New research suggests that orally administered lithocholic acid may improve glucose regulation by activating specific bile acid receptors, altering gut bacteria, and reducing liver glucose production in a rat model of type 2 diabetes.
In a rat study, lithocholic acid appeared to improve glucose control by shifting bile acid signalling, altering gut bacteria and dampening the liver’s production of glucose, according to research published by Dove Medical Press. The work adds to a wider body of evidence that excessive hepatic glucose output is a central feature of type 2 diabetes and an important target for treatment. Reviews on diabetes metabolism have long noted that therapies which reduce gluconeogenesis, the liver’s creation of new glucose, may help improve blood sugar control.
The new study focused on lithocholic acid, or LCA, a secondary bile acid that the authors describe as a particularly strong natural activator of TGR5, a bile acid receptor linked to metabolic regulation. Previous research has shown that bile acids can stimulate TGR5 in intestinal L cells and promote the release of glucagon-like peptide-1, better known as GLP-1, a hormone that boosts insulin secretion and helps restrain hepatic glucose production. Work on FXR and TGR5 has also highlighted how closely the two signalling systems interact in the control of glucose and lipid metabolism.
In the current experiment, male Sprague-Dawley rats with streptozotocin-induced diabetes received LCA by mouth for six weeks. Compared with untreated diabetic animals, the LCA group showed lower fasting blood glucose, better glucose tolerance and reduced glycated serum protein, while body weight did not change significantly. The treatment also lowered total cholesterol without materially affecting liver enzymes or most other lipid measures, suggesting a metabolic effect without obvious short-term liver toxicity in this model.
At the molecular level, the researchers reported increased expression of TGR5 and GLP-1 in the terminal ileum, along with higher hepatic TGR5 expression. At the same time, key genes involved in gluconeogenesis, including G6PC, PCK1 and FOXO1, were suppressed. That pattern is consistent with an intestinal signal driving a reduction in the liver’s glucose output, a mechanism that aligns with earlier studies showing that bile-acid signalling through TGR5 can influence incretin release and whole-body glucose homeostasis.
The bile acid data point to a broader shift in intestinal metabolism. LCA treatment increased several secondary bile acids in faeces, including LCA itself, deoxycholic acid, hyocholic acid and tauroursodeoxycholic acid, while primary bile acids changed little. The authors also found that the abundance of certain Clostridia-related microbes rose, whereas Lactobacillus declined. This matters because gut bacteria are known to help convert primary bile acids into secondary forms, and prior studies have linked microbiome-driven bile acid changes to stronger GLP-1 responses and improved metabolic outcomes.
The authors argue that these findings support a model in which oral LCA reshapes the gut environment, encourages bile-acid-transforming bacteria and expands the pool of metabolites that activate TGR5. However, they also caution that the work remains associative rather than definitive. The study did not include receptor-blocking experiments or microbiota transfer, so it cannot prove that the TGR5-GLP-1 pathway caused the glycaemic improvement. Even so, the results fit with a growing literature suggesting that bile acids, the microbiome and enteroendocrine signalling are tightly linked in metabolic disease.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
