Approximately 18.4% of US adults report having been diagnosed with depression (CDC, 2023). Dietary intake may account for 30 to 40% of cases (Lassale et al., 2019). Specific nutrients and the gut microbiota affect neurotransmitter production and transmission, inflammation, and oxidative stress and work in complex ways to affect mental health.

Neurotransmitters

Serotonin and dopamine affect mood and motivation respectively and their production relies on Omega-3 fatty acids, vitamin D, vitamins B6, B12, and folate (B9) (Freeman et al., 2006; Firk & Markus, 2009; Miller & Raison, 2016; Bottiglieri, 2005). Vitamins B6 and B12 are additionally essential for the production of norepinephrine, too little of which can bring on depression (Moret & Briley, 2011)

Dietary magnesium and zinc contribute to glutamate and GABA transmission (Murck, 2002; Prasad, 2008). Appropriate balance of these respective excitatory and inhibitory neurotransmitters mitigate depression by regulating anxiety and stabilizing mood (Truong et al., 2021).

A deficiency in the amino acid tryptophan, a precursor for serotonin, can cause depression (Richard et al., 2009). Foods rich in tryptophan include turkey, oats, milk, tuna, chocolate, and banana. Whole plant sources of carbohydrates additionally improve tryptophan uptake in the brain.

Beneficial gut microbes also produce the above neurotransmitters, mitigating depression (Dicks, 2022). These microbes thrive on ingested plant foods high in a compound called inulin found in onion, barley, chicory, and garlic and resistant starch found in nuts, seeds, beans, legumes, and whole grains.

Inflammation

Ultra-processed foods and foods high in refined carbohydrates, saturated fats, and trans fats can cause inflammation and consequently initiate and accelerate depressive symptoms (Lassale et al., 2019). High-sugar diets influence hormones like insulin and cortisol, which affect mood (Goldstein et al., 2020).

Foods high in Omega-3 fatty acids, particularly marine sources, DHA and EPA, diminish inflammation and hence depression (Berk et al., 2013).

A high fiber diet generally supports the growth of beneficial gut bacteria that produce short chain fatty acids (SCFAs). SCFAs reduce inflammation and improve mood (Nagpal et al., 2018).

Oxidative Stress

Free radicals are molecules that take electrons from other molecules. They cause harm when they take electrons from molecules of cells and tissues, including those in the brain. Antioxidants neutralize free radicals. Diets low in antioxidants, found in fruits and vegetables, can increase oxidative stress, which is linked to depression (Berk et al., 2013).

Microbiota-Gut-Brain (MGA) Axis

The gut and brain interact via neural, endocrine (hormonal), immune, and metabolic pathways (Rusch et al., 2023). Gut microbes stimulate the release of peptides (short amino acids chains) and hormones from intestinal linings and, as mentioned above, release other products including short chain fatty acids and neurotransmitters.

The hypothalamic pituitary adrenal (HPA) axis is a system largely involved in the stress response and is central within the MGA axis. An imbalance of gut microbiota (dysbiosis) causes HPA axis dysregulation and increases the stress response contributing to depression (Sudo et al., 2004). A diet high in refined carbohydrate further increases cortisol levels and risk of depression (Goldstein et al., 2020).

Microbial SCFAs can dampen the body’s cortisol induced stress response (Dalile, 2020). Additionally, fermented foods and probiotics increase SCFA production and favorably affect gut microbial composition diminishing depression (Selhub et al., 2014).

Conclusion

A diet rich in nutrients, fiber, and antioxidants enhances neurotransmitter production and function, lowers inflammation, and reduced oxidative stress. Increasing fermented foods and avoiding ultra-processed ones both minimize inflammation and allow beneficial microbes to flourish.

Although the complexity of substances and systems makes identifying discrete mechanisms difficult, the effects of gut microbes on mood and mental health via the microbe-gut-brain (MBA) axis remain indisputable (Appleton, 2018).

Patrick Traynor, PHD, MPH, RD, CPT is a registered dietitian with an insurance-based practice, MNT Scientific in South Lake Tahoe, Sacramento, Minden, and does telehealth. Inquiries and appointments can be made by phone (530)429-7363 email, info@MNTScientific.com or website, MNTScientific.com.