Epigenome-metabolome-microbiome axis in health and IBD

Abstract

Environmental triggers in the context of genetic susceptibility drive phenotypes of complex immune disorders such as Inflammatory bowel disease (IBD). One such trigger of IBD is perturbations in enteric commensal bacteria, fungi or viruses that shape both immune and neuronal state. The epigenome acts as an interface between microbiota and context-specific gene expression and is thus emerging as a third key contributor to IBD. Here we review evidence that the host epigenome plays a significant role in orchestrating the bidirectional crosstalk between mammals and their commensal microorganisms. We discuss disruption of chromatin regulatory regions and epigenetic enzyme mutants as a causative factor in IBD patients and mouse models of intestinal inflammation and consider the possible translation of this knowledge. Furthermore, we present emerging insights into the intricate connection between the microbiome and epigenetic enzyme activity via host or bacterial metabolites and how these interactions fine-tune the microorganism-host relationship.

Figure 1

Intimate relationship between metabolism and epigenetics. Host cellular and bacteria-derived metabolites as essential co-factors for chromatin modifying enzyme function. Green arrows indicate promotion of enzyme activity, red arrows indicate inhibition of enzyme activity. This figure was created using Biorender.

Figure 2

Epigenetic mechanisms as the intermediary of microorganism-host communication. Schematic of enteric microorganism and metabolic cues that regulate intestinal epithelial cell and immune cell development and function via epigenomic mechanisms. Individual chromatin modifying enzymes demonstrated to be important in this cross-talk are indicated. This figure was created using Biorender.