Depression is a complex mental health disorder that affects individuals and society on a large scale. It is the second-most leading cause of disabilities globally. The economic burden of major depressive disorder (MDD) in adults in the US was $210.5 billion in 2010. There are 17.3 million adults (6.8%) and 3.2 million adolescents (13.3%) in the United States who have experienced at least one major depressive episode in 2017. Current research explores the link between depression and the gut microbiome. 

Gut microbiome dysbiosis has been linked to antibiotic use, diets high in sugar, and environmental factors such as toxin exposure and social stressors. In animal studies, chronic exposure to antibiotics led to a decrease in the diversity and richness of the gut microbiome. This coincided with observations in depressive-like behaviors and altered levels of compounds integral to neurotransmitter systems such as 5-hydroxytryptamine (5-HT), levodopa, and dysregulation in monoamine synthesis and degradation.

The composition of taxa within the microbiome may have a direct influence on mood. Elevated levels of bile acids have been linked to stimulation of the farnesoid X receptor, which attenuates the production of the brain-derived neurotrophic factor (BDNF). The BDNF is a protein that plays an important role in synaptic plasticity, nervous system modulation, memory formation, and the growth, maintenance, and survival of neurons. Decreased BDNF levels have been observed in studies involving major depressive disorders. Bifidobacteria plays a role in bile salt hydrolyzation and some strains of Eggerthella facilitate bile acid oxidation, which may help maintain BDNF levels. In a study exploring the role of Bifidobacterium in depression, Bifidobacterium was shown to decrease serum corticosterone levels and reverse deficiencies in 5-HT and BDNF.

A randomized double-blind placebo-controlled study assessed the effects of supplementation with Lactobacillus plantarum on stress and related biomarkers. This 12-week long study showed significant reductions in stress and anxiety scores using the Depression Anxiety Stress Scales (DASS-42). A reduction in stress scores was observed as early as week 4. When compared to the placebo, the treatment arm showed significant improvement in self-reported stress. Lower plasma proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha (TNF-α) levels and changes in cortisol levels were observed in the treatment arm. In other studies investigating proinflammatory biomarker levels in depression, there were significantly increased levels of interleukin-6 (IL-6), IL-8, TNF-α, and C-reactive protein observed.

Short-chain fatty acids (SCFAs) are produced by bacteria from dietary fiber in the gut microbiome. A study assessed the levels of SCFAs in individuals experiencing depression and those who had an absence of depression. Non-depressed persons had generally higher levels of SCFAs. Of note, the SCFA isocaproic acid was elevated in the group with depression. Fiber consumption was also investigated by using questionnaires and food diaries. The study noted that individuals who had depression did ingest less fiber, but the results were not significant, and the fiber intake did not correlate with SCFA levels.

The link between the microbiome and depression is still being richly explored in pharmacological research. Current research indicates that the gut-brain axis merits consideration from a clinical perspective. Dietary changes and supplementation with probiotics may influence the gut-brain connection and support a healthy mood.

By Colleen Ambrose, ND, MAT