Throughout the world, major depression is a leading cause of disability, suffering, and death due to suicide. Although effective treatments for depression exist, about one third of patients do not fully respond to treatment with antidepressant medication. Current research suggests that gut microbiota may play a role in the pathophysiology of depression for some people. Microbiota refers to naturally occurring bacteria, fungi, and other microorganisms in the body. The human gut harbors 100 trillion bacteria that support human health. Gut microbiota can impact various systems within the body, including the central nervous system, which is made up of the brain and spinal cord. Probiotics (beneficial microorganisms) have been shown to produce chemical messengers, such as serotonin and dopamine. These chemical messengers are associated with mood and cognition, and are frequent targets of antidepressant medications.
What does the current research suggest about the microbiome and depression?
Multiple animal studies have linked depressive behavior in rodents to altered gut microbiota, use of antibiotics, and gastrointestinal infections. Depressive behavior in rodents has been observed following fecal transplants from humans with depression. In addition, several studies show differences in the microbiota of depressed people versus non-depressed people. Because of these observations, researchers are exploring how probiotics impact mood in humans. Certain probiotics may be on the horizon as a potential treatments for depression and other neuropsychiatric disorders.
At this time, only a few published studies have examined whether probiotic supplements can help treat depression. When reviewing research studies, it is important to note a few things:
Was the study conducted on a large group of people?
Was the study randominzed, double-blind, and placebo-controlled?
Have the study results been replicated across multiple studies?
Do the researchers have any financial interest related to the study?
Thus far, I found one recently published trial that directly investigates probiotic supplementation and depression. It was randomized, double-blind, and placebo-controlled. However, it only involved 40 adult patients with major depressive disorder. An improvement in depression was observed 8 weeks after probiotic supplementation in the treatment group. The supplements included Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum. This study also demonstrated a decrease in inflammatory markers in the subjects taking the supplement. Although the findings suggest that probiotics can decrease depressive symptoms, potentially be decreasing inflammation, it is only one trial, and the sample size was small.
Additionally, a small pilot study showed a clinically statistical decrease in depressive symptoms in subjects with treatment resistant major depressive disorder who took probiotics. These subjects were already taking antidepressants at the start of the trial, but had a history of poor response to medication. They were given probiotics for 8 weeks, as well as magnesium oxalate. This study was small and was not double -blind , so the results need to be replicated in a larger, more rigorous trial. Furthermore, probiotics were not the only intervention studied in this trial, therefore, the decrease in depression may be due to magnesium supplementation, probiotics, or both.
Finally, there are a few other studies that explore the relationship between mood and probiotics. These studies were conducted on healthy volunteers, and not people with clinical depression. These studies suggest that probiotics may impact mood in healthy subjects. For example, one double- blind, placebo-controlled study showed less psychological distress after 30 days of probiotic treatment (B. logum R0175 and Lactobacillus helveticus). One triple- blind, placebo-controlled, randomized study showed reduction in negative rumination and aggressive thoughts in healthy subjects treated with probioticcs (multi strain Lactobacillus and Bifidobacterium strains). Again, this may not apply to depressed patients, as the participants did not have major depressive disorder.
What can be concluded from the research?
Although the above studies are interesting, they do not yet provide specific treatment recommendations for probiotics and depression. Ideally, consistent results across multiple, well conducted trials should be seen prior to recommending any particular treatment for depression. The exact probiotic strains, dose, length of treatment, and appropriate patient populations are not clearly defined. That being said, certain lifestyle factors have been shown to support both brain AND gut health, and would be reasonable recommendations for those who struggle with depression. Good sleep, quality nutrition, and regular exercise are lifestyle factors that have been shown to improve mood and support a healthy microbiome. Supplementation with probiotics is also an option, however, caution is advised if you suffer form a compromised immune system. Always check with your doctor to see if probiotic supplementation is safe for you.
Selected References:
1. Ait-Belgnaoui A. et. al. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil. 2014 Apr; 26(4):510-20.
2. Akkasheh G. et.al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition. 2016 Mar;32(3):315-20.
3. Bambling M. et. al. A combination of probiotics and magnesium orotate attenuate depression in a small SSRI resistant cohort: an intestinal anti-inflammatory response is suggested. Inflammopharmacology. 2017 Apr;25(2):271-274.
4. Foster, J. et. al. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiol Stress. 2017 Dec; 7: 124–136.
5. Messaoudi M. et. al. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011 Jul-Aug;2(4):256-61.
6. Noble, E. et. al. Gut to brain dysbiosis: mechanisms linking western diet consumption, the microbiome, and cognitive impairment. Front. Behav. Neurosci. 2017, 11,9.
7. Steenbergen L. et. al. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015 Aug;48:258-64.
8. Valles-Colomer M. et. al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019; Feb 4.
9. Wallace, C. and Milev, R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry. 2017; 16: 14.
10. Wang, Y. and Kasper, L. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014 May;38:1-12.
11. Yano, J. et. al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015 April 9; 161(2): 264–276.