# The Causal Role of Bile Acids in Cancers of the Digestive System

## TL;DR

Bile acids may play a significant role in causing various cancers of the digestive system by damaging DNA and altering gut microbiomes.

## Contribution

This paper reviews evidence showing bile acids as a likely major cause of digestive system cancers through multiple biological mechanisms.

## Key findings

- Secondary bile acids from high-fat diets damage colonic DNA via oxidative free radicals.
- Bile acids can alter gut microbiomes, leading to inflammation and DNA damage.
- Bile acid reflux contributes to cancers of the esophagus, stomach, and other digestive organs.

## Abstract

Bile acids are widely distributed in the human gastrointestinal tract. A literature review indicates that bile acids may have a role in initiating cancers in every organ of the digestive system. The estimated number of new digestive system cancers world-wide in 2022 was about 5 million. In the particular case of colon cancer, secondary bile acids produced in response to a high fat diet disrupt colonic epithelial cell mitochondrial membranes. This disruption leads to the release of oxidative free radicals that damage DNA, potentially leading to carcinogenic mutations. High levels of colonic bile acids may also alter the gut microbiome, with some bacteria causing inflammation and increased reactive oxygen species leading to DNA damage. Also, bile acids taken up by receptors on the surface of gastrointestinal tract cells can activate NF-kB. In turn, NF-kB may activate a super-enhancer at an oncogene. Bile acid reflux also plays a significant role in esophageal adenocarcinoma, stomach cancer and small intestine carcinogenesis. In addition, cancers of the pancreas, liver, and biliary tract can be caused by the constriction of the common bile duct leading to reflux of bile acids back into these organs. Gastroesophageal reflux involving bile acids may also contribute to hypopharyngeal squamous cell carcinogenesis. Thus, bile acids are a likely major contributory cause of cancer throughout the digestive tract.