Summary:
This review describes how diet can act as a long‑term regulator of the immune system by shaping the gut microbiota and influencing epigenetic processes inside immune cells. This is because diet affects the microbes in the gut, and those microbes produce metabolites that can change how genes are switched on or off in immune pathways. These interactions then help set the body’s baseline level of inflammation and influence how reactive the immune system becomes over time. The review highlights that certain nutrients, including fibers, omega‑3 essential fatty acids and polyphenols, encourage microbial communities that produce metabolites such as short‑chain fatty acids and tryptophan‑derived compounds. These metabolites can influence epigenetics and affect immune tolerance. The study also discusses how dietary patterns such as ketogenic diets and intermittent fasting may alter microbiota-epigenome signalling in ways that reshape immune responses. It is discussed that future nutrition strategies should be personalised, taking into account an individual’s microbiome, immune system and epigenetic profile. Overall, this study positions the integration of immunology, microbiome science and epigenetics in clinical research as a positive step forward, and that diet could become a programmable tool for improving immune resilience and treating conditions such as autoimmunity, neuroinflammation, cancer‑related immune dysfunction and chronic inflammatory disease.
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Abstract:
The gut microbiota is emerging as a master regulator of immune homeostasis across infections, cancer, and neuroinflammatory disorders. Dietary inputs dynamically shape microbial ecosystems and induce durable epigenetic reprogramming of host immunity a convergence now defined as nutritional immunoepigenomics. This review posits that specific nutrients (e.g., soluble fibers, omega-3 fatty acids, polyphenols) promote anti-inflammatory microbial profiles that generate metabolites such as short-chain fatty acids and tryptophan catabolites. These act as epigenetic modifiers regulating histone marks (H3K27ac, H3K9me3) and DNA methylation in Tregs, Th17 cells, dendritic cells, and microglia thus modulating immune tolerance and neuroimmune surveillance. I further explore how ketogenic diets and intermittent fasting influence microbiota epigenome signaling. Integrating findings from preclinical and human studies, and highlight translational advances in spectroscopy and multi-omics for non-invasive monitoring of diet-induced immunoepigenetic states. This review advocates precision dietary strategies as programmable modulators of the gut–immune–brain axis to enhance immunological resilience and therapeutic potential.
Article Publication Date: 23/01/2026
DOI: 10.1016/j.clicom.2026.01.004
