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Depression & the Microbiome

iStock-1445997691Results of a small pilot study published in May 2023 in Neuroscience explored connections between the gut microbiome and depression among young adults. Shotgun metagenomic sequencing was performed on stool samples from 40 young adults with major depressive disorder (MDD) and 42 healthy controls, with results controlled for multiple confounders, including demographics, alcohol or cigarette use, exercise, and bowel characteristics.

Overall, no significant differences in gut microbiome structure were observed between groups, but significant differences in the abundance of the Sutterellaceae family as well as species within the Clostridium, Eubacterium, and Ruminococcus genera were documented. Lastly, an increase in cysteine degradation was more likely in adults with MDD.

This small study supports findings from larger datasets, indicating that differences in the microbiome may be related to depression, with some evidence suggesting a causal relationship. For example, the results of a Mendelian randomization study published in 2022 in the Journal of Affective Disorders suggest a protective effect of some genera, including Actinobacteria, Bifidobacterium, and Ruminococcus, as well as a potentially harmful effect of the Streptococcaceae family. This 2022 analysis had the advantage of using large datasets from publicly available GWAS (genome-wide association studies), as well as the statistical strength of Mendelian randomization, nearly equivalent to a randomized controlled trial in the ability to detect causality and control for confounding factors and reverse causality.

The accelerated degradation of cysteine observed in the small pilot study may be a novel finding. Certainly, excessive oxidative stress and mitochondrial dysfunction have been associated with depression, as well as evidence from a systematic review and meta-analysis that N-acetylcysteine may improve depressive symptoms.

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