Chapter 6: The Gastrointestinal Microbiome and Drug Response

ABBREVIATIONS

THE HUMAN MICROBIOME

What Is It?

The microbiome is the genetic repertoire of the ecosystem of microbes (bacteria, viruses including phages, and sometimes archaea, fungi, and microbial eukaryotes) that coexist at a given site within each human. The human microbiota consists of the collection of microbes that exist in a specific area within the body, such as the oral cavity, esophagus, skin, gut, vagina, and other sites. The composition, regulation, and dynamics of the microbiomes and microbiota inhabiting these body areas are individualized and compartmentalized. The organisms in the oral cavity and gut are more diverse than those in other body sites (Costello et al., 2009; Human Microbiome Project Consortium, 2012). Establishment of the microbiome begins at delivery, with the infant inheriting microbes from the mother and the environment. The mode of delivery affects the infants’ microbial colonization, with babies born via cesarean section dominated by epidermal bacterial species with predisposition to asthma and allergies later in life (Bager et al., 2008; Dominguez-Bello et al., 2010). After the child is weaned, the microbiome is established with an individual signature that persists long term (Faith et al., 2013), possibly throughout life (Maynard et al., 2012). Genes from the microbiome far outnumber human genes, with estimates of over 200 million microbial genes compared to 20,000 human germline genes (Qin et al., 2010). Microbial cells (mainly gut bacteria), on the other hand, are in approximately 1:1 ratio with human cells (Sender et al., 2016). Although an individual’s microbiome appears to be generally stable over that individual’s lifetime, numerous environmental factors can alter the microbial composition, including geographic location, diet, lifestyle, and xenobiotics (Human Microbiome Project Consortium, 2012; Kaplan et al., 2019; Kurilshikov et al., 2021). Other influences include circadian rhythms, age, and season of the year.

More than 90% of the gut microbiota are members of two bacterial phyla, Bacteroidetes and Firmicutes (Turnbaugh et al., 2007). Previously, it was thought that human gut microbiomes could be categorized into discrete “enterotypes” with enrichment of Bacteroides, Prevotella, or Ruminococcus forming the basis for three different enterotypes. However, it is now thought that the variability of the gut microbiome across the human population likely forms a continuum as opposed to discrete groups (Jeffery et al., 2012). The person-to-person variability in the gut microbiome is expansive, with individual microbiomes differing by greater than 90% (Parfrey and Knight, 2012).