Fig. 3

Relationships between “trained immunity-mucosal immunity- microbiota”. Upon initial host exposure to the resident microbiota, MAMPs such as β-glucan and LPS interact with PRRs on innate immune cells. This interaction modulates the TCA cycle and glycolysis via the mTOR pathway. The resulting metabolic intermediates directly mediate epigenetic changes through histone modifications, leading to increased accessibility of open-chromatin regions containing inflammatory genes and regulatory elements, thus enhancing cytokine transcription. These epigenetic modifications persist even after immune cells return to baseline, enabling a rapid and efficient response upon re-exposure to similar stimuli. MAMPs, microbial-associated molecular patterns; PRRs, pattern recognition receptors; mTOR, mammalian target of rapamycin; TCA, tricarboxylic acid cycle