The Microbiome-Brain Axis: How Your Gut Bacteria Affect Your Mood, Memory, and More

When we think of the gut, we tend to focus on its role in digestion. However, recent research has revealed that the gut is much more than just a system for breaking down food. In fact, the gut is home to trillions of bacteria that play a crucial role in our overall health and well-being. The microbiome has been linked to everything from immune function to weight management. But perhaps the most surprising connection is the one between the microbiome and the brain. Scientists now understand that the gut and the brain are intimately connected, and that the bacteria in our gut can affect our mood, memory, and even our behaviour. This connection, known as the microbiome-brain axis, is a fascinating area of research that has significant implications for our understanding of mental health and disease. In this article, we'll explore the latest research on the microbiome-brain axis and what it means for our health and well-being.

What is the Microbiome?

The human microbiome is a complex ecosystem of bacteria, viruses, fungi, and other microorganisms that live in and on our bodies. The majority of these microorganisms reside in our gut, where they play a crucial role in maintaining our overall health. The microbiome is a dynamic system that is influenced by a variety of factors, including genetics, diet, and lifestyle.

The bacteria in the microbiome can be either gram-negative or gram-positive. Gram-negative bacteria have an outer shell made of lipopolysaccharides or LPS. When the bacteria die, the LPS is released, and it is inflammatory. In a healthy gut, this LPS is usually contained in the mucosal barrier of the gut lining and is eventually excreted with other fecal matter. Some may pass through the tight junctions of the gut lining and make its way to the circulatory system. This is where the immune system kicks into gear and starts a short-lived inflammatory response to contain it. And all is good.
Recent research has revealed that the microbiome is involved in many important physiological processes, including digestion, immune function, and metabolism. The microbiome also plays a crucial role in the development and maintenance of the gut-brain axis, a bidirectional communication pathway that connects the gut and the brain.

The Gut-Brain Connection

The gut-brain connection is not a new concept, but recent research has shed new light on its importance. There are two important pathways:

1. Via the Vagus Nerve   

The gut and the brain are connected via the vagus nerve, which is the longest nerve in the body. This nerve runs from the brainstem to the abdomen and is responsible for transmitting signals between the gut and the brain. In addition, the gut is also home to a complex network of neurons, known as the enteric nervous system, which operates independently of the central nervous system.
The gut-brain connection is a two-way street. Not only can the brain influence the gut, but the gut can also influence the brain. For example, when we're stressed, the brain sends signals to the gut that can lead to digestive issues. On the other hand, the bacteria in our gut can produce neurotransmitters, such as serotonin and dopamine, which play a crucial role in regulating mood and behaviour.

Effect on Mood
Neurotransmitters, such as serotonin, play a role in regulating mood. Serotonin is often referred to as the "feel-good" hormone, as it's associated with feelings of happiness and well-being. In fact, it's estimated that up to 90% of the body's serotonin is produced in the gut. 
Research suggests that people with certain types of gut bacteria have lower levels of depression and anxiety. For example, one study found that people who consumed a probiotic containing Lactobacillus and Bifidobacterium had lower levels of anxiety and depression than those who did not consume the probiotic. Both are gram-positive bacteria and may produce serotonin.

Effect on Cognition
Research in humans has also shown a link between the microbiome and cognitive function. One study found that people who consumed a probiotic containing Lactobacillus and Bifidobacterium had improvements in cognitive function compared to those who did not consume the probiotic. Another study found that people who had a high diversity of gut bacteria had better cognitive function than those with a low diversity of gut bacteria.

2. Via ‘Leaky’ Gut Lining   

When you have an autoimmune disorder you will have increased permeability in the gut lining – leaky gut. The gut lining has lost its integrity and its ability to act as a barrier to toxins such as LPS. In addition, you will most likely have gut dysbiosis or an imbalance in the gut bacteria. This can mean more gram-negative bacteria. Gram-negative bacteria also tend to be more pathogenic. There are two mucosal layers - the one closest to the center of the gut is more fluid and acts to move gut content along. The inner layer is more gel-like and acts as a barrier for the gut lining.  

Effect on Inflammation
All bacteria love to feed on the mucosal layers. Gram-positive bacteria will eat and stimulate replacement of the mucin in the layers. Gram-negative bacteria eat but don’t replace. So if you have a lot more gram-negative bacteria than gram-positive, the mucosal layers will eventually be eaten away, exposing the gut lining. The integrity of the gut lining will then fail allowing LPS to flood into the blood stream and circulate throughout the body. Your immune system will initiate an inflammatory response to try to contain it. But if LPS continues to flood the system, your immune system will be continuously responding.

Current research suggests that if you have LPS in the gut, you will have it in the brain tissues. What are the consequences?

• A study has shown that LPS-stimulated inflammation is associated with sickness behaviour symptoms such as anorexia, low concentration, low energy, loss of libido, irritability, and malaise.
• Another study found that LPS-stimulated inflammation was associated with severe depression and anxiety even after adjusting for lifestyle and health factors.
• Other studies found strong relationships between LPS-stimulated inflammation and Alzheimer's, Parkinson’s, and the mechanisms behind type 2 diabetes.

Factors that Affect the Microbiome-Brain Axis

There are several factors that can affect the microbiome-brain axis. One of the biggest factors is diet. A diet that is high in processed foods and low in fiber can lead to an imbalanced microbiome, which can have a negative impact on mental health. On the other hand, a diet that is high in fiber and plant-based foods (including fruits, vegetables, whole grains, legumes, and fermented foods) can promote a healthy microbiome and improve mental health.

Other factors that can affect the microbiome-brain axis include stress, antibiotics, and sleep. Chronic stress can lead to an imbalanced microbiome, while antibiotics can disrupt the microbiome causing an imbalance between gram-negative and gram-positive bacteria. Lack of sleep can also have a negative impact on the microbiome and mental health.

Probiotics and Their Impact on the Microbiome-Brain Axis

Probiotics are popular supplements that aim to restore balance to the microbiome by increasing the number of beneficial bacteria. Unfortunately, most probiotics on the market are not particularly useful. Almost all probiotic bacteria will not survive travel through the digestive tract due to stomach acid. Those that do survive, do not colonize in the gut. So, any positive effect is short-lived. A very small number of probiotics are spore-based and can survive and colonize the gut. But care must also be taken in the decision to use a spore-based probiotic. Because of its ability to establish itself and grow, you must be confident that the species of bacteria is a good fit for your microbiome. If not, it may make an imbalance problem even worse. You should get advice from a medical practitioner before embarking on this course.

Lifestyle changes to improve gut health and mental well-being

In addition to diet, there are several lifestyle changes that can help improve gut health and mental well-being. These include reducing stress, getting enough sleep, and exercising regularly. Stress reduction techniques, such as meditation and yoga, can be particularly effective in improving gut health and mental well-being.

Implications for Hashimoto’s and Other Autoimmune Disorders

There are three general root causes of an autoimmune disorder: genetic predisposition, ‘leaky’ gut lining, and exposure to toxins. It is the last two that have direct effects on the microbiome. Exposure to toxins such as antibiotics and other drugs can lead to the imbalance in gut bacteria that can cause damage to the gut lining. As mentioned above, this damage leads to inflammation with which the immune system can struggle. In Hashimoto’s, this inflammation attacks the thyroid and, as recent research suggests, LPS-induced inflammation can have effects reaching well beyond the thyroid to the brain and other tissues. Hence, the very diverse symptoms experienced by Hashimoto’s sufferers and also those with other autoimmune disorders.

Conclusion

The gut and the brain are intimately connected, and the bacteria in our gut can affect our mood, memory, as well other body functions. Maintaining a healthy microbiome through diet, and lifestyle changes can have a positive impact on mental and physical well-being.

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Resources

van Eeden, W.A., van Hemert, A.M., Carlier, I.V.E. et al. Basal and LPS-stimulated inflammatory markers and the course of individual symptoms of depression. Transl Psychiatry 10, 235 (2020). https://doi.org/10.1038/s41398-020-00920-4

Vogelzangs N, de Jonge P, Smit JH, Bahn S, Penninx BW. Cytokine production capacity in depression and anxiety. Transl Psychiatry. 2016 May 31;6(5)  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070051/

Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24. PMID: 18283240. https://pubmed.ncbi.nlm.nih.gov/18283240/