A research team from the A*STAR Genome Institute of Singapore announced on June 15 that gut microbes can influence gene activity in the liver by acting on regulatory DNA elements known as molecular "switches." The findings, published in Molecular Cell, are based on testing over 100,000 human DNA switches linked to liver biology using both in vitro and in vivo approaches. The researchers identified which switches are active under physiological conditions and how microbial signals modify their activity.
The study provides new insights into how gut microbes shape liver function and could lead to advances in precision diagnostics and targeted therapies for liver disease. While previous evidence has linked gut microbial imbalance to liver diseases, the pathway connecting these signals to gene control was not well understood. Genes are influenced not only by their own sequences but also by nearby regulatory elements that determine when and how strongly a gene is expressed.
Researchers conducted a high-throughput evaluation of more than 100,000 human regulatory DNA elements associated with liver biology, sourced from an international research dataset. They found that only a minority of these switches were active in living tissue, mainly those related to metabolism and immune responses—key pathways implicated in liver disease.
A significant portion of the active switches responded to changes in the gut microbiome. When the microbial community shifted, so did the activity of specific DNA switches and their corresponding genes. The team also showed that certain microbe-derived molecules can directly affect switch behavior, supporting evidence that chemical signaling from gut microbes can regulate genes in the liver.
Additionally, researchers identified a rare genetic variation mostly found among East Asian populations that makes at least one regulatory switch more sensitive to microbial inputs. This highlights how genetic differences may affect individual responses to microbiome changes—a key consideration for precision health strategies.
"This work strengthens the scientific base for understanding liver health in the context of the whole body," said Dr. Wan Yue, Executive Director at A*STAR GIS. "By identifying functional regulatory switches in living tissue, it equips the research community with a more reliable framework for discovering targets and developing precision interventions." The team is now collaborating with clinical partners to translate these findings into patient-relevant insights focused on personalised approaches to treating liver disease.
