Looking For a New Treatment for Depression? The Gut Microbiome Might be the Answer

By: Jonique George

Introduction

There’s a popular saying: “you are what you eat”. In many ways, this saying rings true. It’s been well established that a healthy diet can aid in the circumvention of various diseases. But wouldn’t it be nice if our diets could have a positive impact on mental health as well? Sure, eating a chocolate chip cookie when you’re sad usually makes the day seem a little brighter, but scientists are now investigating whether certain foods can actually give you some protection against various mood disorders like depression. To understand this, first we must understand what depression is.

Depression

Major depressive disorder, also known as depression, is a psychiatric/mood disorder that results in decayed mood, and may be accompanied by other symptoms like apathy, isolation tendencies, enjoyment difficulties, negative thoughts, and dejection [6]. Unfortunately, not only does this mood disorder drastically decrease general well-being, but it often leads to suicide. Patients with depression are nine times more likely to die by suicide compared to the general population [8], and in 2021, 21million Americans suffered from depression [7]. The root cause of depression has not yet been fully elucidated but many studies have shown that it is correlated with signaling disruptions in the amygdala region of the brain.

The Amygdala: Mediator of Emotions

Emotions are complex states, feelings, and responses that are regulated by the central nervous system. The most important region of the brain for regulation of emotional response is the amygdala, which is well connected with other brain structures; amygdala connectivity is

important because it allows for emotional computation based on sensory input from other brain regions [2, 26]. For example, the imagery of a rattlesnake near your foot needs to travel from the eye to various brain regions, eventually reaching the amygdala for processing, which allows for the appropriate response, fear, signaling danger. Damage to the amygdala interrupts emotional processing, including diminished fear response [28] and motivation [27], the latter of which is a crucial aspect of depression. People with depression have increased amygdalar blood flow and activation [4,5], and diminished connections from the amygdala to other brain regions [3]. Interestingly, this brain region not only connects to other areas of the brain, but also to the gut [1].

The Gut Microbiome

The gastrointestinal (GI) tract or digestive system is necessary for the breakdown of food and the absorption of nutrients in most animals. The major organs of the GI tract are the esophagus, stomach, and intestines. There’s something else that lurks in this system too. Deep in the large intestine live many different species of bacteria, viruses, and fungi that work in harmony with the host animal. We like to call these 100 trillion or so organisms the gut microbiome [29]. These bacteria are important for digestion because they secrete essential nutrients like Vitamin B, riboflavin, thiamine, nicotinic acid, and biotin, which are crucial for various bodily functions [24, 25], including brain functions.

The Relationship Between the Brain and Gut

The gut microbiome interacts heavily with the brain, and their bidirectional communication

system is often called the gut-brain axis. The mechanisms of this interaction are truly fascinating. The brain functions by using biochemical signaling molecules called neurotransmitters e.g., glutamate, dopamine, etc. to activate neurons and evoke effects. As it turns out, microbes in the gut can also produce neurotransmitters. Staphylococcus bacteria in the gut can produce dopamine and serotonin [9], which are two important neurotransmitters for amygdala signaling and modulation of depression. Also, the gut microbiome produces a compound called phenylethylamine, which can cross the barrier of the brain [10, 11]. The gut microbiome can also activate afferent nerves, which project to the brain. Increases in Lactobacillus rhamnosus in mice activates the vagus nerve, thereby altering mRNA levels of GABA, a neurotransmitter implicated in depression, in the amygdala [12]. Furthermore, the stimulation of the vagus nerve at points enervated with the upper GI tract increases feelings of reward in mice [13]. Therefore, the gut microbiome can influence the brain and mood, in many ways. So, how can we use food to modulate this system?

Food Intake and Mood

For years, it’s been known that diet can cause various cardiovascular diseases like Type II

diabetes [15, 16], hypertension [14], and obesity. Recent studies have shown that diet can

contribute to inflammatory diseases [18], neurodegenerative diseases [17], and even mood

disorders [19]. This is mostly accomplished by the effect of food on the gut microbiome.

Prebiotics are beneficial food substrates, usually types of fiber, that increase the growth or

activity of gut microbes [21]. Furthermore, native rice starch and inulin have been shown to have protective effects on Lactobacillus rhamnosus [22, 23]. Food’s role in increasing anti-depressive gut microbiome species have extremely interesting possible implications for dietary modulation on depression.

Conclusion

Scientists are currently investigating new therapeutic interventions for depression, and a new

potential contender is nutrition-based dietary modulation. Depression, which may be caused by abnormal signaling in the amygdala, can be attenuated by the gut microbiome. Gut bacteria like Staphylococcus and Lactobacillus rhamnosus secrete various neurotransmitters that can travel to the amygdala, where they can have anti-depressive effects. The strengths of the effects correlate with the number of microbes, and number of gut microbes can be increased by consumption of certain foods. Dietary fiber and prebiotics are examples of foods that aid the health and growth of these bacteria. Needless to say, food can have a larger impact on our mental health than we thought, and these studies are the first steps in creating nutrition-based therapeutics for treatment of mood disorders like depression.

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