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The Microbiota in Immunity and Inflammation

Craig L. Maynard

Humans and other species of mammals are hosts to an array of the mammalian immune system and the microscopic inhabitants
microbial communities collectively referred to as the microbiota. of the various barrier surfaces.
The microbiota comprises prokaryotes (bacteria and archaea),
viruses (bacteriophages as well as eukaryotic viruses), and eukarya Viruses
or the meiofauna (mainly fungi and protozoa). As revealed by The viruses that inhabit mammalian hosts can be subdivided
the Human Microbiome Project, specialized subcommunities into bacteriophages, which infect prokaryotic cells; eukaryotic
colonize barrier surfaces of the digestive, respiratory, and uro- viruses, which infect host and other eukaryotic cells; and virus-
genital tracts, and skin. Our immune system is believed to have derived genetic elements, which can incorporate into host
evolved to ensure peaceful coexistence with these microorganisms chromosomes and result in the generation of infectious virus
that aid in immune homeostasis, pathogen resistance, and diges- at a later date. It has been difficult to quantify the exact size of
tion in exchange for a nutrient-rich habitat. There is a perpetual the virome. In the case of bacteriophages, it is generally accepted
cross-talk between the microbiota and the immune system that they can exist in 10-fold greater numbers than prokaryotes.
throughout an individual’s life. Specific modulation of this Bacteriophages can have profound effects on the structure and
microbiota, particularly in infancy, has important long-term functions of intestinal prokaryotic communities via viral gene
health consequences. Addition of specific symbionts to the transfer of virulence factors and antibiotic-resistant genes between
microbiota can provide tangible health benefits. Reconstitution prokaryotic organisms or through predator–prey relationships.
of a dysbiotic microbiota continues to be utilized or explored Indeed, the infectivity of some enteric viruses requires the
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as therapy for inflammatory diseases. microbiota. Eukaryotic viruses include a vast array of viruses
that permanently infect the host and can exist for decades in
OVERVIEW OF OUR NONMAMMALIAN “SELF” asymptomatic individuals. These viruses can persist locally or
systemically. They can directly impact tissue-specific immunity,
Exposure to the microbiota and its products occurs via a gradual, including in the GI tract.
ordered process. It begins in utero and accelerates during
and after birth. The overall composition of an individual’s Fungi
microbiota is impacted by such phenomena as the method of Collectively referred to as the mycobiota, fungal communities
birth delivery, diet, treatment with antibiotics, and environmental represent a considerably smaller proportion of the total microbes
exposures. All of these modifying factors can have lasting effects in the human body. Commensal fungi can be detected in the
on immune health. mouth, lungs, intestines, vagina, and skin (Fig. 14.2). Advances
in our knowledge and understanding of the size and functions
Prokaryotes of the mycobiota have been hampered by relatively limited
The bacterial component of our microbiota is, by far, the most genomics and bioinformatics capabilities when compared with
widely studied. This has been made possible, in part, by a fairly the study of bacteria or viruses. However, studies utilizing broad-
recent explosion of genomic and bioinformatics capabilities that spectrum antifungal agents have begun to highlight the possible
has enabled taxonomic identification, and even enumeration, roles played by fungi in protecting against disease processes,
of the members of microbial communities without the need for such as inflammatory bowel disease (IBD) (Chapter 75).
bacterial culture. Two phyla—Bacteroidetes and Firmicutes— The microbes that inhabit the human body are often acceptably
account for almost 90% of intestinal bacteria. The remainder referred to as the commensal microbiota, which in the strictest
comprises organisms belonging to the phyla Cyanobacteria, sense refers to organisms that derive benefit from their host
Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicro- without negatively or positively affecting the host. Although this
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bia. The bacteria that colonize humans belong mainly to three is true of some members of the microbiota, our relationship
major phyla: Bacteroidete, Firmicutes, and Proteobacteria. It is with other microbes is one of mutualism, whereby each organism
estimated that the average human being plays host to approxi- performs unique and necessary functions that benefit the other.
mately 100 trillion bacteria. Most of these cells inhabit the lumen For example, certain bacteria find a home in the anaerobic
of the gastrointestinal (GI) tract. The density of bacteria increases environment of the cecum and proximal colon, where they receive
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from ≈10 –10 bacterial cells per mL in the stomach to 10 cells/ a rich source of nutrients in the form of insoluble carbohydrates,
mL in the distal large intestine (Fig. 14.1). The sheer number which our own digestive enzymes are unable to process. By the
of bacteria sets the stage for a very complex relationship between process of anaerobic fermentation, these carbohydrates are broken
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