Molecular commensalism—how to investigate underappreciated health-associated polymicrobial communities

ABSTRACT The study of human commensal bacteria began with the first observation of prokaryotes >340 years ago. Since then, the study of human-associated microbes has been justifiably biased toward the study of infectious pathogens. However, the role of commensal microbes has in recent years begun to be understood with some appreciation of them as potential protectors of host health rather than bystanders. As our understanding of these valuable microbes grows, it highlights how much more remains to be learned about them and their roles in maintaining health. We note here that a thorough framework for the study of commensals, both in vivo and in vitro is overall lacking compared to well-developed methodologies for pathogens. The modification and application of methods for the study of pathogens can work well for the study of commensals but is not alone sufficient to properly characterize their relationships. This is because commensals live in homeostasis with the host and within complex communities. One difficulty is determining which commensals have a quantifiable impact on community structure and stability as well as host health, vs benign microbes that may indeed serve only as bystanders. Human microbiomes are composed of bacteria, archaea, fungi, and viruses. This review focuses particularly on oral bacteria, yet many of the principles of commensal impacts on host health observed in the mouth can translate well to other host sites. Here, we discuss the value of commensals, the shortcomings involved in model systems for their study, and some of the more notable impacts they have upon not only each other but host health.