Interactive Relationships between Intestinal Flora and Bile Acids

Abstract

The digestive tract is replete with complex and diverse microbial communities that are important for the regulation of multiple pathophysiological processes in humans and animals, particularly those involved in the maintenance of intestinal homeostasis, immunity, inflammation, and tumorigenesis. The diversity of bile acids is a result of the joint efforts of host and intestinal microflora. There is a bidirectional relationship between the microbial community of the intestinal tract and bile acids in that, while the microbial flora tightly modulates the metabolism and synthesis of bile acids, the bile acid pool and composition affect the diversity and the homeostasis of the intestinal flora. Homeostatic imbalances of bile acid and intestinal flora systems may lead to the development of a variety of diseases, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), hepatocellular carcinoma (HCC), type 2 diabetes (T2DM), and polycystic ovary syndrome (PCOS). The interactions between bile acids and intestinal flora may be (in)directly involved in the pathogenesis of these diseases.

Keywords: bile acids; diseases; homeostatic imbalances; interactions; intestinal flora.

Figure 1

Distribution of gastrointestinal bacteria: The distribution of intestinal bacteria in the digestive tract varies, and there are many types and quantities of bacteria in the oral cavity. Following their entry into the esophagus, the colonization of bacteria is reduced. Due to the secretion of gastric acid, most bacteria in the stomach cannot survive, allowing more acid-tolerant bacteria, such as Prevotella, Roche, and Streptococcus, to dominate. The number of bacteria increases from the duodenum to jejunum and ileum. These bacteria include Clostridium, Lactobacillus, and Enterococcus. A large number of bacteria exist in the colon, including Bifidobacterium, Clostridium, Ruminococcus, Bacteroides, Streptococcus, and Prevotella.

Figure 2

Deconjugation pathways of bile acids: Hydrolysis of conjugated bile acids to free bile acids and glycine or taurine by bile salt hydrolase (BSH).

Figure 3

Biotransformation of primary bile acids by Clostridium species: Primary bile acids (CA and CDCA) are biotransformed to the secondary bile acids DCA and LCA, respectively. The processes include multiple steps catalyzed by several enzymes and bile acid transporters encoded by bile acid-inducible (BAI) genes.

Figure 4

Oxidative and isomerization pathways of bile acids: Under the action of the α/β-hydroxy steroid dehydrogenase (HSDH) enzyme of the intestinal bacteria, primary bile acids produce oxygenated bile acid intermediates, which change the stereospecificity of bile acids, reduce their toxicity, and enrich the bile acid types.