Impact of antidepressants on the composition of the gut microbiome: A systematic review and meta-analysis of in vivo studies

Background: There is a growing body of evidence suggesting that antidepressant drugs (ADs) alter the gut microbiome of persons with depressive disorders. Herein, we aim to investigate the gut microbial profile of AD-treated animal models of depression (MoD) and persons with major depressive disorder (MDD).

Methods: We conducted a systematic review and meta-analysis investigating the gut microbiome community-level diversity and relative abundance of microbial taxa in AD-treated animal MoD and persons with MDD.

Results: 24 human studies (898 participants) and 48 animal studies (849 subjects) were identified. Nonsignificant differences in gut microbial richness were observed between AD-treated and nonmedicated animals and humans. Beta diversity analysis in animals shows that AD intake is linked to a distinct gut microbial profile, a result not observed in humans. Consistent depletion of the genera Faecalibacterium and Parasutterella, along with enrichment of Bifidobacterium, was observed in AD-treated persons with MDD. In AD-treated animals, AD intake was associated with depletion of Flavobacterium and Adlercreutzia, and enrichment of Parabacteroides.

Limitations: The studies in our review were heterogeneous in their participant population, dietary intake, type of ADs used, length and dosing of AD treatment, and frequency and time of fecal sample collection.

Conclusion: ADs are associated with some changes to the gut microbiome. Future studies should evaluate the gut microbiome profiles between depressive disorder diagnoses that may reveal potential differences and predictors of AD response, as well as new combinatorial therapeutics with agents (e.g., specific-strain probiotic adjunctive treatment) that can ameliorate micro-composition gut dysbiosis.