How the Gut Microbiome Influences Lean Vs. Obese Phenotypes
Top Breakthrough Discovery | Published August 2018 in Gastroenterology
Theresa Alenghat, VMD, PhD
Similar to the hereditary nature of epigenetics, obese mothers can pass along the bacterial mix in their gut in a way that also makes their children prone to obesity. Now a team of researchers at Cincinnati Children’s reveals a critical mechanism involved—and a potential treatment to control it.
“We wanted to understand what might enable the gut microbiome to affect obesity,” says senior author Theresa Alenghat, VMD, PhD, “and we already knew from our previous research that this particular enzyme, HDAC3, is sensitive to the microbiota.”
In a groundbreaking study, published in Gastroenterology, Alenghat and colleagues reveal that the short-chain fatty acid (SCFA) butyrate plays a critical role in regulating HDAC3 activity in the gut.
The study suggests that decreased butyrate levels in mice fed high-fat diets leads to increased weight gain and susceptibility to obesity-associated sequelae. This systemic effect seems to reflect a loss of intestinal inhibition of the HDAC3 epigenetic-modifying enzyme in intestinal epithelial cells.
“Targeting intestinal HDAC3 directly or through microbiota-based strategies may represent a potential mechanism for specifically preventing obesity and tackling sequelae associated with obesity,” the study states.
The Cincinnati Children’s team included first author Jordan Whitt and co-authors Vivienne Woo, Patrick Lee, Jessica Moncivaiz, Yael Haberman Ziv, MD, PhD, Lee Denson, MD, and Patrick Tso, PhD.