Further Evidence for the Role of Probiotics in Depression

Recent scientific research has been uncovering the intestinal microbiome’s impact on the nervous system’s development and functioning. The gut microbiome and specific neurobiological pathways are known as the “microbiome-gut-brain axis.”

There are two main paths through which information can flow in the microbiome-gut-brain axis: top-down or bottom-up. The top-down path is when information travels from the brain (through experiences, for example) and influences intestinal microbiota composition. Conversely, information can also journey from the intestine and affect the nervous system in a bottom-up approach.

Using the bottom-up method, scientists have shown that altering the intestinal microbiota composition makes it possible to influence behavior and address several pathological alterations in the brain. Furthermore, these studies have contributed to how we now view microbes as a source of disease and a potential cause of health.1

Several research groups have studied the use of specific probiotic formulations to improve human mental health worldwide. Studies involving the microbiome are difficult due to the immense variability in human microbiome composition.2 Nonetheless, a recent clinical trial conducted by a team from the University of Basel and the University of Leuven demonstrated that, after four weeks of treatment, patients receiving the probiotic had fewer depressive symptoms than those assigned to placebo, highlighting the role of microbiota in mental health.3

In this study, patients with current depressive episodes were recruited from the University Psychiatric Clinics Basel, Switzerland, and randomly assigned to receive the De Simone Formulation (under the trademark Vivomixx in the EU), 900 billion live bacteria daily, or a matching placebo for 31 days in addition to their antidepressant medication. Neither the study participants nor the study staff knew whether the patients were taking probiotics or placebo. The researchers analyzed the differences in a clinical scale used to measure depression, called the Hamilton Rating Scale for Depression (HAM-D), from baseline to the end of treatment and again when four weeks had passed from the end of treatment.

The results showed that when patients took their study treatment as indicated, those in the probiotic group had fewer depressive symptoms than those in the placebo group. After analyzing stool samples from the participants, the researchers found that probiotic-treated patients had more Lactobacillus species in their gut microbiome than placebo-treated patients, which was, in turn, associated with fewer depressive symptoms.

Brain imaging of the participants who took probiotics revealed decreased neural activity in the putamen, a region involved in emotional processing and associated with depression. In subsequent analyses, the researchers studied the brain function and blood perfusion of the supplemented patients using neuroimaging techniques such as functional MRI.4 They found that patients who received a placebo had the typical brain alterations associated with depression. In contrast, those who received the probiotic had signs of preserved structural integrity and fewer signs of neurodegeneration. These findings were accompanied by improvement in depressive symptoms, prompting the authors to presume that the beneficial clinical effects of probiotic supplementation in depression may be due to a protective effect against neuronal degeneration.4

As a part of their clinical trial, the investigators examined if there were probiotic-induced changes in episodic memory.5 For this, they performed the verbal learning and memory test  (VLMT) and three other cognitive tests to the trial participants before and immediately after the treatment. The baseline assessment showed no difference in the VLMT score between groups. However, after treatment, the probiotic group performed better in the VLMT test, indicating a significantly improved immediate recall after four weeks of probiotic supplementation. The other cognitive tests did not reveal significant changes, which may have been due to the relatively short intervention time, or because probiotics may affect cognition in a domain-specific way. Brain imaging during a working memory task showed that the left hippocampus was less activated in probiotic-treated patients and more activated in placebo-treated patients after the four weeks of treatment. Since the hippocampus appears hyperactive in patients with depressive symptoms, this activation pattern supports the beneficial clinical effects observed in the probiotic group.

The clinical trial conducted by the Basel and Leuven Universities and the following analyses support the role of the microbiome-gut-brain axis in treating depression. The findings also emphasize the potential of using specific combinations of probiotics as an accessible and effective add-on therapy to current antidepressant treatments, paving the way for more effective strategies for this debilitating condition.

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  1. Bastiaanssen TFS, Cowan CSM, Claesson MJ, Dinan TG, Cryan JF. Making Sense of … the Microbiome in Psychiatry. International Journal of Neuropsychopharmacology. 2018;22(1):37-52. doi:10.1093/ijnp/pyy067
  2. Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R. Current understanding of the human microbiome. Nat Med. Apr 10 2018;24(4):392-400. doi:10.1038/nm.4517
  3. Schaub A-C, Schneider E, Vazquez-Castellanos JF, et al. Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial. Translational Psychiatry. 2022/06/03 2022;12(1):227. doi:10.1038/s41398-022-01977-z
  4. Yamanbaeva G, Schaub A-C, Schneider E, et al. Effects of a probiotic add-on treatment on fronto-limbic brain structure, function, and perfusion in depression: Secondary neuroimaging findings of a randomized controlled trial. Journal of Affective Disorders. 2023/03/01/ 2023;324:529-538. doi:https://doi.org/10.1016/j.jad.2022.12.142
  5. Schneider E, Doll JPK, Schweinfurth N, et al. Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial. Journal of Psychiatry and Neuroscience. 2023;48(1):E23-E33. doi:10.1503/jpn.220117

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