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Depression and the Microbiome: The Gut and Neuroregulation

A malfunctioning system.

by Malay Nanavaty

How Does the Microbiome Contribute to Depression?

Depression is a condition that has grown much more prevalent around the world in the last few decades. Approximately 350 million people are thought to be depressed around the globe. That’s more than the entire population of the United States! With such a large patient base, this disease demands our attention as a species. In recent years, the field of depression research has become quite popular. Associations between depression and other factors are being discovered rapidly. As you may have guessed, the microbiome has emerged as one of these associative factors. In this post, I will break down the fundamentals of this emerging research.

Association Studies

A lot of evidence supporting this theory is associative. Several studies have found that germ free laboratory mice begin to show depressive symptoms rapidly after being transplanted with a microbiome sample from depressed mice. Additionally, depressed mice tend to have a less diverse and less abundant microbiome than their healthy counterparts.

In humans, such a trend is observed between IBS presence and depression. Research has confirmed that IBS patients have a poorly diversified microbiome. More interestingly, further research has shown that people that suffer from worse IBS tend to have frequent bouts of depression across their lives. This suggests that more disorganized microbiomes tend to produce higher levels of depressions in their hosts.

The Role of Inflammation in Depression

The microbiome and depression are directly connected to each other by their reliance on immuno-inflammatory molecules for functioning. A healthy microbiome seeks to keep inflammation down in order to maintain a healthy living environment in the gut without the immune system attacking its symbionts. This lowering of the baseline inflammation is helpful to the brain as well, since it signals that there is no need to be stressed right now. This process begins to fail when the microbiome is compromised.

A Failed System

In the case where a suboptimal microbiome has taken root, things look quite different. The poorly established microbe community is less able to keep the immune system regulated. As a result, the immune system interprets the microbes’ presence as dangerous and releases inflammatory molecules known as lipopolysaccharides (LPS). These molecules are received by the brain’s immune cells (microglial cells). Sensing an impending threat, these molecules release cytokines, which stimulate the anxiety system in the brain.

This signalling pathway keeps the host chronically prone to stress and anxiety. Over time, this hyperreactivity exhausts the host and manifests as depression. Unfortunately, this is a positive feedback loop; depression induces more cytokine release, which causes a worse depression. This can easily become crippling when combined with the negative effects of poor diet and exercise habits on the microbiome.

Other Microbiome-Destabilizing Contributors

As most of you know, the largest controllable variable that you can regulate your microbiome with is your diet. Changing your diet can allow you to both alter your existing microbiome (to an extent) as well as directly change your gut’s inflammatory signalling pathway. Thus, it is important to make sure that you take care of your eating habits for both physical and mental reasons.

Having chronic social stressors have also been shown to affect one’s microbiome. In this instance, the chronic stress triggers inflammation directly, which damages your microbiome’s relationship with your immune system in turn. This can initiate the downward spiral seen in the depression cycle we mentioned above.


Depression is a serious issue with multiple facets of complexity. Through laboratory observation, it appears that the microbiome plays a large part in the regulation of this disease. The microbiome has already been shown to have tight links to the brain in early development, making its role in mental illness unsurprising. As more research is done in the coming years, specific therapies may emerge to remedy these problems. However, until then, the most practical thing we can do is maintain a healthy microbiome by making informed decisions regarding our lifestyle.

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Energy extraction gone wild.

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