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208 Part One Principles of Immune Response

Microbial load
(per ml)
Glabella
2
Stomach 10 –10 3
Oral cavity
Nare
Oxygen Bile acids Motility AMPs Lactobacilli Duodenum

<10 5 Lung
•Lactobacilli Jejunum
•Streptococci Antecubital
fossa
•Clostridia
•Enterobacteria 3 7 Colon
•Enterococcus Ileum 10 –10
•E. faecalis
•Bacteroides
•Bifidobacteria
•Fusobacteria
•Lactobacilli
•Peptococci Colon and 10 –10 12
9
•Peptostrptococci Cecum
•Prevotellaceae
SCFAs pH •Roseburia Vagina Palm
•Ruminococci
•Verrucomicrobia
FIG 14.1 Spatial Organization of Microbial Communities and
Physiological Gradients Along the Mammalian Gastrointestinal
(GI) Tract. The numbers and types of bacterial communities,
as well as physiological factors, vary along the length of the GI Plantar heel
tract. It is well-appreciated that the oxygen levels, bile acid Toe web
concentrations, intestinal motility, antimicrobial peptides (AMPs), space
and luminal pH in the proximal portion of the GI tract (stomach,
duodenum, jejunum) play major roles in restricting the numbers
and types of microorganisms. In general, aerobic and facultative Aspergillus Cryptococcus Meyerozyma
anaerobic bacteria are found almost exclusively in the proximal Aureobasidium Cystofilobasidium Rhodotorula
portion of the GI tract. The hypoxic nature and more physiological Arthrodermataceae Debaromyces Saccharomyces
pH of the distal small intestine (ileum) and colon, coupled with
overall reductions of bile acids, AMPs, and gut motility, allows Alternaria Epicoccum Others
for unfettered growth of large numbers of obligate anaerobic Candida Fusarium Uncultured
bacteria. These oxygen-sensitive microbes are capable of produc- Cladosporium Malassezia
ing large quantities of short-chain fatty acids (SCFAs; acetate,
propionate, butyrate) from complex carbohydrates (fiber) to be FIG 14.2 The Human Mycobiota. Complex populations of fungi
used for important colonic and immunological processes. (From: have been found associated with the skin and all mucosal surfaces
Reinoso Webb C, Koboziev I, Furr KL, Grisham MB. Protective of the healthy human body. The pie charts indicate the relative
and pro-inflammatory roles of intestinal bacteria [Figure 2]. proportions of fungal genera that are reported to be associated
Pathophysiology 2016;23:67–80.) with the respective sites in representative fungal deep-sequencing
studies. The fungal populations that are found on mucosal
surfaces tend to be more diverse than those on the skin. The
down to generate short-chain fatty acids including butyrate, healthy lung probably reflects mostly environmental fungi, which
which not only is utilized preferentially by colonocytes but also are not included in the key. “Others” refers to sequences that
impacts host immunity and metabolism. Obviously, parasitic represent <1% of the total recovered sequences at each site.
or harmful microbes are not considered part of the commensal “Uncultured” refers to sequences identified in the National Center
microbiota, although organisms that fit this definition can often for Biotechnology Information (NCBI) GenBank database as fungal,
coexist with the microbiota without driving overt disease under but of uncharacterized, origin. Data for pie charts were derived
homeostatic conditions. More recently, the term pathobiont has from studies of the fungal genera that are present in the oral
been coined and is used to refer to any microbe that peacefully cavity, lungs, colon, vagina, and skin. (From: Underhill DM, Iliev
colonizes its host but can evoke severe inflammatory responses ID. The mycobiota: interactions between commensal fungi and
under specific genetic and/or environmental conditions. the host immune system [Figure 1]. Nat Rev Immunol 2014;
14:405–416.)
IMMUNE PREPARATIONS FOR
MICROBIAL COLONIZATION
the first 2–5 years of life in humans. Despite the vast array of
Within the last few years, it has become obvious that the develop- microbes that take up residence in the host, colonization is usually
ing fetus may be exposed in utero to a microbiota or microbial an ordered process that, in most cases, is well tolerated. This is
3
products acquired via the placenta and/or maternal circulation. because of a robust antimicrobial defense system that is initiated
The acquisition of microbial communities continues with the prenatally and fortified postnatally, simultaneous with rapid
passage of the fetus through the birth canal and culminates in microbial colonization.