LAUSR

Humans and other animals have coevolved with microbes that colonize the epithelia that covers the body’s surfaces, both outside (the skin) and inside (the invaginations and gut). As such, the composite of a vertebrate’s cells and inhabiting microbes are coined “holobiont,” meaning assemblages of different species that form ecological units (Bordenstein & Theis, 2015; Zrzavy & Skala, 1993). The immune system coevolved with the microbiota, collectively limiting microbial colonization to maintain quasisterility in the internal organs. When microbes do penetrate epithelial barriers (eg, through macroor micro-wounds) they trigger immunological responses. Furthermore, immune system failure to restrict the population growth of (even beneficial) microbes can lead to aberrant microbial growth. For example, overgrowth of Candida occurs after immune depression from radiation or chemotherapy. Microbes may also invade forbidden territories under these circumstances, leading to negative outcomes such as sepsis. It is a relatively recent discovery—with the arrival of new nucleic acid sequencing technologies—that human physiology depends on the interactions between our bodies and our coevolved microbes (microbiota), their genes (microbiome), and gene products (metabolome). The health of an individual depends on prenatal and postnatal factors, from the microbiota of the pregnant mother that may affect fetal development, to birth and postnatal exposure, to microbes that program the immune and metabolic systems and modulate development across the human life course. The immune system of humans living in urban centers has become increasingly dysfunctional over the last seven decades, with a concurrent increase in chronic disorders, such as asthma, type 1 diabetes, allergies, and obesity. These modern diseases are also associated with early-life antibiotic exposure (Clausen et al., 2016; Cox & Blaser, 2013; Cox & Blaser, 2015) and C-section birthing (Goldani et al., 2011; Martinez et al. 2017; Rusconi et al., 2017; Tamburini et al., 2016), suggesting a connection with aberrant microbiota development. This would imply that these early-life factors, which influence the microbiome, are involved in the etiology of these modern diseases.