When most of us think about mental health, or we find ourselves pinned by its gravity, we generally think more about our brains than about our guts. Maybe we should think again.

The World Health Organization has declared depression the single largest contributor to disability worldwide, yet currently available treatments are able to induce remission less than 50% of the time. At the same time, more and more data suggests a repeated link between diet quality, gut microbiota, and susceptibility to a variety of mental health ailments, independent from other risk factors. The nascent field of nutritional psychiatry acknowledges the sizable gap between our current treatments for mental health conditions and offers a hopeful other way: adjusting our diet.

This does not suggest that pharmaceutical or psychological interventions should be abandoned. Quite the opposite: mental health is multifactorial, and often requires multimodal therapy. The emergence of adjusting diet as a preventative strategy or possible intervention for depression, anxiety or other mental health disorders should not replace standard therapies. Although our brain creates our emotional and intellectual experience, it can be helpful to remember that it is also an organ with needs for nourishment and care, just like our heart or our liver. The brain, too, is sensitive to its environment.

Scientists are beginning to learn that mental health disorders share an important underlying cause with many other more “somatic” diseases, such as heart disease or diabetes: systemic inflammation.

Links Between Inflammation in the Gut and Mental State

The paradigm of mental health disorders as inflammatory disease is still emerging but is gaining support. One recent human study showed that a spike in the pro-inflammatory cytokine IL-6 in the CSF could produce depressive symptoms in men. Another study in patients with major depression found that higher depressive symptoms were associated both with higher circulating C-reactive protein (CRP), an inflammatory marker, and a lower abundance of the anti-inflammatory cytokine IL-10. Additionally, immune-suppressing medications used to treat autoimmune conditions such as inflammatory bowel disease reduced depressive symptoms both in humans and in animal models.

It may not seem obvious, but the gut is actually the largest immune organ in the body. The surface area of the intestine (called the epithelium)—where our body interfaces with the outside world—could cover half a badminton court. Underneath that surface is a diverse network of immune cells, poised to sample the periphery and maintain order. Above the protective mucus layer that tops the epithelial surface sits the body’s largest collection of friendly (and occasionally unfriendly) microbes. The gut microbiota (as it is called) partners with us for important physiological functions including facilitating our metabolism, helping to reinforce the stability of the gut’s epithelial barrier, providing nourishment for the intestinal cells, and even producing neurotransmitters.

The gut microbiota is directly affected by the food we eat, as our food is ultimately its food. Our gut microbiota, in turn, affects our inflammatory state by breaking our food down into compounds that modify immune cells. So when we talk about diet, we are really talking about an entire downstream cascade of events which can manifest in poor health status when imbalanced. That imbalance can also affect our minds.

To date, several human studies have observed the reduced risk for depression in diets higher in fruits and vegetables, fish, whole grains and olive oil. People who suffer from diabetes, a strongly diet-influenced disease, are twice as likely to also suffer from depression, and also more likely to have anxiety. There is also a notable comorbidity between people who suffer from heart disease and depression. People treated for major depression using personalized dietary counseling and support were 4 times more likely to experience remission than a social support group alone (32% and 8% remission respectively). Moreover, transplanting the gut microbiota from depressed humans into rats was enough to produce depressive and anxiety-like behavior in the rodents, suggesting that the gut is an important bioreactor for mind-altering microbes.

Several specific nutritional components may have an important impact on the microbiota and the mind. It’s worth noting that a variety of dietary interventions for depression have not shown success, but of those that have, a common thread among many is the emphasis on fruits, vegetables, fiber, and whole grains. While somatic conditions like heart disease and diabetes each have clinically supported diets, it is not yet common practice to prescribe dietary intervention for mental health disorders.

For brevity’s sake, we are not able to entertain a comprehensive list of the nutrients that have been potentially linked to mental health, or to explore their role in a broader variety of mental health conditions. However, we will discuss several dietary components and the evidence that supports a possible role in promoting better mental health, especially with regard to depression and anxiety.

The Role of Fiber (AKA Prebiotics) in the Gut Microbiota

Fiber is composed of the indigestible polysaccharides that serve as roughage in our diet, and can be found in fruits and vegetables, beans, seeds and whole grains. These polysaccharides are a key food source for many healthy bacteria in the intestine. The American diet is notoriously low in fiber on average (only 5% consume the recommended amount, 19-38g per day). Fiber is important; though we can’t break it down ourselves, fiber is broken down by the microbiota into short-chain fatty acids (SCFA), which are arguably the heroes of homeostasis—or balance—in the gut. Not all bacteria are able to metabolize fiber into SCFA, only certain microbes, such as Faecalibacterium prauznitzii or members of the bacterial families Lachnospiraceae and Ruminococcaceae. Fiber feeds these bacteria that produce the SCFA by giving them the stable food source they need to grow and persist.

 

SCFA affect many aspects of health, including the following:

• They serve as the primary energy source for colon epithelial cells.
• They fortify the tight junctions that keep the intestinal barrier strong.
• They promote the production of the healthy intestinal mucus that keeps bacteria a safe distance away from the epithelium and underlying immune system.
• They promote pH balance at the epithelial surface by increasing expression of intestinal transporters.
  • This produces the acidic pH favorable to other fiber-fermenting organisms.
  • May help prevent the colonization of infectious organisms, which tend to prefer a slightly higher pH.
• They directly dampen inflammatory response in dendritic cells, macrophages and activated T cells.
• They promote the development of tolerant immune cells.

Higher fiber intake from fruits and vegetables, which is broken down into SCFA by the microbiota, is associated with lower rates of depression in a Japanese population. Other literature reviews concluded that diets rich in nutrients including fiber are linked to a reduced risk for inflammation, depression and anxiety. Both fiber and SCFA directly can also protect against the effects of a model of sickness that induces depressive behavior, such as social withdrawal, in animal models.

Since the effects of fiber are mediated almost entirely by our gut microbiota, it’s important that we consume fiber consistently to support the populations of microorganisms that survive by breaking it down. Low or inconsistent consumption of fiber may not have reliable effects, since those microbes may not persist in a gut ecosystem that does not favor them.

The Role of Antioxidants & Phytonutrients in the Gut Microbiota

Antioxidants are substances that scavenge harmful oxidative substances in our bodies, which can cause cellular damage. The dark greens, reds, blues, purples, oranges, and yellows of different fruits and vegetables indicate the presence of important antioxidants and vitamins that may also positively impact the microbiota, and also have some mental health benefit. Oxidative stress, caused by reactive oxygen species (ROS) or free radicals, can activate the pro-inflammatory cascade, including IL-6 and CRP, which are both associated with depression. Moreover, oxidative damage has been linked to the severity of different mental disorders.

Several antioxidants have been found to either directly dampen depressive symptoms, or are associated with a lower incidence of depression:

• Carotenoids - Yellow and orange-hued compounds found in fruits and veggies such as tomatoes, carrots, oranges, grapefruits, or apricots.
• Curcumin - A compound found in the spice turmeric that is readily metabolized by the microbiota, acting as a potent antioxidant, a prebiotic and antidepressant.
• Ascorbic acid (vitamin C) - A vitamin and powerful antioxidant abundant in many fruits and vegetables.
• Polyphenols such as flavonoids - Micronutrients abundant in tea, citrus, legumes and others.

Flavonoids improved mood in a cohort of young people, and have been shown to improve memory and cognition among the elderly. Many studies have observed the association between a lack of peripheral zinc and depressive symptoms, as well as neurodegenerative diseases. Similarly, low dietary selenium was predictive of developing de novo depression in a prospective study. Deficiency of B vitamins such as folate (B9) and B12, which are derived by the diet and produced by the microbiota, are also associated with treatment-resistant depression.

Fresh fruits and vegetables are bursting with many of these antioxidants and phytonutrients, which makes their health benefits manifold, considering their coincident content of fiber as well. Many antioxidants are also metabolized by the gut microbiota, as microbes in the gut help modulate their bioavailability. On the other hand, oxidative stress from a high-fat low-nutrient diet was associated with reduced diversity and greater numbers of potential pathogens in the microbiota. If this is true, then a low-antioxidant diet is a double loss, both from the loss of the phytonutrients themselves and also from the suppression of a microbial population able to make them bioavailable. Note: it is recommended to get vitamins and antioxidants from food rather than supplementation, since fresh foods deliver a broad diversity of nutrients and fiber at once, and in the biological packaging your body is adapted to receive.

The Role of Probiotics in the Gut Microbiota

Evidence suggests that probiotics may have important mental health benefits, even if their actual passage through the intestine may be transient. Although results have been mixed, some argue that probiotics may be able to mitigate the neurological inflammation central to many mental health disorders. Some probiotic foods promote a stable colonic microenvironment and protect against opportunistic infection in the intestine, which may give them an indirect effect on mental health. One meta-analysis concluded that probiotic intervention was associated with reduced depressive score in people under 60. One animal study showed that a single probiotic strain (Lactobacillus reuteri 3) protected mice from depression associated with social defeat, which may have implications for the far-reaching effect of our guts over our felt experiences.

One important note about probiotics is their method of delivery. In the United States, the Food and Drug Administration (FDA) currently does not regulate the production of commercial probiotic supplements, leaving them vulnerable to variability and inefficacy. For this reason, many recommend fermented foods that contain live cultures in their place. Although fermented foods are more ambiguous with regard to species representation and actual dosage, they contain micronutrients absent in supplements. Consumption of fermented foods has been associated with decreased social anxiety, lower risk of depression, and altered function in brain regions that process emotion in humans, as well as reduced stress in animal models. Admittedly, many more studies are merited to flesh out these claims and to establish meaningful treatment guidelines.

How Can My Diet Promote Mental Health?

Although there may one day be an elegantly developed “depression diet” with precise clinical recommendations, a good research-supported shorthand for now may be:

• Eat your fiber, and eat colorful fruits and vegetables. If nothing else changes in your diet, bolstering your intake of colorful plant-based foods that are high in fiber and antioxidants may be a boost for your gut microbes and your brain.
• Try to reach the recommended 19-38g fiber per day. You may be surprised how much intentionality this takes! Eating with this goal in mind may naturally crowd out some of the less-healthy temptations with satiating foods.
• Small changes matter. Simple additions like throwing chia seeds and some berries on your yogurt or snacking on dates instead of a pastry can have real impacts on your daily fiber intake. No change is too small. The handful of nutrient-rich berries or nuts you eat is better than the home-cooked organic meal you don’t.
• Remember: you’re building an ecosystem. And ecosystems take time. Think of strengthening your gut like reforesting an area. Consistency and time are key ingredients.

Microbes and Mental Health: Concluding Thoughts

When you walk into the doctor’s office with cardiovascular disease or diabetes, it's normal to discuss what you eat. That clinical precedent has not yet been established with mental health, but it may become part of mental health check-ups of the future. The more we understand pathologies as expressions of inflammation that is out of equilibrium, the more logical it becomes to intervene not just with the pathology, but with the entire physiological system. One of the primary ways we have within our power to do that is through the diet.

The manifold connections between the gut microbiota and the brain have emerged in recent years, leading to an exciting area of research both in the prevention and the treatment of disease. Harnessing our diets for the cultivation of our microbes, and in turn our mental and physical health, may well be the next medical frontier.

Further Information:

• Nutritional Psychiatry: The Current State of the Evidence.
• Novel Therapeutic Targets in Depression and Anxiety: Antioxidants as a Candidate Treatment.
• Phytonutrients: Paint Your Palette With the Colors of the Rainbow.
• Podcast: Microbiome Diversity and Structural Variation with Ami Bhatt.

---

The above represent the views of the author and does not necessarily reflect the opinion of the American Society for Microbiology.