Regulatory effects of Sini-San on bile acid homeostasis in the enterohepatic circulation of mice with liver fibrosisOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
Researchers tested whether Sini-San (SNS), a classical traditional Chinese medicine formula, protects against liver fibrosis by acting on bile acid metabolism and the gut-liver axis.
How was it studied?
Liver fibrosis was induced in mice with carbon tetrachloride injections or a high-fat, high-sugar diet, then treated orally with SNS. Investigators measured liver injury markers, fibrosis and apoptosis proteins, serum bile acid profiles by LC-MS/MS, bile acid enzyme and transporter expression, and gut microbiota by 16S rRNA sequencing, then repeated key experiments with choline chelation, antibiotic-induced pseudo-sterile conditions, and fxr knockout mice.
What did they find?
Fibrotic mice showed dysregulated bile acid synthesizing enzymes (CYP7A1, CYP27A1), transporters (Bsep, Ntcp, Asbt, Oatp), the FXR receptor, and disrupted gut microbiota. SNS treatment reduced liver injury and fibrosis, corrected bile acid imbalance, normalized these genes, and restored microbial diversity, but its antifibrotic effect was lost after choline chelation, antibiotic treatment, or fxr knockout.
Why it matters
The findings indicate Sini-San's antifibrotic action depends on an intact gut microbiota and FXR signaling, positioning bile acid and gut-liver axis modulation as a multitargeted therapeutic mechanism for liver fibrosis.