A recent review, published by assistant professor Suzanne Devkota at Cedars-Sinai Medical Centre in Los Angeles (USA), have shed light on the importance of controlling for external factors in microbiome studies, focusing on medications that could have confounding effects.
Recent research has highlighted the role of the gut microbiome in pharmacology and precision medicine. Although the relationship between the gut microbiota and several human diseases is well known, the role of treatments–including medication and lifestyle interventions–that may confound reported gut composition remain largely underexplored. A study from Forslund et al. was the first to explore whether stratifying for metformin treatment, a widely prescribed antidiabetic drug, affected whether microbial signatures of type 2 diabetes (T2D) were still apparent. Gut microbiota partially mediated both therapeutic and adverse effects of metformin; indeed, untreated patients with T2D showed a decrease in beneficial butyrate-producing bacteria, which was reversed with metformin treatment. The researchers concluded that in T2D patients there is a need to disentangle gut microbiota signatures of disease from those of metformin. Therefore, drug-host-microbiota interactions can contribute to therapeutic and side effects of drug treatments. As drug treatments may be a potential confounder, “patient populations should be stratified for medications when looking for gut microbial signatures of disease”, said Dr. Devkota. Researchers suggest identifying such confounding factors and excluding them at the beginning when prospective studies are performed. However, a limitation is that it is difficult to find enough patients who have not undergone treatment and it is not ethical to exclude patients for taking medication for the purpose of studying drug-microbiome interactions.
In addition to the impact of medications on microbial community structure and function, gut microorganisms can affect drug therapy through pathways that involve the biotransformation of drugs or their metabolites. Thus, further research into drug-microbiome interactions and underlying mechanisms is needed.
To sum up, microbiome research should consider drug therapy effects as they may be a potential confound. Due to the fact that prescription drugs have an impact on the human gut microbiome, the effects of treatment should be disentangled from the effects of specific diseases on the human-associated microbiota.
Devkota S. MICROBIOME. Prescription drugs obscure microbiome analyses. Science. 2016; 351(6272):452-3.
Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015; 528(7581):262-6.