Published July 2020 | Nature
The “good” bacteria living in our guts do much more than help us digest food and build up our immune systems. Some also play vital roles in helping heal damaged intestinal tissues.
This study, led by co-first authors Shu-en Wu, PhD, and Seika Hashimoto-Hill, DVM, PhD, and corresponding author Theresa Alenghat, VMD, PhD, suggests potential new methods to repair tissue damage among people suffering from inflammatory bowel diseases. Longer term, the study opens doors to a wide range of ways to improve health by controlling the balance of bacteria living inside us.
Specifically, this study details how two opposing forces from bacteria in the gut both act on the epigenetic HDAC3: butyrate, a short chain fatty acid widely sold as a dietary supplement, and inositol phosphate 3 (IP3), a metabolite generated when bacteria break down phytates common in soybeans, nuts and other plant-based foods. In cells lining the intestine, butyrate tends to tamp down HDAC3 activity while IP3 boosts it.
Scientists have detected a number of yin-yang forces at work within our cells, but the twist in this case is that IP3 can come from bacteria, not just our own cells. In mice that had human-like intestinal inflammation, the research team found that IP3 helped damaged tissue heal. When there was not enough IP3, HDAC3 activity and tissue recovery were both impaired.
“This finding is surprising in part because it illustrates how sensitive our health is to constant interactions with organisms that normally live in our bodies. If we can influence these interactions, we may be able to control many diseases that are impacted by our microbiome or diet,” Alenghat says.
How Intestinal HDAC3 Senses Microbiota-Derived Metabolites
Epithelial HDAC3 functions as a central hub for opposing signals generated by microbiota through metabolism of dietary fibers and phytate, which helps modulate enzymatic activity and intestinal epithelial homeostasis/repair.