The Intestinal Microbiome and Depression: Nutritional Intervention

Several systematic reviews and meta-analyses demonstrate associations between alterations in the composition of the microbiota and various mental disorders such as clinical depression (1, 2, 3). Several factors, including diet, play a crucial role in modulating this link, offering promising opportunities for the treatment and prevention of depression (4).

The Imbalance

When an imbalance of the microbiome occurs, called "dysbiosis," profound repercussions on mental health can be observed. Studies have shown that, compared to healthy subjects, patients with depressive symptoms often exhibit reduced microbial diversity and detrimental changes in bacterial distribution. These alterations are characterized by a relatively higher contribution of pro-inflammatory bacteria, such as those associated with lactic acid production, glutamate metabolism, and gamma-aminobutyric acid (GABA). These changes in the microbiome also involve a reduced proportion of anti-inflammatory bacteria, such as those producing short-chain fatty acids (acetate, propionate, and butyrate) (1, 2, 3).

The Connection Between the Microbiome and Depression

The gut-brain axis allows communication between the gastrointestinal system and the central nervous system. In fact, enteric nerve connections are bidirectional and maintain links with the immune, endocrine, and autonomic nervous systems via the vagus nerve (5). Dysbiosis can therefore disrupt this pathway and lead to or exacerbate mood disorders, such as depression (4, 5). One suggested biological mechanism is the increase in chronic inflammation in the body caused by the imbalance between pro- and anti-inflammatory bacteria (2, 4). For example, short-chain fatty acids, metabolites produced by anti-inflammatory bacteria during the fermentation of dietary fibers, act on anorexigenic enteroendocrine cells. This leads to a decrease in appetite, regulating eating behavior and energy balance. Short-chain fatty acids also affect immune functions by promoting the integrity of the intestinal barrier and modifying cytokine production (6). An increase in inflammation caused by a microbiota imbalance is associated with an increased incidence of depression (7).

Diet and Microbiome

Diet is one of the main modulators of the intestinal microbiome. A diet rich in processed foods, saturated fats, added sugars, sweeteners (especially sucralose), and emulsifiers can promote the proliferation of pro-inflammatory bacteria (8, 9). Conversely, a diet rich in fiber, prebiotics, polyphenols, fish, and fermented foods can promote a healthy and diversified microbiota and is linked to a significant improvement in well-being in individuals with major depression (4, 5, 7, 10). Moreover, evidence from randomized controlled trials has demonstrated favorable outcomes for Mediterranean dietary patterns as a nutritional therapy for reducing chronic inflammation and improving cognitive abilities in the elderly (11) as well as reducing symptoms of moderate to severe anxiety and depression in adults (12, 13).

Probiotics: Potential Allies

Some data suggest that probiotics such as Bifidobacterium infantis, Lactobacillus helveticus, and Lactobacillus rhamnosus may reduce depression-related symptoms (4). These strains help regulate the hypothalamic-pituitary-adrenal axis and normalize cortisol and pro-inflammatory cytokine levels (1). Significant effects of probiotic use have been observed with daily consumption of 10^9 Colony-Forming Units (CFU) over a period of more than 8 weeks (5).

Other Therapeutic Interventions

In addition to diet and probiotics, other factors can influence the link between the microbiome and depression. Physical activity (150 minutes of moderate exercise per week) is notably linked to an increase in beneficial bacteria producing anti-inflammatory metabolites and helps maintain a symbiosis between commensal and pathogenic bacteria (4). Sleep disruption can also alter the composition of the microbiome, thereby worsening depressive symptoms (4).

The role of the microbiota in mental health is undeniable. Although research is still in its early stages, it is clear that nutritional intervention, in collaboration with a nutritionist from TeamNutrition, can offer significant benefits in managing depression. It is essential for medical doctors and healthcare professionals to consider holistic and interdisciplinary approaches to treat depression by integrating diet, probiotic supplementation, and other lifestyle-related interventions. Contact us to learn more about our services.

References 

1. McGuinness, A. J., Davis, J. A., Dawson, S. L., Loughman, A., Collier, F., O’hely, M., ... & Jacka, F. N. (2022). A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia. Molecular psychiatry, 27(4), 1920-1935.
2. Nikolova, V. L., Smith, M. R., Hall, L. J., Cleare, A. J., Stone, J. M., & Young, A. H. (2021). Perturbations in gut microbiota composition in psychiatric disorders: a review and meta-analysis. JAMA psychiatry, 78(12), 1343-1354.
3. Safadi, J. M., Quinton, A. M., Lennox, B. R., Burnet, P. W., & Minichino, A. (2022). Gut dysbiosis in severe mental illness and chronic fatigue: a novel trans-diagnostic construct? A systematic review and meta-analysis. Molecular Psychiatry, 27(1), 141-153.
4. Ghannoum, M. A., Ford, M., Bonomo, R. A., Gamal, A., & McCormick, T. S. (2021). A microbiome-driven approach to combating depression during the COVID-19 pandemic. Frontiers in Nutrition, 8, 576.
5. Dinan, T. G., Stanton, C., Long-Smith, C., Kennedy, P., Cryan, J. F., Cowan, C. S., ... & Sanz, Y. (2019). Feeding melancholic microbes: MyNewGut recommendations on diet and mood. Clinical Nutrition, 38(5), 1995-2001. 
6. Ribeiro, G., Ferri, A., Clarke, G., & Cryan, J. F. (2022). Diet and the microbiota–gut–brain-axis: a primer for clinical nutrition. Current Opinion in Clinical Nutrition and Metabolic Care, 25(6), 443.
7. Radjabzadeh, D., Bosch, J. A., Uitterlinden, A. G., Zwinderman, A. H., Ikram, M. A., van Meurs, J. B., Luik, A. I., Nieuwdorp, M., Lok, A., van Duijn, C. M., Kraaij, R., & Amin, N. (2022). Gut microbiome-wide association study of depressive symptoms. Nature Communications, 13(1).
8. Rodriguez-Palacios, A., Harding, A., Menghini, P., Himmelman, C., Retuerto, M., Nickerson, K. P., ... & Cominelli, F. (2018). The artificial sweetener splenda promotes gut proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohn’s disease–like ileitis. Inflammatory bowel diseases, 24(5), 1005-1020.
9. Noble, E. E., Hsu, T. M., & Kanoski, S. E. (2017). Gut to brain dysbiosis: mechanisms linking western diet consumption, the microbiome, and cognitive impairment. Frontiers in behavioral neuroscience, 9.
10. Lin, K., Li, Y., Toit, E. D., Wendt, L., & Sun, J. (2021). Effects of polyphenol supplementations on improving depression, anxiety, and quality of life in patients with depression. Frontiers in Psychiatry, 12, 765485.
11. Ghosh, T. S., Rampelli, S., Jeffery, I. B., Santoro, A., Neto, M., Capri, M., ... & O'Toole, P. W. (2020). Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut, 69(7), 1218-1228.
12.  Bayes, J., Schloss, J., & Sibbritt, D. (2022). The effect of a Mediterranean diet on the symptoms of depression in young males (the “AMMEND: A Mediterranean Diet in MEN with Depression” study): A randomized controlled trial. The american journal of clinical nutrition, 116(2), 572-580.
13.  Parletta, N., Zarnowiecki, D., Cho, J., Wilson, A., Bogomolova, S., Villani, A., ... & O’Dea, K. (2019). A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutritional neuroscience, 22(7), 474-487.