TY  - EJOU
AU  - Andreescu, Mihaela 
AU  - Tirlea, Laura 
AU  - Tanase, Alina 
AU  - Moldovan, Cosmin Alec 
AU  - Petrut, Stefana 
AU  - Cochior, Daniel 
AU  - Moldovan, Adina-Diana 
AU  - Padurariu-Covit, Monica-Daniela 

TI  - Gut microbiota-driven epigenetic regulation of cytokine gene expression: microbial metabolites, chromatin mechanisms, and clinical perspectives
T2  - European Cytokine Network

PY  - 
VL  - 
IS  - 
SN  - 1952-4005

AB  - Accumulating evidence suggests that the gut microbiota regulates cytokine gene expression through multiple epigenetic mechanisms that shape chromatin states in response to microbial metabolites. Alterations in the gut microbiota have been implicated in the pathogenesis of numerous inflammatory, autoimmune, and metabolic disorders. Key mediators including short-chain fatty acids, bile acids, and tryptophan derivatives modulate histone modifications and DNA methylation at cytokine gene loci, influencing the balance between pro-inflammatory and tolerogenic immune responses. Experimental evidence, including ChIP-seq studies, indicates that microbial colonization promotes regulatory chromatin configurations, while dysbiosis is associated with epigenetic patterns favoring inflammatory cytokine programs. Short-chain fatty acid–mediated histone deacetylase inhibition represents a central mechanism supporting regulatory T cell differentiation and anti-inflammatory cytokine expression. This review summarizes the current evidence linking microbial metabolites, epigenetic regulation, and cytokine expression, while critically discussing the strengths and limitations of the available experimental and translational studies. Although these findings highlight a mechanistic link between the microbiota and cytokine epigenetic regulation, direct evidence in human immune cells remains limited. Further integrative studies are required to support the development of microbiome-informed biomarkers and therapeutic strategies.
KW  - Gut microbiota; immune epigenetics; cytokine regulation; chromatin remodeling; microbial metabolites; short-chain fatty acids; regulatory T cells; NF-κB signaling

DO  - 10.32604/ecn.2026.086087