Mapping the reciprocal interactions between antidepressants and the gut microbiome: novel targets for the personalisation and optimization of drug response.

Nov 19, 2025Molecular psychiatry

How Antidepressants and Gut Bacteria Work Together

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Abstract

Research shows that gut bacteria can affect how well antidepressants work. This study looked at how antidepressants change the types of bacteria in the gut. We found that taking antidepressants increases good bacteria that reduce inflammation and decreases harmful bacteria. The type of bacteria a person has before starting treatment can help predict how well a specific antidepressant will work for them. We also identified certain bacteria that could help improve treatment outcomes. These insights could lead to more personalized antidepressant treatments by considering a person's gut bacteria.

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Although accumulating evidence suggests a role of the gut microbiome in the response to antidepressant medications, its mechanistic basis is largely unknown. We performed a comprehensive analysis and presented an up-to-date atlas of the relationship between antidepressants and gut microbiome. The main findings were: 1. Treatment with antidepressants increases the abundance of anti-inflammatory species (e.g., Bifidobacterium) and decreases that of pro-inflammatory species (e.g., Escherichia_coli); 2. The nature of microbiome at baseline and of its changes following the start of treatment can be used to predict the efficacy of individual antidepressants. 3. Two sets of bacterial taxa (termed "Microhancers" and "Microlencers") are candidate pre-treatment targets for optimizing the therapeutic response. Two mechanisms that appear to underlie the modulation of the antidepressant treatment response are biotransformation and bioaccumulation, and these appear to be mediated by specific bacterial strains. These findings could support the personalisation of treatment by informing the selection of the best antidepressant for each individual. In addition, they suggest that the therapeutic response to antidepressants may be optimised by manipulating the gut microbiome prior to treatment.

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Abstract

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