Bile Acid-Microbiome Interaction Promotes Gastric Carcinogenesis.

Area of Science:

• Gastroenterology
• Oncology
• Microbiology

Background:

• Bile reflux gastritis (BRG) is linked to gastric cancer (GC) development.
• The precise mechanisms involving bile acids and the microbiome remain unclear.

Purpose of the Study:

• To investigate the roles of refluxed bile acids (BAs) and gastric microbiome in gastric carcinogenesis.
• To elucidate the molecular pathways linking BRG to GC.

Main Methods:

• Analysis of gastric juice from BRG and GC patients for BAs, IL-6, LPS, and bacterial composition.
• In vitro cell culture experiments using GES-1 cells.
• In vivo mouse models with bile reflux (BR) surgery or gavage of TDCA, LPS, and Prevotella melaninogenica.
• Treatment with cryptotanshinone, a STAT3 inhibitor.

Main Results:

• Conjugated BAs, IL-6, LPS, and LPS-producing bacteria were elevated in BRG and GC patients.
• Taurodeoxycholic acid (TDCA) positively correlated with LPS-producing bacteria.
• TDCA promoted GES-1 cell proliferation via IL-6/JAK1/STAT3 pathway activation.
• Mouse models confirmed TDCA and LPS effects, and BR-induced lesions were preventable with cryptotanshinone.

Conclusions:

• Refluxed bile acids, particularly TDCA, and LPS-producing bacteria contribute to gastric carcinogenesis through the IL-6/JAK1/STAT3 pathway.
• Targeting the STAT3 pathway with agents like cryptotanshinone may offer a strategy for preventing GC in patients with BRG.