Confounder or Confederate? The Interactions Between Drugs and the Gut Microbiome in Psychiatric and Neurological Diseases.

The gut microbiome is emerging as an important factor in signaling along the gut-brain axis. The intimate physiological connection between the gut and the brain allows perturbations in the microbiome to be directly transmitted to the central nervous system and thereby contribute to psychiatric and neurological diseases. Common microbiome perturbations result from the ingestion of xenobiotic compounds including pharmaceuticals such as psychotropic drugs. In recent years, a variety of interactions between these drug classes and the gut microbiome have been reported, ranging from direct inhibitory effects on gut bacteria to microbiome-mediated drug degradation or sequestration. Consequently, the microbiome may play a critical role in influencing the intensity, duration, and onset of therapeutic effects, as well as in influencing the side effects that patients may experience. Furthermore, because the composition of the microbiome varies from person to person, the microbiome may contribute to the frequently observed interpersonal differences in the response to these drugs. In this review, we first summarize the known interactions between xenobiotics and the gut microbiome. Then, for psychopharmaceuticals, we address the question of whether these interactions with gut bacteria are irrelevant for the host (i.e., merely confounding factors in metagenomic analyses) or whether they may even have therapeutic or adverse effects.