Microbial metabolic signaling describes the complex chemical communication system mediated by the bioactive metabolites produced by the gut microbiota that interact directly with host cells and distant organs. These small molecules, including short-chain fatty acids, neurotransmitter precursors, and modified host compounds, act as crucial ligands for host receptors, modulating gene expression, immune function, and endocrine secretion. This signaling pathway is a primary mechanism through which the gut microbiome influences systemic health, mood, and the overall hormonal environment. It represents a fundamental layer of inter-species biological regulation.
Origin
This concept emerged from the recognition that the vast metabolic capacity of the gut microbiome yields thousands of compounds that are absorbed and circulate systemically. It integrates endocrinology, neurobiology, and microbiology, demonstrating that the microbes are not passive residents but active chemical partners. The term emphasizes the direct, informational role of these metabolites in host physiology.
Mechanism
The signaling operates when microbial metabolites bind to specific host receptors, such as free fatty acid receptors (FFARs) on intestinal and immune cells, or when they modulate the activity of host enzymes. For example, microbial modification of tryptophan leads to the production of indoles that activate the aryl hydrocarbon receptor (AhR), influencing intestinal immunity. This constant stream of chemical information directly impacts the hypothalamic-pituitary axis and the metabolism of circulating hormones.
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