Understanding and modulating mammalian-microbial communication for improved human health.

The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses impacting inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy.