Table 3.
Host stress mediators have the capacity to modulate the microbiome
| Stress Mediator | Modes of Action | Location of Synthesis | Regulator(s) | Receptor(s) | Effect on Microbiome |
|---|---|---|---|---|---|
| Cortisol | Stimulates gluconeogenesis, suppresses the immune system, aids with metabolism | Zona fasciculata of the adrenal cortex and epidermal keratinocytes | Production controlled by corticotropin-releasing hormone and ACTH | Glucocorticoid receptor | Alters susceptibility to group A Streptococcus pyogenes skin infections32 |
| Epinephrine | Vasoconstrictor and vasodilator, increases heart rate, bronchodilator, stimulates glycogenolysis, triggers lipolysis | Chromaffin cells of the adrenal medulla and epidermal keratinocytes | Synthesis stimulated by ACTH and the sympathetic nervous system, synthesized primarily from tyrosine | Adrenergic receptors (i.e., α1, α2, β1, β2) | Increases growth of human oral bacteria implicated in periodontal disease7 |
| Norepinephrine | Responsible for vigilant concentration, increases vascular tone, increases heart rate, underlies the “fight-or-flight” response | Chromaffin cells of the adrenal medulla and epidermal keratinocytes | Origin of activation pathway in the brain stem (locus coeruleus), synthesized primarily from tyrosine, must be released from synaptic vesicles to function | Adrenergic receptors (i.e., α1, α2, β1, β2) | Acts as a potent stimulant for bacterial attachment to gut tissues7 |
| Acetylcholine | Major neurotransmitter in the autonomic nervous system, activates skeletal muscle; in the central nervous system, tends to cause antiexcitatory actions | Cholinergic neurons, immune cells, and epidermal keratinocytes | Synthesized by choline acetyltransferase from choline and acetyl-CoA; acetylcholinesterase converts it into inactive metabolites | nAChR and muscarinic acetylcholine receptors | Augments susceptibility to infection by group A Streptococcus and S. aureus18 |
| Catestatin | Vasodilator, functional AMP, exhibits potent catecholamine release-inhibitory activity, stimulates histamine release | Chromaffin cells of the adrenal medulla and epidermal keratinocytes (derived from chromogranin A) | Costored and coreleased with catecholamines from adrenal chromaffin cells and adrenergic neurons | nAChR antagonist; also active in some receptor-independent manners | Exhibits antimicrobial activity against Gram-positive and Gram-negative bacteria in the skin63 |
| Substance P | Functions as a neurotransmitter, neuromodulator of nociception, and AMP; has proinflammatory effects; regulator of anxiety and stress; vasodilator | Secreted by nerves and inflammatory cells | Intense peripheral stimulation, allergens, histamine, prostaglandins, and leukotrienes induce release of substance P | Neurokinin 1 receptor | Indirectly regulates Pseudomonal infections of the cornea64 |
| α-Melanocyte stimulating hormone | Stimulates production of melanin; regulator of appetite, metabolism, and sexual behavior; anti-inflammatory mediator | Intermediate lobe of the pituitary gland, epidermal keratinocyes | Generated from precursor hormone proopiomelanocortin; proteolytic cleavage catalyzed by prohormone convertases | Melanocortin receptors (MC1, MC3, MC4, MC5) | Effective against S. aureus and its biofilms64 |
Several stress factors are synthesized primarily in the adrenal glands and select neurons through a variety of pathways. Each mediator utilizes a specific receptor(s) to trigger a diverse local and systemic response. Together, these responses collectively influence the microbiome in multiple regions of the skin.
ACTH, adrenocorticotropic hormone; nAChRs, nicotinic acetylcholine receptors.