Much like the nervous system, enteric microbiota can also modulate intestinal motility. For example, Bifidobacterium bifidum
and Lactobacillus acidophilus
are able to promote motility, while Escherichia
species can inhibit it.6
Metabolic products of intestinal bacteria, such as short-chain fatty acids or chemotactic peptides (for example, N
-formylmethionyl–leucine–phenylalanine) are able to stimulate the enteric nervous system and influence the rate of gut transit.38-40
Disruption of the balance that exists between different enteric microbiota populations might, therefore, predispose the host to altered gut motility and secretion, which results in diarrhea or constipation. These changes are, in turn, likely to influence the balance of enteric microbiota.
Similarly to eukaryotes, prokaryotes communicate with each other through hormones and hormone-like compounds. This pattern of mutual bacterial inter action is called quorum sensing.41
The signaling molecules used for communication by vertebrates, invertebrates and microbes share structural similarities.42,43
Microorganisms can communicate with mamma lian cells via so-called interkingdom signaling, which uses various hormones and hormone-like compounds: peptides and monoamines, such as the epidermal growth factor, and insulin and small, diffusible signaling molecules called autoinducers. Although the signaling molecules that originate from the mammalian host are well-known and characterized, their prokaryotic analogs are not completely understood. N
-acyl homo serine lactones are major autoinducers in Gram-negative bacteria, whereas oligopeptides are involved in inter cellular signaling in Gram-positive bacteria.
Perhaps the best-characterized microbial signaling system is analogous to the eukaryotic, noradrenergic signaling system and involves autoinducer 3—a molecule produced by the microbiota and the bacterial QseC receptor.34,44
Even though neither the molecular structure nor the synthetic pathway of autoinducer 3 are clear,34,45
signaling with this molecule has been intensively studied in pathogenic intestinal bacteria, such as enterohemorrhagic Escherichia coli
O157:H7. Autoinducer 3 binds to the bacterial membrane receptor QseC, which results in its autophosphorylation. QseC then phosphorylates its response regulator, QseB, to initiate a complex signaling cascade that activates the expression of bacterial genes associated with virulence and motility, including the gene that presides over flagellum development.34
Bacteria use quorum sensing to regulate their own gene expression, not only in response to signals from other bacteria, but also in response to host signals. In the enteric microbiota, these signaling mechanisms can mediate diverse physiological functions, including secondary metabolite production, bacterial motility, and pathogenicity.46
The homology of the microbial autoinducer 3–QseC signaling system with the mammalian noradrenergic signaling system, which causes QseC to be activated also by norepinephrine, allows for interkingdom signaling with particular relevance for brain–gut interactions during stress (). Enterohemorrhagic E. coli
can sense luminal norepinephrine or adrenaline to express its virulence traits.45
In pigs, psychological stress has been shown to reactivate subacute salmonella infection.47
Figure 3 Schematic representation of the interkingdom, adrenergic signaling between host and enteric microbiota. NE released into the gut lumen (as spillover from noradrenergic nerve terminals or from capillaries within the gut wall) can activate adrenergic-like (more ...)
That signaling molecules are released by the host into the lumen of the gastrointestinal tract during stress and that receptors and intercellular signaling mechanisms for these same molecules are present on certain luminal microbes34
strongly suggests that the nervous system can also directly modulate microbial behavior. Even though such host to enteric bacteria signaling has only been character ized in detail for pathogenic organisms, and only for some molecules (such as norepinephrine, dynorphins and cytokines),34
similar mechanisms are likely to apply to molecules such as serotonin, somato statin, cholecysto kinin or corticotropin-releasing hormone. These hormones are contained in and secreted from entero chromaffin cells, nerve endings and immune cells.