Innovative Approach for Depression Treatment: Two Ways of Modifying the Gut-Microbiome to Treat Major Depressive Disorder

Depression is a debilitating disorder that affects people worldwide. However, at least one third of patients do not respond to existing therapies, and novel treatment methods are necessary. A promising new approach for treating depression targets the microbiota-gut-brain axis, which is linked to physiological, behavioral, and cognitive functions affected in major depressive disorder.
Probiotics and fecal microbiota transplantation are two possible ways to modify the microbiota-gut-brain axis.
The first study in this thesis (Doll et al., 2022) presents two patients with diagnosed depression treated with fecal microbiota transplantation as an add-on therapy. Depressive symptoms decreased for both patients four weeks after the transplantation, with the effects lasting up to eight weeks in one patient. Gastrointestinal symptoms were reflected in microbiota changes and improved in one patient.
In the second study (Schaub et al., 2022), we examined the effect of a probiotic
supplementation on depressive symptoms, the gut microbiota, and the brain in a randomized controlled trial. Depressive symptoms decreased over time in both groups, but the decrease was stronger in the probiotic group. Probiotics increased the abundance of the genus Lactobacillus, which was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic
intervention.
In the third study (Schneider et al., submitted), we investigated the effect of the probiotic supplementation on cognitive functions, brain-derived neurotrophic factor, and the brain. We found a significantly improved immediate recall for the probiotics group immediately after intervention and a trend for a time-group-interaction considering all timepoints. We also found a time-group-interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. However, we did not find significant changes of brain-derived neurotrophic factor.
The results of the three studies highlight the role of the microbiota-gut-brain axis in depression and emphasize the potential of adjuvant microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies for depression. Nonetheless, the safety issues of fecal microbiota transplantation and the modest sample size of our studies imply that large-scale studies are needed to better understand the underlying mechanisms of depression and the
microbiota-gut-brain axis and to replicate and validate our results.