Biological function of bile acid and its application prospect in aquaculture

Xu Changfeng 1,2 Wang Haili 2

(1. Xingtai University, Hebei Xingtai 054000;2. Hebei Provincial Key Laboratory of Digital Freshwater Aquaculture Technology, Hebei Xingtai 054000)

Bile acid is an important lipid active component of bile, which is a general term for a variety of alcohols produced by the metabolism of cholesterol in human and animal liver. It is soluble in water, weakly acidic, mainly exists in the hepatointestinal circulatory system, and has a protective effect on the body. Bile acid exists in the form of salt in physiological state and has strong activity, which can effectively reduce the content of triglyceride, accelerate the digestion and absorption of lipids, relieve the digestive pressure caused by high fat eating, and regulate the life activities of the body. In recent years, there are many studies on the function and application of bile acids, such as bile acids also have anti-inflammatory, improve immunity, digestive enzyme activity, and protect intestinal function, which are widely used in aquaculture production. In this paper, the physicochemical properties and mechanism of action of bile acid were described, and the biological function of bile acid and its application in aquaculture were reviewed, which could provide reference for the application of bile acid in aquaculture.

1. Composition and structure of bile acid

Types of 1.1 Bile Acids

According to the source of bile acid, it can be divided into primary bile acid and secondary bile acid. Primary bile acid is a bile acid directly synthesized from cholesterol, and secondary bile acid is produced after 7-α dehydroxylation of primary bile acid. Bile acids can be divided into free bile acids and conjugated bile acids according to their structural properties. The study found that the types and quantities of bile acids contained in different species of bile are not exactly the same. For example, pig bile contains 14 kinds of bile acids; chicken bile acids mainly include chenodeoxycholic acid and cholic acid; cattle and sheep contain the same types of bile acids, but there are differences in various types of bile acids; there are 8 types of rabbit bile acids, of which deoxycholic acid accounts for the largest proportion. The bile acid composition of different kinds of animal bile is shown in Table 1.

Origin and Structure of 1.2 Bile Acids

Bile acid is a derivative produced by cholesterol metabolism, which is mainly generated by cholesterol under the regulation and catalysis of the rate-limiting 7α-hydroxylase, and then the primary bile acid is generated by chemical reactions such as hydroxylation and hydrogenation. Primary bile acids combine with glycine or taurine to form binding bile acids, which undergo a series of reactions such as sulfation and hydroxylation under the action of many active enzymes and flora to produce free bile acids and convert them into secondary bile acids. The bile acid component consists of a five-carbon short fat side chain, a five-carbon sterol ring and three six-carbon sterol rings. The common bile acid structure is shown in Figure 1. Bile acids have hydrophobic and hydrophilic amphiphilic properties, the number and direction of hydroxyl groups determine the hydrophobic surface and surface activity, and the differences in their positions and configurations result in different structures of bile acids.

Figure 1 Common bile acid structure

2. Biological Functions of Bile Acids

2.1 anti-inflammatory

Intestinal bile acid content directly affects the body's inflammatory response. Studies have found that there are significant differences in serum bile acid profiles between healthy individuals and individuals with intestinal inflammation, and appropriate supplementation of bile acid can effectively alleviate inflammation. Bile acids can directly act on intestinal epithelial cells, regulate the secretion of proinflammatory cytokines such as interleukin-8 (IL-8), interleukin-1 (IL-1) and interleukin-6 (IL-6), and can also activate immune cells by binding to receptors FXR and TGR, inhibit the activation of inflammasome NLRP3 and the secretion of proinflammatory cytokines, and alleviate the inflammatory response. Bile acids can also reduce the content of nitric oxide (NO) in the body tissues, strengthen the function of the epithelial barrier, and effectively alleviate the aggravation of inflammation.

2.2 improve immunity

G protein-coupled bile acid receptor (TGR5) is one of the bile acid receptors, which is mainly expressed by macrophages. The combination of bile acid and TGR5 can inhibit the phagocytosis of macrophages and promote its transformation to anti-inflammatory type, so as to improve immunity and protect the health of the body. Bile acid can promote the differentiation of T cells and improve immunity by promoting the expression of specific transcription factors FoxP3 and RORγt; it can also protect the immune organs, reduce the liver load by decomposing endotoxin, enhance liver function, increase the content of immunoglobulin M (IgM), immunoglobulin A (IgA) and complement C4, and enhance the body's non-specific immune response.

2.3 improve digestive enzyme activity

The conversion of primary lipase into lipase has an active role, in which bile acids play an important role. Bile acid can significantly promote the relative expression of SREBF1, FATP4, FAS, ACC mRNA, and regulate the production of key enzymes in the fatty acid synthesis pathway. Bile acid can significantly improve the animal body lipase, lipase, liver lipase activity, combined with lipase to form a complex, change its physical and chemical properties, promote the digestion and absorption of fat.

2.4 guarantee intestinal function

Bile acid receptors GR5, FXR and TGR5 are functional factors that regulate tight junctions, which can directly regulate the expression of connexins, reduce the permeability of the intestinal wall of animals, increase their barrier function, and ensure intestinal health. Bile acids, as endogenous functional small molecules, can enrich epidermal growth factor, stimulate the proliferation of intestinal epithelial cells, and inhibit apoptosis by activating PXR, VDR and TGR5 proteins, which plays an important role in maintaining intestinal health. Bile acid can also regulate mucus secretion, stimulate intestinal epidermal cells to secrete antimicrobial peptides, further strengthen the intestinal protective barrier, and ensure a healthy and stable intestinal flora environment.

2.5 antibacterial

Animal intestinal flora environmental imbalance will lead to the body's digestion and absorption capacity decreased, causing animal diarrhea. Bile acid is a good antibacterial substance and plays an important role in maintaining a healthy intestinal environment. Ubeda and other studies have found that bile acid can significantly promote the secretion of antimicrobial peptides from intestinal epidermal cells, and antimicrobial peptides can significantly promote the number of beneficial intestinal flora, which plays an important role in maintaining intestinal microbial balance, strengthening intestinal chemical protective barrier and ensuring animal health. Bile acids are highly correlated with the expression of farnesoid X-activated receptor gene (FXR), which can affect the composition and quantity of intestinal flora and regulate intestinal barrier function.

3. Application of bile acid in aquaculture

Effects of 3.1 Bile Acids on Growth Performance of Aquatic Animals

Zhu Chuanzhong and other studies showed that the growth of fish fed with 0.2 g/kg bile acid was the best, the average weight gain rate of each fish was 21.05 higher than that of the blank group, and the bait coefficient was the lowest, 1.32. The results showed that compared with the control group, the weight gain rate, specific growth rate and protein efficiency of fish in the bile acid low fat group increased by 12.26, 8.96 and 9.84, respectively; the weight gain rate, specific growth rate and protein efficiency of fish in the bile acid high fat group increased by 8.38, 5.75 and 5.16, respectively; the weight gain rate, specific growth rate and protein efficiency of the high-fat group were increased by 33.41, 26.03 and 26.36 compared with the low-fat group. Therefore, the addition of bile acid can effectively improve the growth performance of aquatic animals and improve the absorption and utilization of fat components in the bait.

Effects of 3.2 Bile Acids on Digestive Enzyme Activities in Aquatic Animals

Bile acids can significantly increase lipase activity in the liver and intestine, and promote the digestion and absorption of high-fat feed in animals. Young larvae of Xiangxiao and other aligned mouth fissure larvae were fed high-fat bait containing 0, 75, 150 and 300 mg/kg bile acid respectively for 70 d. The results showed that with the increase of bile acid addition, protease activity in short intestinal tract gradually increased, lipase activity in pancreas and short intestinal tract increased first and then decreased, of which 150 mg/kg bile acid addition was the best. Chen Qing et al. added 0.5 or 1.0 bile acid salts to the low fish meal bait of young crabs. The results showed that the activities of total protease and lipase in hepatopancreas and intestinal tract of young crabs in each test group were significantly improved, of which 0.5 bile acid was the best. The activities of total protease, hepatopancreas lipase, intestinal protease and intestinal lipase were 21.07, 31.64, 111.69 and 91.36 higher than those in the blank group. Therefore, bile acid can effectively enhance the digestive enzyme activity of aquatic animals and enhance their digestive utilization of high-fat bait.

Effects of 3.3 Bile Acids on Antioxidation in Aquatic Animals

When the body is stimulated by the outside world and produce stress response, excessive ROS will lead to the imbalance of the internal environment of the body, so that cells and the body oxidative damage, and bile acid has a significant antioxidant effect. Xu Kai et al. showed that the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in white shrimp fed bile acid were significantly increased, and the activities of the three activities increased first and then decreased with the addition of bile acid. The activities of SOD, CAT and GSH-Px in 500 mg/kg white shrimp were 11.03, 21.26 and 8.24% higher than those in the blank group. Hu Tianen et al. found that the SOD and GSH-Px activities in bullfrogs gradually increased with the increase of bile acid addition, while the content of malondialdehyde (MDA) decreased significantly when 200 mg/kg bile acid was added, and increased significantly when 300 mg/kg bile acid was added. Therefore, the addition of appropriate amount of bile acid can enhance the antioxidant function of aquatic animals, but excessive amount will be counterproductive and affect the antioxidant function of the body.

Effects of 3.4 Bile Acids on Immune Function of Aquatic Animals

Bile acid can significantly enhance the immunity of aquatic animals and protect the health of the body. Jin et al. found that high-fat 200 mg/kg bile acid diet can significantly increase the activities of lysozyme (LZM) and alkaline phosphatase (AKP) in the liver and serum of juvenile black seabream, while the expression levels of cytokines such as tumor necrosis factor-α(TNF-α) and interleukin-1β (IL-1β) are significantly reduced, and the body immunity is significantly enhanced. Yu and other studies found that the LZM activity, IgM and C4 content of Lateolabrax japonicus fed with taurine were significantly higher than those of the control group. Therefore, bile acids can significantly promote lymphocyte proliferation and antibody secretion, strengthen the function of destroying or eliminating pathogenic microorganisms, and play an important role in immune stress.

4. Conclusions

Bile acid can effectively improve the growth performance, digestive enzyme activity, antioxidant and immune function of aquatic animals, and improve the health of intestinal flora. However, the effect of bile acid on aquatic animals is directly related to its dosage. In the future, when using bile acids in aquaculture, it is necessary to understand the structure, function and effect of bile acid more objectively and comprehensively, and conduct more experiments to explore the best dosage, so as to improve the economic benefits of aquaculture.

References: omitted

Source: Feed Research, 2023,46(04):152-155

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