Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis

Abstract

Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids are produced in the liver and are metabolized by enzymes derived from intestinal bacteria, and are critically important for maintenance of a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver–bile acid– microbiota axis and its role in gastrointestinal carcinogenesis in order to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of the recent progress of research in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5). We also highlight the strategies and cutting-edge technologies to target the gut microbiota-dependent alterations in bile acid metabolism in the context of the cancer therapy.

A prospective study of dairy product intake and the risk of hepatocellular carcinoma in U.S. men and women

“…Third, animal studies showed probiotics as well as probiotic fermented dairy products such as yogurt may protect against aflatoxin B1 induced hepatic damage and molecular alterations in hepatic cells during hepatocellular carcinogenesis, and inhibit chemical induced liver tumors . In addition, probiotics show a possible protective effect against hepatocarcinogenesis, through prevention of bile acid toxicity in the intestine and liver . In line with this evidence, we found that yogurt (HR = 0.72) was suggestively inversely associated with HCC risk.…”

Modulation of bile acid profile by gut microbiota in chronic hepatitis B

“…Considering that Bacteroides belongs to the main bacterial genera involved in BA metabolism, we further studied the bacterial taxa that responsible for the key steps of bile acid conversion. Primary bile acids were mostly deconjugated via the action of bile salt hydrolase (BSH).The bacteria Bacteroides, Clostridium, Lactobacillus and Bifidobacterium belongs to the main bacterial genera that express BSH . Bacteria capable of epimerization include Bacteroides, Clostridium and Ruminococcus .…”

“…Gut microbiome convert primary BAs into secondary BAs and therefore possess potent effects on bile acid signalling. In addition, BAs are involved in the regulation of hepatic metabolism and inflammation, and also BAs synthesis via nuclear receptors, such as the farnesoid X receptor (FXR) . Since BAs play an important role in pathophysiology, a better understanding of the relationship between BAs and gut microbiota will shed light on the pathophysiology of fibrosis.…”

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

“…68 Recent pre-clinical studies have also supported a role for microbial alterations in bile acid metabolism, specifically an overabundance of deoxycholic acid (a secondary bile acid), in the development of obesity-related liver cancer. 69 However, it is imperative to highlight that differences in bile acid composition between humans and mice must considered when extrapolating these findings to humans. 70 …”