The Microbiota, Chemical Symbiosis, and Human Disease

• Complex symbioses exist between human systems and the microbiota.
• The most intimate contacts between domains of life occur at the mucosal epithelia.
• Three mucosal compartments are considered: the nasal sinuses, lungs, and intestines.
• New opportunities for the rational modulation of the microbiota are reviewed.

Our understanding of mammalian–microbial mutualism has expanded by combing microbial sequencing with evolving molecular and cellular methods, as well as unique model systems. Here, the recent literature linking the microbiota to diseases of three of the key mammalian mucosal epithelial compartments—nasal, lung, and gastrointestinal tract—is reviewed with a focus on new knowledge about the taxa, species, proteins, and chemistry that promote health and impact progression toward disease. The information presented is further organized by specific diseases now associated with the microbiota: Staphylococcus aureus infection and rhinosinusitis in the nasal-sinus mucosa, as well as cystic fibrosis, chronic obstructive pulmonary disorder, and asthma in the pulmonary tissues. For the vast and microbially dynamic gastrointestinal compartment, several disorders are considered, including obesity, atherosclerosis, Crohn's disease, ulcerative colitis, drug toxicity, and even autism. Our appreciation of the chemical symbiosis ongoing between human systems and the microbiota continues to grow and suggests new opportunities for modulating this symbiosis using designed interventions.

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