Conrad Li

Background: Major depression disorder (MDD) is a leading cause of disability worldwide. The pathophysiology of MDD is complex and poorly understood with multiple competing theories including HPA axis dysregulation, monoamine deficiency, and chronic neuroinflammation.¹³ Studies over the last couple decades have found links between gut microbiome abnormalities and mental illness.^{3,9,10,12,14,15} However, the exact mechanism behind this correlation is still unknown. Despite recent studies showing that luminal and fecal microbiomes vary significantly, fecal matter transplants (FMT) still remains the most common method to study the gut microbiome.²¹ This review summarizes recent literature characterizing microbiome alterations in MDD and explores the therapeutic efficacy of FMT in mouse models.

Methods: A literature search using PubMed was performed using terms including “MDD”, “gut microbiome,” “fecal matter transplant”, “brain-gut axis,” “short-chain fatty acid”, and “microbiome diversity metrics.” Publications before 2015 were excluded.

Results: Studies have shown that the gut microbiome is essential for maintaining homeostasis. Gut microbiota perform a variety of functions which include digesting complex carbohydrates, synthesizing micronutrients, modulating immune response, and metabolizing bile acids.^1,2,5,6,7,8 The microbiome also exerts direct effects on the brain by producing neurotransmitter precursors, increasing neuroplasticity, and shielding the brain from harmful microbial byproducts.^{3,9,10,12,14,15} While fecal samples vary greatly in microbiota composition even amongst normal individuals, comparative analysis still shows differentially enriched flora between MDD and healthy patients.^4,15 Namely, MDD patients have increased loads of bacteria that are good protein metabolizers and release proinflammatory molecules.¹⁵ On the other hand, healthy patients have microbiota that are better carbohydrate metabolizers, vitamin synthesizers, and neurotransmitter producers.^15,19 Microbial diversity however is not consistently increased or decreased in MDD.¹⁵ Mouse studies have shown that transplantation of fecal samples from MDD patients results in more depressive behaviors relative to samples from healthy patients.^{16,17,18,19,20} However, only two studies incorporated autotransplant, non-intervention, or another equivalent control.^19,20

Conclusions: Current research shows that the microbiomes of healthy and MDD patients have prominent differences. However, future work is still needed to elucidate the mechanisms behind these changes and identify the differentially enriched species. Studies in mice have demonstrated that FMTs from MDD patients induce more depressive symptoms than FMTs from healthy patients. Future experiments should include more rigorous controls to verify if FMTs actually improve MDD-like symptoms over non-intervention. Lastly, new techniques should be developed to noninvasively sample the lumen and epithelium of the GI tract and reduce reliance on fecal samples.

Works Cited:

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