Emodin inhibits gallstone formation through two complementary mechanisms: modulating gut microbiota to promote proliferation of L. reuteri, and increasing serum TUDCA levels to regulate the HIF1α-AQP8 pathway to alleviate cholestasis.
The medium dose of emodin (30 mg/kg) showed the optimal inhibitory effect on gallstone formation in mice.
Emodin reshaped the intestinal flora structure in gallstone mice and increased the abundance of Limosilactobacillus reuteri (L. reuteri) in vivo.
Emodin elevated serum tauroursodeoxycholic acid (TUDCA) levels in gallstone mice.
Emodin downregulated the expression of hepatic HIF1α and upregulated the expression of AQP8 in gallstone mice.
Correlations were identified between gut microbiota composition, serum metabolites, and liver gene expression in the context of gallstone formation.
Fecal microbiota transplantation (FMT) was used to confirm the functional role of emodin-reshaped gut microbiota in gallstone inhibition.
This research suggests that emodin, a natural compound found in certain plants, can inhibit the formation of gallstones in mice through two connected biological pathways. At a dose of 30 mg/kg, emodin altered the composition of gut bacteria in mice prone to gallstones, particularly increasing the levels of a beneficial bacterium called Limosilactobacillus reuteri. It also raised blood levels of a bile acid compound called TUDCA (tauroursodeoxycholic acid), which then helped regulate two important proteins in the liver — reducing HIF1α and increasing AQP8 — ultimately relieving a condition called cholestasis, where bile does not flow properly. The researchers used a combination of approaches including animal experiments, gut bacteria sequencing, blood metabolite analysis, and computational network pharmacology to map out these mechanisms. They also performed fecal microbiota transplants to confirm that changes in gut bacteria were genuinely responsible for some of the beneficial effects. The study further proposes that the beneficial bacterium L. reuteri may itself contribute to raising TUDCA levels, suggesting the two mechanisms may be interconnected. This research matters because gallstone disease is a very common digestive condition with limited treatment options, and emodin is a naturally occurring compound with a relatively well-established safety profile. These findings suggest that emodin may work through the gut-liver axis — the communication system between intestinal bacteria and liver function — to prevent gallstone formation, potentially opening a new avenue for developing treatments that target both gut microbiota and liver bile regulation simultaneously.
Liu T, Wang H, Lu D, Yan C, Hang F, Ma B, et al.. (2026). Emodin inhibits the formation of gallstones by affecting the intestinal flora and expression of hepatic HIF1α.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.116878