While our microbiome serves up the metabolites required for our histone modifications, new findings establish that this agglomeration of microorganisms can also serve up a dish most foul; one that induces a severe type of inflammatory bowel disease (IBD) known as Crohn’s disease.
Although studies have established a link between alterations to the microbiome and Crohn’s disease, the lab of Theresa Alenghat at the University of Cincinnati sought to examine H3K4me3, a mark associated with active promoters, to understand how our intestinal cells integrate environmental signals from the microbiome.
Here’s what H3K4me3 ChIP-seq of intestinal epithelial cells isolated from the terminal ilea of eight newly diagnosed pediatric IBD patients of both sexes revealed when compared to eight matched controls:
- Analyses uncovered 1,066 sites of hypermethylation and 539 sites of hypomethylation
- Sites of differential H3K4me3 mainly representpromoters and introns that map to genes involved in immunoregulation, cell survival and signaling, and metabolism, as well as crucial transcription factor motifs
- To manipulate the microbiome, the team examined ileal epithelial cells from conventionally housed and germ-free mice, where they discovered that the microbiome regulates H3K4me3 at a unique subset of Crohn’s disease targets
- While H3K4me3 levels for many of the identified genes correlate with severity of intestinal inflammation in the patients (and RNA-seq of the same patient cells revealed deregulation of critical genes),the majority of differential H3K4me3 sites lack significant differences in gene expression
Overall, this approach highlights the utility of H3K4me3 ChIP-seq in patient samples and animal models to group samples according to diagnosis. However, this approach also exhibits significant advantages over RNA-Seq analysis by revealing many of the key players that control how our intestinal cells integrate signals from the microbiome.
Senior author Theresa Alenghat shares, “This study suggests that the microbiome triggers epigeneticchange that could make some individuals more prone to intestinal inflammation. Each person’s microbiome is drivenby genetics as well as external environmental factors, such as food, where we live, pets, mom’s microbiome, etc.”
Gosee how the microbiome primes an epigenetic profile related to disease over at JCI Insight, September 2018