The customary therapy for depression since the 1950s has been based on the theory that depression is caused by neurotransmitter imbalances in the brain. Therefore drugs that can positively affect this balance are the treatment of choice. But antidepressants have not proven to be an effective solution for many people suffering from depression. Today the drug classes known as SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) are used in the majority of cases of depression due to their ability to increase levels of neurotransmitters such as serotonin and norepinephrine in the brain. Unfortunately, these medications can have severe adverse effects and they don’t even work very well. Almost 50% of people treated for depression do not respond to antidepressant medications (1).
The science emerging from the study of the gut microbiome (the population of tiny microorganisms that live in human intestines) is revealing not only the powerful effect these microbes have on physical health but also the close link between them and our mental health. It has been recognized for centuries that thoughts and emotions have a discernable effect on the function of the gut. Examples of this are “butterflies in the stomach” from nervousness, nausea or diarrhea from performance anxiety and the inability to eat when experiencing stress. But the current revelations surrounding the gut microbiota come from the discovery that the gut can send information back to the brain and these communications can alter the way we think, feel and behave. The longest nerve that originates from the brain is called the vagus nerve. It directly connects the brain to several areas of the gut including the stomach, intestines and pancreas and functions as a two-way communication highway linking the gut microbiome to the brain (2,3). This connected system is known as the “microbiome-gut-brain axis”.
We have become accustomed to hearing that the number of cells in our microbiome is enormous. But do you know how huge it actually is? Amazingly human beings are more microbe than human. In fact only 43% of the cells comprising a human body are human ones. The rest come from the bacteria, viruses, fungi and other single-celled creatures that make up our microbiota. Our human genome, the genetic instructions that make us “human beings”, contains about 26,000 genes but astonishingly our microbiome contains somewhere between two million and 20 million genes with 95% of these located within the gut microbiome (4). It is no wonder that these miniscule “tenants” in our bodies can have such a large influence on us.
Scientists are now recognizing that messages from the gut are being sent to the brain through an intriguing variety of methods. For example…
Gut microbes digest fiber from the food passing through their habitat, our intestines, from which they produce short-chain fatty acids which have the ability to act as signaling molecules that can have widespread effects on many systems of the body (4).
Microorganisms in the gut can produce both hormones and neurotransmitters and they also have the facility to respond to such information-transmitting molecules (4).
Cells in the immune system have receptors that can receive instructions through neurotransmitters produced by gut bacteria, instigating changes in the function of the brain (5).
There is even emerging evidence that gut microorganisms can alter DNA effects in the nervous system by employing small pieces of RNA known as microRNA or mRNA (6).
The earliest hint of this remarkable connection was revealed through a study performed in 2004 in Kyushi, Japan. Researchers showed that “germ-free” mice who had been raised with a complete lack of microorganisms in their guts showed unusual sensitivity to stress. When subjected to a stressful situation these mice produced twice as much of the stress hormones adrenocorticotropin and corticosterone as normal mice (7). From this arose the awareness that the tiny inhabitants in our intestines have far more influence on mammalian bodies than we ever imagined.
The relationship between the Gut Microbiome and Mood
Here is what science has discovered so far.
A healthy microbiome is one composed of a wide range of microbial species and it turns out that our moods depend on the robustness of our microbiome. This is illustrated in people who are experiencing clinical depression by their significantly reduced numbers of gut microbes and the reduced diversity of species compared to a person without depression (8).
There is a high incidence of gastrointestinal problems in people suffering from psychiatric disorders (9).
Any disturbance of the gut microbiota, for example from stress or the use of antibiotics, increases incidence of depression. Antibiotics kill disease-causing microbes but unfortunately can also be fatal to beneficial microorganisms, inducing microbiome-gut-brain axis dysfunction (8).
Studies in both humans and animals have shown that restoring healthy gut microbiota through methods such as the administration of probiotics and/or prebiotics, the transplantation of fecal content from a person with good mental health into a person with depression or even simply eating a healthy diet focusing on whole plant foods relieves depression (8).
Probiotics may work by suppressing cytokines, small proteins that regulate immunity but also can damage the membrane barrier that separates the intestinal contents from the blood vessels that supply oxygen and other nutrients to the brain. Cytokines are released into the gastrointestinal tract due to inflammation caused by microbiome-gut-brain axis dysfunction. Probiotics can reduce this dysfunction thereby decreasing inflammation in the gut (10,11). Multiple randomized, placebo-controlled trials of probiotics have shown that they can be quite effective at decreasing anxiety and depressive symptoms and offer the added bonus of no adverse effects (9).
Probiotics have also been shown to increase the availability of neurotransmitters such as serotonin to the brain (9).
In human/animal studies, depression has been transmitted from depressed human patients to germ-free mice through the transplanting of fecal microbiota. The recipient animals not only developed obvious depressive symptoms but their microbiota numbers and species were also altered significantly (8).
Recent research has found that the antidepressant effects of medications may work not only by their effects on the central nervous system but also by regulation of the microbiome-gut-brain axis (8).
Lifestyles that weaken gut bacteria, for example not eating enough fiber or eating too much saturated fat, sugar and processed foods, destroy normal healthy gut microorganisms and increase incidence of depression (8).
Practical steps towards a healthier microbiome
Eat the high fiber foods that healthy gut bacteria thrive on. Fiber is processed in the gut by these beneficial microbes, producing short-chain fatty acids. The most influential of these short-chain fatty acids is butyrate. It has many positive effects including reduction of inflammation throughout the body, improvement of immune function, promotion of fat burning in muscles cells along with lowered insulin resistance, increases in cancer cell death, discouraging the growth of unfriendly gut bacteria, regulation of mood and the decrease of incidence and severity of chronic diseases (12). Foods highest in fiber include whole grains and lentils (beans, chick peas and lentils), although all whole vegetables and fruits are good sources of fiber.
Eat prebiotic-rich foods. These food choices contain soluble fiber and include onions, garlic, leeks, asparagus, whole wheat, spinach, beans, bananas, oats, soybeans, dandelion greens, chicory root and Jerusalem artichokes. Prebiotics create an optimal habitat for the gut microorganisms that produce butyrate and other short-chain fatty acids (13).
Eat probiotic fermented foods. They contain live bacteria or yeasts that can actually take up residence in the gut, increasing the strength and diversity of the gut microbiome. Healthy probiotic foods include non-dairy yogurt, sauerkraut, tempeh, miso, kimchi and water kefir. Probiotics in pill form are generally not effective for long-term gut health changes (14).
Avoid animal products, especially red meat, dairy and fried foods. All of these inhibit the growth of healthy gut bacteria while encouraging the type of gut bacteria that are linked to chronic diseases. The microbiome can change in a very short time with a change in diet. Studies have found that eating a completely animal-based diet for as little as five days can encourage the overgrowth of microorganisms capable of triggering inflammatory bowel disease (15). On the other hand, switching to a diet high in fiber and complex carbohydrates produces a greater diversity of gut bacteria species, more fiber-eating bacteria, lower markers of inflammation of the colon and a 70% drop in secondary bile acids in only two weeks (16).
Limit fat consumption. Diets high in fat encourage the bacteria that thrive on the bile acids that are needed to digest fat. Unfortunately these same bacteria are associated with development of bowel cancer and inflammatory bowel disease (IBD) (16,17). Eating a whole food carbohydrate-rich diet encourages species of microbes that digest fiber and protect against cancer and IBD (18). Choose healthy fat sources as the ones you do eat. These include nuts, seeds and avocados. Cook with broth, water or wine instead of oil.
Avoid unnecessary antibiotic use. Antibiotics can destroy all kinds of bacteria, both helpful and detrimental. Since 80% of all antibiotic use is in the production of food animals, this is another reason to concentrate your meals on plants (19).
Enjoy moderate exercise every day. Recent studies have shown that athletes have higher diversity in their gut microorganisms (20).
Get plenty of sleep. A study in Sweden showed that as little as two consecutive nights of insufficient sleep begins to damage the microbiome balance, reducing healthy species by almost 50% (21).
Manage stress. It has a major impact on the health of the gut, lowering the number of healthy bacteria and increasing the threat of unhealthy bacteria (22).
It will be fascinating to follow the ongoing gut microbiome research as new discoveries are made. It is the hope of many scientists that our microbes may provide modern medicine with groundbreaking methods for treating not only depression but many other diseases. In fact researchers are already investigating the role of gut microorganisms in cancer, obesity, allergies and other chronic conditions that plague human beings. Though this research is in its infancy, it has already revealed ways in which lifestyle choices can alter our microbial inhabitants. No doubt there is much more to be learned.
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