Communication of gut microbiota and brain via immune and neuroendocrine signaling

Abstract

The gastrointestinal tract of the human is inhabited by about 5 × 10¹³ bacteria (of about 1,000 species) as well as archaea, fungi, and viruses. Gut microbiota is known to influence the host organism, but the host may also affect the functioning of the microbiota. This bidirectional cooperation occurs in three main inter-organ signaling: immune, neural, and endocrine. Immune communication relies mostly on the cytokines released by the immune cells into circulation. Also, pathogen-associated or damage-associated molecular patterns (PAMPs or DAMPs) may enter circulation and affect the functioning of the internal organs and gut microbiota. Neural communication relies mostly on the direct anatomical connections made by the vagus nerve, or indirect connections via the enteric nervous system. The third pathway, endocrine communication, is the broadest one and includes the hypothalamic-pituitary-adrenal axis. This review focuses on presenting the latest data on the role of the gut microbiota in inter-organ communication with particular emphasis on the role of neurotransmitters (catecholamines, serotonin, gamma-aminobutyric acid), intestinal peptides (cholecystokinin, peptide YY, and glucagon-like peptide 1), and bacterial metabolites (short-chain fatty acids).

Keywords: HPA axis; gut microbiota; gut-brain axis; immune system; vagus nerve.

FIGURE 1

Immune signaling between gut microbiota and central nervous system during eubiosis and dysbiosis. BBB, blood-brain barrier; CNS, central nervous system; DAMPs, damage-associated molecular patterns; IFNγ, interferon gamma; IL-2, interleukin-2; IL-10, interleukin 10; IL-12, interleukin 12; MMP9, matrix metallopeptidase 9; PAMPs, pathogen associated molecular patterns; TGFβ, transforming growth factor β; Th-1, T helper 1 cells; Th-17, T helper 17 cells; TNFα, tumor necrosis factor α; Tregs, regulatory T cells.

FIGURE 2

Influence of injured and inflamed central neurons system on gut microbiota. CNS, central nervous system; DAMPs, damage-associated molecular patterns; IL-10, interleukin 10; TGFβ, transforming growth factor β; Th-1, T helper 1 cells; Th-17, T helper 17 cells; Tregs, regulatory T cells.

FIGURE 3

The role of the vagus nerve in gut microbiota-brain communications. BBB, blood-brain barrier; CCK, cholecystokinin; DA, dopamine; GABA, gamma-aminobutyric acid; GLP-1, glucagon-like peptide-1; 5-HT, serotonin; LPS, lipopolysaccharide; NA, noradrenaline; PYY, peptide YY (PYY); SCFAs, short-chain fatty acids.

FIGURE 4

The role of the hypothalamic-pituitary-adrenal axis in gut microbiota-brain communications. ACTH, adrenocorticotropic hormone; CRF, corticotropin-releasing factor; HPA axis, hypothalamic-pituitary-adrenal axis; IL-1β, interleukin-1 beta; IL-6, interleukin 6; LPS, lipopolysaccharide; SCFAs, short-chain fatty acids; TNFα, tumor necrosis factor α.