While some of these depend on resident microbial diversity, others depend on
specific taxa.
A diverse microbial community is more likely to occupy all local niches, hindering the recruitment of pathogens just because there is no ecological space left to
occupy. For example, diverse endophyte communities mediate resistance against
pine rust (Ganley et al. 2008), leaf necrosis in cacao trees (Arnold et al. 2003), and
smut in corn (Lee et al. 2009) likely by outcompeting fungal pathogens on plant
tissue and priming the host immune system (Alabouvette et al. 2009; Rodriguez
Estrada et al. 2011; Hartley et al. 2015). The specific mechanisms can be competition
for space, as in endophytes, or for resources, like coliforms in the human gut starving
enterohaemorrhagic E. coli strains by monopolizing organic acids, amino acids, and
other nutrients (Momose et al. 2008a, b; Fabich et al. 2008; Leatham et al. 2009). A
useful approach to test whether multiple species are required to defend a host, is to
compare vulnerability to pathogen infection in hosts inoculated with one or more
symbionts. For example, the resistance of hydra to fungal pathogens is only achieved
when inoculating axenic hydra with a mixture of bacteria from its natural
microbiome, but not with individual bacterial taxa (Fraune et al. 2015).
In other cases, individual taxa that are strong competitors against a pathogen are
sufficient to protect the host (Van der Waaij et al. 1971). These effects have been
found to be strongest with taxa related to the pathogens, likely because they compete
more strongly for the same resources. For example, E.coli produces a bacteriocin
specific to enterohaemorrhagic E coli (Schamberger and Diez-Gonzalez 2002;
Hammami et al. 2013). In the case of defense against Clostridium difficile infections,
the pathogen was found to be inhibited when a bacterium from the same genus,
Clostridium scindens depleted bile acid resources in the gut (Buffie et al. 2015).
Resident microbiota can also protect the host by altering the surrounding environment in a way that disproportionately disadvantages incoming pathogens. For
example, the presence of Lactobacillus crispatus in the female genital tract has been
linked to protective effects against HIV infections, potentially because of reduced
inflammatory responses (Gosmann et al. 2017). Lactobacillus sp. and other normal
microbiota in the vagina maintain a low pH that constrains the invasion of urinary
tract pathogens (Turovskiy et al. 2011; Hickey et al. 2012). Gut microbiota can also
alter their surrounding pH by producing short-chain fatty acids to inhibit intestinal
pathogens (Cherrington et al. 1991; Shin et al. 2002). In many cases, the beneficial
microbes that establish conditions like low pH must arrive earlier than potential
pathogens for the host to be protected (known as “priority effects” in ecology, Toju
et al. 2018).
Microbes can also stimulate the development of the host’s immune system
(Rakoff-Nahoum et al. 2004; Mazmanian et al. 2005). This is of particular interest
in the vertebrate intestine, where commensal bacteria promote epithelial barrier
function, macrophage recruitment, and cytokine precursors (Kamada et al. 2013).
For example, germ-free mice and mice deficient in Nod2 and TLR signaling adaptors
are unable to produce antimicrobial peptides (Kobayashi et al. 2005; Vaishnava et al.
2008). These mice also have reduced intestinal motility and are unable to control
bacterial growth within their mucosa. A healthy microbiome–epithelium relationship
302
C. Cuellar-Gempeler
specific taxa.
A diverse microbial community is more likely to occupy all local niches, hindering the recruitment of pathogens just because there is no ecological space left to
occupy. For example, diverse endophyte communities mediate resistance against
pine rust (Ganley et al. 2008), leaf necrosis in cacao trees (Arnold et al. 2003), and
smut in corn (Lee et al. 2009) likely by outcompeting fungal pathogens on plant
tissue and priming the host immune system (Alabouvette et al. 2009; Rodriguez
Estrada et al. 2011; Hartley et al. 2015). The specific mechanisms can be competition
for space, as in endophytes, or for resources, like coliforms in the human gut starving
enterohaemorrhagic E. coli strains by monopolizing organic acids, amino acids, and
other nutrients (Momose et al. 2008a, b; Fabich et al. 2008; Leatham et al. 2009). A
useful approach to test whether multiple species are required to defend a host, is to
compare vulnerability to pathogen infection in hosts inoculated with one or more
symbionts. For example, the resistance of hydra to fungal pathogens is only achieved
when inoculating axenic hydra with a mixture of bacteria from its natural
microbiome, but not with individual bacterial taxa (Fraune et al. 2015).
In other cases, individual taxa that are strong competitors against a pathogen are
sufficient to protect the host (Van der Waaij et al. 1971). These effects have been
found to be strongest with taxa related to the pathogens, likely because they compete
more strongly for the same resources. For example, E.coli produces a bacteriocin
specific to enterohaemorrhagic E coli (Schamberger and Diez-Gonzalez 2002;
Hammami et al. 2013). In the case of defense against Clostridium difficile infections,
the pathogen was found to be inhibited when a bacterium from the same genus,
Clostridium scindens depleted bile acid resources in the gut (Buffie et al. 2015).
Resident microbiota can also protect the host by altering the surrounding environment in a way that disproportionately disadvantages incoming pathogens. For
example, the presence of Lactobacillus crispatus in the female genital tract has been
linked to protective effects against HIV infections, potentially because of reduced
inflammatory responses (Gosmann et al. 2017). Lactobacillus sp. and other normal
microbiota in the vagina maintain a low pH that constrains the invasion of urinary
tract pathogens (Turovskiy et al. 2011; Hickey et al. 2012). Gut microbiota can also
alter their surrounding pH by producing short-chain fatty acids to inhibit intestinal
pathogens (Cherrington et al. 1991; Shin et al. 2002). In many cases, the beneficial
microbes that establish conditions like low pH must arrive earlier than potential
pathogens for the host to be protected (known as “priority effects” in ecology, Toju
et al. 2018).
Microbes can also stimulate the development of the host’s immune system
(Rakoff-Nahoum et al. 2004; Mazmanian et al. 2005). This is of particular interest
in the vertebrate intestine, where commensal bacteria promote epithelial barrier
function, macrophage recruitment, and cytokine precursors (Kamada et al. 2013).
For example, germ-free mice and mice deficient in Nod2 and TLR signaling adaptors
are unable to produce antimicrobial peptides (Kobayashi et al. 2005; Vaishnava et al.
2008). These mice also have reduced intestinal motility and are unable to control
bacterial growth within their mucosa. A healthy microbiome–epithelium relationship
302
C. Cuellar-Gempeler