through leaky tight junctions, they can end up anywhere in the body if they enter the bloodstream (2, 5). This may cause widespread peripheral inflammation, including in the brain. This gut-related brain inflammation can also lead to the breakdown of the blood-brain barrier, resulting in “leaky brain” (3, 5). Leaky brain, unfortunately, means that these pathogens are able to reach and affect the brain, promoting a wide array of brain issues and disorders (5).
While there is some debate about the extent of brain inflammation and the breakdown of the blood-brain barrier causing these brain disorders in the general population, there is a clear association between those with existing genetic predispositions and compromised barriers (2). Rogue toxins, bacteria, and other pathogens may actually trigger and help progress the development of certain diseases and cognitive decline in those with predispositions, including general neurodegeneration, Alzheimer’s and Parkinson’s diseases, and other memory and mood disorders (2, 5)
Cognitive Decline and Memory Disorders
Cognitive decline and memory disorders, like dementia and Alzheimer’s disease, are known to be caused by the degeneration of brain tissue, and reduced function and plasticity (6). Toxins that are leaked from the gut and blood-brain barrier and attach to vulnerable neurons, chronic inflammation due to leaky gut, and the immune system’s response to that chronic inflammation can all contribute to this degeneration (7, 10). Beyond that, the dysregulation of the gut microbiome that preludes leaky gut can also lead to disruption of the gut’s secretion of different types of brain chemicals and proteins, such as brain-derived neurotrophic factor (BDNF) (4). Disruption or decrease in the levels of BDNF can reduce brain plasticity, development, and even affect the brain’s physical structure (4, 8). This can lead to issues with memory and learning and is associated with neurodegeneration and the development of dementia and Alzheimer’s (8).
Other neurodegenerative diseases, such as Parkinson’s, have very similar origins and effects as compared to the cognitive decline and the memory disorders listed above. Studies on Parkinson’s Disease have shown that it is very likely to begin because microbes have entered the blood-brain barrier, due to inflammation and increased intestinal permeability (3, 7). Interestingly enough, those with Parkinson’s disease often have ongoing intestinal dysfunction in the form of constipation, and constipation can actually begin to manifest in those suffering from Parkinson’s disease years before other symptoms manifest (7).
Low Mood and Mood Disorders
The gut microbiome plays a huge role in our mood and mental stability as well, and even the development of some mental health disorders (3). Because changes in microbiota correlate to changes in brain chemistry, a gut microbiome disruption due to illness, antibiotics, etc., can be associated with abnormal behavior and cognition, including mood disruption, depression, and anxiety (3). If this change in the microbiome causes leaky gut and thus weakens the mucosal lining and increases permeability, inflammation can be another driver of mood disruption (9). And unfortunately, just as hyperpermeability can be cyclical, inflammation can also be both a cause and result of depression (9).
So, how do you break these cycles?
Because the matter of whether or not a leaky gut is a cause or result of these disorders is still being studied, it can also be helpful to improve brain health as well. You can find more information on overall brain health and the five pillars of health, hormones’ effects on brain health, and the correlation between blood sugar on brain health in these articles.
Another answer to healing leaky gut is very straightforward: protect and heal the gut microbiome! If gut microbiota are well-balanced and healthy overall, it results in stronger tight junctions and better mucosal lining, thus reducing intestinal hyperpermeability.
In order to improve gut microbiome health, it can be helpful to focus on:
Improving your diet to include more fruits, vegetables, healthy fats, and lean meats
Avoiding excessive sugar and/or alcohol consumption
Taking prebiotics and probiotics daily
Avoiding and/or quickly addressing any type of severe infection, burn, and illness
While approaching gut health or changing some of the habits listed above may seem overwhelming, the good news is that you are not alone! We at TCIM love to partner alongside anyone who is seeking greater health. Whether you are experiencing gut and inflammation issues yourself, are looking for better brain health for your developing child, or are looking to improve your care for a parent with dementia, we can help! Please reach out to schedule a consultation - we would love to partner with you to determine the best solutions and treatments to get you and your loved ones on the path toward greater health.
Jonathan Vellinga, MD is an Internal Medicine practitioner with a broad interest in medicine. He graduated Summa cum laude from Weber State University in Clinical Laboratory Sciences and completed his medical degree from the Medical College of Wisconsin.
Upon graduation from medical school, he completed his Internal Medicine residency at the University of Michigan. Dr. Vellinga is board-certified with the American Board of Internal Medicine and a member of the Institute for Functional Medicine.
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Mu, Q., Kirby, J., Reilly, C. M., & Luo, X. M. (2017, May 23). Leaky Gut As a Danger Signal for Autoimmune Diseases. Frontiers in immunology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/.
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Houser, M. C., & Tansey, M. G. (2017). The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis?. NPJ Parkinson's disease, 3, 3. https://doi.org/10.1038/s41531-016-0002-0
Bathina, S., & Das, U. N. (2015). Brain-derived neurotrophic factor and its clinical implications. Archives of medical science : AMS, 11(6), 1164–1178. https://doi.org/10.5114/aoms.2015.56342
Bested, A. C., Logan, A. C., & Selhub, E. M. (2013). Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II - contemporary contextual research. Gut pathogens, 5(1), 3. https://doi.org/10.1186/1757-4749-5-3
Li, Z., Zhu, H., Zhang, L., & Qin, C. (2018, September 25). The intestinal microbiome and Alzheimer's disease: A review. Wiley Online Library. https://onlinelibrary.wiley.com/doi/full/10.1002/ame2.12033.