Bringing microbiome-drug interaction research into the clinic

Abstract

Our understanding of the scope and clinical relevance of gut microbiota metabolism of drugs is limited to relatively few biotransformations targeting a subset of therapeutics. Translating microbiome research into the clinic requires, in part, a mechanistic and predictive understanding of microbiome-drug interactions. This review provides an overview of microbiota chemistry that shapes drug efficacy and toxicity. We discuss experimental and computational approaches that attempt to bridge the gap between basic and clinical microbiome research. We highlight the current landscape of preclinical research focused on identifying microbiome-based biomarkers of patient drug response and we describe clinical trials investigating approaches to modulate the microbiome with the goal of improving drug efficacy and safety. We discuss approaches to aggregate clinical and experimental microbiome features into predictive models and review open questions and future directions toward utilizing the gut microbiome to improve drug safety and efficacy.

Bacterial Vaginosis: Current Diagnostic Avenues and Future Opportunities

“…Another area that may be relevant to investigate in BV is microbiome-drug interactions, more recently termed pharmaco-microbiomics. In pharmaco-microbiomics, individual variation in drug response can be addressed by characterizing the composition of microbial communities and identify the chemical mechanisms in these microbiomes to understand drug metabolism (Guthrie and Kelly, 2019 ). A relationship has already been established between the VMB and levels of antiretrovirals (ARVs), for instance, in women with a VMB consisting of G. vaginalis and other anaerobic bacteria lower levels of tenofovir were detected than in women with a Lactobacillus- dominating microbiome (Donahue Carlson et al, 2017 ; Klatt et al, 2017 ).…”

Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome

“…Traditional standard treatments for autoimmunity have been immunosuppressive medications that dampen the immune system non-specifically and alter the gut microbiome composition (111,112). Furthermore, microbiome-drug interactions also provide mechanistic insight into the role of gut microbiota in drug efficacy and toxicity (113).…”

Model-based prediction of bacterial population dynamics in gastrointestinal infection

“…In recent years the benefit of computational methods to improve patient treatment has been recognized and we know that the efficacy of drug treatment is highly variable between individuals. Numerous host factors, such as the composition of the microbiota, can significantly influence the success of a treatment (Guthrie & Kelly, 2019). Therefore, computational approaches are being developed that integrate available patient data to derive personalized and improved therapy guidelines (Shameer et al, 2015;Toh et al, 2019).…”