The microbiome-epigenome axis: Regulation of host genome function across development and disease

Area of Science:

• Microbiology
• Epigenetics
• Host-Microbe Interactions

Background:

• The gut microbiome is a key regulator of host gene expression, influenced by diet and environmental factors.
• Microbial metabolites act as epigenetic signals, affecting host development, immunity, metabolism, and disease.
• A growing body of evidence points to a complex microbiome-epigenome axis.

Purpose of the Study:

• To synthesize current evidence on the microbiome-epigenome axis.
• To explore how microbial metabolites modulate host epigenetics.
• To highlight the role of this axis in health and disease.

Main Methods:

• Narrative review of existing literature.
• Analysis of studies using germ-free models, recolonization, genetic perturbations, in vitro systems, and human cohorts.
• Integration of data on microbial metabolism, chromatin regulation, and RNA-based control.

Main Results:

• Microbial metabolites like short-chain fatty acids, B vitamins, bile acids, and indoles modulate DNA methylation, histone modifications, and RNA networks.
• Microbial signals significantly impact epigenetic plasticity during development, influencing immune tolerance and metabolic programming.
• Dysbiosis is linked to various diseases, including inflammatory bowel disease, cancer, cardiometabolic disorders, and neurodevelopmental conditions.

Conclusions:

• The gut microbiome acts as a dynamic epigenetic interface between the environment and host physiology.
• Targeted microbiome modulation holds potential for restoring epigenetic homeostasis and enabling precision prevention and therapy.
• Further research is needed to establish causality, resolve mechanisms, and conduct longitudinal multi-omics studies.