Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota

The gut microbiota contributes to diverse aspects of host physiology, ranging from immunomodulation to drug metabolism. Changes in the gut microbiota composition are associated with various diseases as well as with the response to medications. It is therefore important to understand how different lifestyle and environmental factors shape gut microbiota composition. Beyond the commonly considered factor of diet, small-molecule drugs have recently been identified as major effectors of the microbiota composition. Other xenobiotics, such as environmental or chemical pollutants, can also impact gut bacterial communities. Here, we review the mechanisms of interactions between gut bacteria and antibiotics, host-targeted drugs, natural food compounds, food additives and environmental pollutants. While xenobiotics can impact bacterial growth and metabolism, bacteria in turn can bioaccumulate or chemically modify these compounds. These reciprocal interactions can manifest in complex xenobiotic-microbiota-host relationships. Our Review highlights the need to study mechanisms underlying interactions with pollutants and food additives towards deciphering the dynamics and evolution of the gut microbiota.