Dietary Bile Acids Research Articles

Dietary bile acids supplementation decreases hepatic fat deposition with the involvement of altered gut microbiota and liver bile acids profile in broiler chickens

BackgroundHigh-fat diets (HFD) are known to enhance feed conversion ratio in broiler chickens, yet they can also result in hepatic fat accumulation. Bile acids (BAs) and gut microbiota also play key roles in the formation of fatty liver. In this study, our objective was to elucidate the mechanisms through which BA supplementation reduces hepatic fat deposition in broiler chickens, with a focus on the involvement of gut microbiota and liver BA composition.ResultsNewly hatched broiler chickens were allocated to either a low-fat diet (LFD) or HFD, supplemented with or without BAs, and subsequently assessed their impacts on gut microbiota, hepatic lipid metabolism, and hepatic BA composition. Our findings showed that BA supplementation significantly reduced plasma and liver tissue triglyceride (TG) levels in 42-day-old broiler chickens (P < 0.05), concurrently with a significant decrease in the expression levels of fatty acid synthase (FAS) in liver tissue (P < 0.05). These results suggest that BA supplementation effectively diminishes hepatic fat deposition. Under the LFD, BAs supplementation increased the BA content and ratio of Non 12-OH BAs/12-OH BAs in the liver and increased the Akkermansia abundance in cecum. Under the HFD, BA supplementation decreased the BAs and increased the relative abundances of chenodeoxycholic acid (CDCA) and cholic acid (CA) in hepatic tissue, while the relative abundances of Bacteroides were dramatically reduced and the Bifidobacterium, Escherichia, and Lactobacillus were increased in cecum. Correlation analyses showed a significant positive correlation between the Akkermansia abundance and Non 12-OH BA content under the LFD, and presented a significant negative correlation between the Bacteroides abundance and CA or CDCA content under the HFD.ConclusionsThe results indicate that supplementation of BAs in both LFD and HFD may ameliorate hepatic fat deposition in broiler chickens with the involvement of differentiated microbiota–bile acid profile pathways.Graphical

Effects of Dietary Supplementation of Bile Acids on Growth, Glucose Metabolism, and Intestinal Health of Spotted Seabass (Lateolabrax maculatus).

An 8-week feeding trial was performed to investigate the effects of dietary bile acids on growth, glucose metabolism, and intestinal health in spotted seabass (Lateolabrax maculatus) reared at high temperatures (33 °C). The fish (20.09 ± 1.12 g) were fed diets supplemented with bile acids: 0 (Con), 400 (BA400), 800 (BA800), and 1200 (BA1200) mg/kg, respectively. The results showed that the growth was promoted in fish at the BA800 treatment compared with the control (p < 0.05). Increased enzyme activities and transcripts of gluconeogenesis in the liver were observed, whereas decreased enzyme activities and transcripts of glycolysis, as well as glycogen content, were shown in the BA800 treatment (p < 0.05). The transcripts of bile acid receptors fxr in the liver were up-regulated in the BA800 treatment (p < 0.05). A bile acid supplementation of 800 mg/kg improved the morphological structure in the intestine. Meanwhile, intestinal antioxidant physiology and activities of lipase and trypsin were enhanced in the BA800 treatment. The transcripts of genes and immunofluorescence intensity related to pro-inflammation cytokines (il-1β, il-8, and tnf-α) were inhibited, while those of genes related to anti-inflammation (il-10 and tgf-β) were induced in the BA800 treatment. Furthermore, transcripts of genes related to the NF-κB pathway in the intestine (nfκb, ikkα, ikkβ, and ikbα1) were down-regulated in the BA800 treatment. This study demonstrates that a dietary bile acid supplementation of 800 mg/kg could promote growth, improve glucose metabolism in the liver, and enhance intestinal health by increasing digestive enzyme activity and antioxidant capacity and inhibiting inflammatory response in L. maculatus.

Enhancing growth, liver health, and bile acid metabolism of tilapia (Oreochromis niloticus) through combined cholesterol and bile acid supplementation in plant-based diets

The present study aimed to compare the nutritional effects of cholesterol, bile acids, and combination of cholesterol with bile acids in plant-based diets on juvenile genetically improved farmed tilapia (GIFT; Oreochromis niloticus). The isonitrogenous (321 g/kg crude protein) and isolipidic (76 g/kg crude fat) diets (Con diet) were based on plant protein sources, which included corn gluten meal, soybean meal, cottonseed meal and rapeseed meal. The Con diet was supplemented with 12 g/kg cholesterol (CHO diet), 0.2 g/kg bile acids (BAs diet), a combination of 12 g/kg cholesterol and 0.2 g/kg bile acids (CHO–BAs diet), respectively. Each diet was fed to three tanks in an indoor recirculating aquaculture system for 9 weeks. Results showed that compared to the Con group, fish had a higher weight gain rate, hepatosomatic index, and a lower feed conversion ratio in the CHO–BAs group. The highest levels of whole-fish fat and ash were found in the Con group. Serum parameters, including activities of alanine aminotransferase (ALT) and aspartate transaminase (AST), along with levels of glucose (GLU) and triglyceride (TG) except for total cholesterol (TCHO), were lower in the CHO, BAs, and CHO–BAs groups than those in the Con group (P < 0.001). Histological examination revealed that fish in the Con group exhibited severe hepatocyte vacuolization and diminished hepatocyte proliferation. Gene expression analysis indicated that the transcriptional levels of bile acid metabolism-related genes (including fxr, fgf19, bsep) were up-regulated in the CHO–BAs group (P < 0.05), whereas cholesterol metabolism-related genes (acly and hmgcr) were down-regulated in both CHO and CHO–BAs groups (P < 0.001). Moreover, UPLC-MS/MS analysis revealed that the higher taurine-conjugated bile acids (T-BAs), followed by free bile acids (Free-BAs) and glycine (G-BAs) were determined in tilapia bile. Among these, taurochenodeoxycholic bile acid was the predominant bile acid. Dietary bile acids supplementation also increased the proportion of T-BAs (tauro β-muricholic acid and taurodehydrocholic acid) while decreasing Free-BAs in the fish bile. In conclusion, the incorporation of cholesterol with bile acids into plant-based diets can effectively reduce cholesterol uptake, suppress bile acids synthesis, enhance bile acids efflux, and promote hepatocyte proliferation, which is helpful for maintaining the normal liver morphology in tilapia, and thus improving its growth performance.

Dietary bile acids inclusion improves dietary carbohydrate utilization, antioxidant capacity and intestinal microbiota and inflammation of largemouth bass (Micropterus salmoides)

The study explored the role of dietary bile acids inclusion in improving dietary carbohydrate utilization, antioxidant capacity and intestinal microbiota and inflammation of largemouth bass (Micropterus salmoides). Two isonitrogenous (50.40%) and isolipidic (12.00%) diets were formulated, containing a positive control with 5% α-starch and a negative control with 10% α-starch, respectively. The other three diets were supplemented with 200 mg, 500 mg, or 1000 mg bile acids kg−1 based on 10% α-starch diet. Different experiment diets were fed to cultured fish twice daily for 8 weeks. The results showed that the growth of cultured fish was inhibited by high carbohydrate diet and hepatic glycogen and lipid inordinate accumulation were induced. Meanwhile, high carbohydrate diet caused liver oxidative damage, but supplementation of bile acids significantly improved the antioxidant capacity. Compared with the negative control group, dietary bile acids supplementation didn't affect the growth of largemouth bass, but significantly reduced hepatic glycogen and lipid inordinate accumulation and the viscerosomatic index and hepatosomatic index. In addition, the increase of dietary carbohydrate increased liver bile acids content, and dietary bile acids inclusion could linearly increase liver bile acids content. Results showed that bile acids supplementation regulated liver bile acid synthesis and metabolism of largemouth bass through activating FXR-FGFR4-CYP7A1 pathway. Meanwhile, bile acids inclusion inhibited the expression of foxo1 and genes related to gluconeogenesis, including g6pc, fbp1 and gs, enhanced the expression of genes related to glycolysis, including pfkl and gk through activating insulin pathway. Moreover, high carbohydrate diet with bile acids supplementation also increased gut microbial diversity, and changed the relative abundance of some phyla and genera related to carbohydrate utilization and energy balance, and improved the intestinal inflammatory response. Those findings indicated that dietary bile acids inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota and inflammation of largemouth bass.

Effects of Dietary Bile Acids on Growth Performance, Lipid Deposition, and Intestinal Health of Rice Field Eel (Monopterus albus) Fed with High-Lipid Diets.

The purpose of this trial was to study the positive effects of bile acids (BAs) on growth performance and intestinal health of rice field eel fed with high-lipid diets (HLDs). Rice field eels (initial weight 17.00 ± 0.10 g) were divided into four groups, each group containing four repetitions and feeding with different isonitrogenous diet: control diet containing 7% lipid content, HLDs containing the lipid content increased to 13%, HLDs supplementing with 0.025% BAs and 0.05% BAs, respectively. After 8 weeks, compared control group, the fish fed HLDs had no significant effect on weight gain rate and specific growth rate (P > 0.05), but increased the lipid deposition in tissues and intestinal lipase activity, and damaged to intestinal oxidative stress, inflammatory response, physical barrier, and structural integrity (P < 0.05). Dietary BAs significantly increased weight gain rate and specific growth rate in fish fed with HL diets (P < 0.05) and reduced feed conversation rate (P < 0.05). Further, the eels fed with BAs reduced the total lipid content in liver, muscle, and whole body (P < 0.05). Dietary BAs decreased the activity of intestinal lipase (P < 0.05). Meanwhile, BAs supplemented in HLDs improved intestinal antioxidant capacity through increasing the activities of T-SOD (total superoxide dismutase), GSH-PX (glutathione peroxidase), CAT (catalase), T-AOC (total antioxidant capacity), whereas reducing MDA (malondialdehyde) content (P < 0.05). Moreover, dietary BAs regulated the mRNA expression related to inflammatory response, oxidative stress, and physical barrier in intestine, such as tnf-α, il-8, tlr-8, il-10, nrf2, keap1, claudin12, and claudin15 (P < 0.05). Dietary BAs supplementation also enhanced the intestinal structural integrity characterized by increased fold height and lamina propria width (P < 0.05). This study showed that dietary BAs supplemented in HLDs (13% lipid) could increase the growth performance of rice field eel, reduce lipid deposition in tissues and whole body, and enhance intestinal health.

Bile Acids Promote Hepatic Biotransformation and Excretion of Aflatoxin B1 in Broiler Chickens.

Aflatoxin B1 (AFB1) is a hazardous mycotoxin that often contaminates animal feed and may potentially induce severe liver damage if ingested. The liver is the primary organ responsible for AFB1 detoxification through enzyme-catalyzed xenobiotic metabolism and bile acid (BA)-associated excretion. In this study, we sought to investigate whether exogenous BA improves hepatic AFB1 detoxification to alleviate AFB1-induced liver injury in broiler chickens. Five-day-old broiler chicks were randomly assigned to three groups. CON and AFB1 received a basal diet; AFB1 + BA received a basal diet with 250 mg/kg BA for 20 days. After a 3-day pre-feed, AFB1 and AFB1 + BA were daily gavaged with 250 μg/kg BW AFB1, while CON received gavage solvent for AFB1 treatment. Dietary BA supplementation protected chickens from AFB1-induced hepatic inflammation and oxidative stress. The hepatic biotransformation of AFB1 to its metabolite AFBO was improved, with accelerated excretion to the gallbladder and cecum. Accordantly, AFB1-induced down-regulation of detoxification genes, including cytochrome P450 enzymes, glutathione S-transferases, and the bile salt export pump, was rescued by BA supplementation. Moreover, liver X receptor α, suppressed by AFB1, was enhanced in BA-treated broiler chickens. These results indicate that dietary BA supplementation improves hepatic AFB1 detoxification and excretion through LXRα-involved regulation of xenobiotic enzymes.

Dietary bile acids improve breast muscle growth in chickens through FXR/IGF2 pathway

It is a common practice to provide fast-growing broilers with high-fat diets in the context of integrated farms in Northeast China. Therefore, fat digestion, absorption, and utilization efficiency are critical for broiler meat production. Bile acids (BA) promote fat digestion and absorption, but whether and how BA affects muscle growth in broilers remains unclear. In this study, 1-day-old broilers were fed diets containing varying levels of crude fat (low, medium, and high) with or without BA supplementation for 42 d. Chickens fed a high-fat diet supplemented with BA exhibited significantly (P < 0.05) higher body weight (BW) at 21 d and average daily gain (ADG) during the first 21 d compared to the other groups. Throughout the entire experiment, feed conversion rate (FCR) was significantly (P < 0.05) lower in the high-fat group without the addition of BA, which was further decreased (P < 0.05) with BA supplementation. The improved growth performance in the BA-supplemented high-fat group was associated with significantly (P < 0.05) higher lipase activity in the small intestine chyme, a decreased trend (P = 0.06) in abdominal fat ratio, and significantly (P < 0.05) higher breast muscle mass. Histological analysis revealed significant (P < 0.05) increases in myofiber diameter, cross-sectional area, and RNA and DNA concentrations in the breast muscle of BA-supplemented broilers on the high-fat diet. Additional histological analysis further revealed significant (P < 0.05) enhancements in myofiber diameter, cross-sectional area, and RNA and DNA concentrations within the breast muscles of broilers supplemented with BA and a high-fat diet. The increased insulin-like growth factor 2 (IGF2) in the breast muscle of broilers fed a BA-supplemented high-fat diet correlated with significantly (P < 0.05) increased farnesoid X factor (FXR) protein expression and binding to the IGF2 promoter. These results suggest that dietary BA supplementation improves FCR and breast muscle growth in broilers fed a high-fat diet, potentially through the FXR-mediated IGF2 pathway.

Dietary bile acids supplementation improves the growth performance and alleviates fatty liver in broilers fed a high-fat diet via improving the gut microbiota

This experiment aims to evaluate the effect of bile acids (BAs) in alleviating fatty liver disease induced by a high-fat diet (HFD) in broilers, and the modulation of the gut microbiota involved in this process. A total of 192 one-day-old Arbor Acres (AA) commercial male broilers were randomly divided into 4 groups and treated with the following diet: a basal-fat diet (BFD), a basal-fat diet plus bile acids (BFD + BAs), an HFD, and a high-fat diet plus bile acids (HFD + BAs). Bile acids were supplemented at the early growth stage (3-7 d), middle stage (17-21 d), and late stage (31-35 d). Results showed that BAs treatment had a significant effect on body weight on 14 d and 35 d, and increased the breast muscle weight and its index, but decreased the liver weight and abdominal fat weight on 35 d (P < 0.05). The supplementation of BAs significantly improved the serum lipid profile and decreased the level of triglycerides (TG), total cholesterol (TCHO), and nonesterified fatty acids (NEFA) on 35 d (P < 0.05). Dietary BAs supplementation significantly alleviated the hepatic TG deposition induced by HFD (P < 0.05), which was accompanied by upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and lipoprotein lipase (LPL) gene expression (P < 0.05). Moreover, the expression levels of hepatic gene adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor α (PPARα), and apolipoprotein B (APOB) were greatly increased by BAs treatment. The analysis of 16S rRNA sequencing showed that the microbial diversity of the cecal digesta was increased by BAs in broilers with elevated abundances of Firmicutes, Lactobacillus, Anaerostipes, Sellimonas, and CHKCI002 and decreased abundances of Barnesiella and Akkermansia genus (P < 0.05). Hepatic TG content was positively correlated with the abundance of Oscillospiraceae, but it was negatively correlated with the abundance of Lactobacillus in cecal digesta (P < 0.05). These results indicate that dietary BAs can improve growth performance and alleviate fatty liver disease induced by an HFD via modulating gut microbiota in broilers.

Effects of dietary bile acids levels on growth performance, anti-oxidative capacity, immunity and intestinal microbiota of abalone Haliotis discus hannai

Abalone Haliotis discus hannai (initial weight: 38.79 ± 0.70 g) was used as the experimental animal in a 105-day feeding trial to investigate the influence of dietary bile acids levels on the growth, anti-oxidation, immune response and intestinal microbiota. Six isonitrogenous and isolipidic diets were prepared by adding 0 (control group), 15, 30, 60, 120 and 240 mg/kg of bile acids, respectively (named BA0, BA15, BA30, BA60, BA120 and BA240, respectively). It was found that survival of abalone between groups had no significant difference (P > 0.05). Compared to the control, significant improvements in weight gain rate (WGR) were observed in the groups of BA30 and BA60 (P < 0.05). Based on WGR, the broken line regression model analysis showed that the optimum demand for dietary bile acids for abalone was 35.47 mg/kg. Dietary bile acids increased the total anti-oxidative capacity and activities of catalase, superoxide dismutase, lysozyme and alkaline phosphatase, meanwhile decreased the content of malondialdehyde, alanine aminotransferase and aspartate aminotransferase activities in the cell-free hemolymph (P < 0.05). When bile acids were added to the diets, mRNA levels of genes related to pro-inflammatory factors and apoptosis in the digestive gland were down-regulated (P < 0.05). In contrast, the expression of genes related to anti-oxidation was significantly up-regulated (P < 0.05). The Firmicutes, Actinobacteriota and Proteobacteria were the most abundant phyla in intestine. And dietary bile acids significantly decreased the abundance of Actinobacteria and increased the abundance of Firmicutes (P < 0.05). In conclusion, supplementation of dietary bile acids within 120 mg/kg significantly increased the growth of abalone. The 34.62 mg/kg of dietary bile acids significantly increased the anti-oxidative capacity of abalone. Appropriate levels of dietary bile acids (34.62–61.75 mg/kg) promote the immunity of abalone. Application of appropriate levels of bile acids in diets (34.62 mg/kg) changed the intestinal microbiota and promoted the intestinal health of abalone.

The direct and gut microbiota-mediated effects of dietary bile acids on the improvement of gut barriers in largemouth bass (Micropterus salmoides).

Fish gut barrier damage under intensive culture model is a significant concern for aquaculture industry. This study aimed to investigate the effects of bile acids (BAs) on gut barriers in Micropterus salmoides. A germ-free (GF) zebrafish model was employed to elucidate the effects of the direct stimulation of BAs and the indirect regulations mediated by the gut microbiota on gut barrier functions. Four diets were formulated with BAs supplemented at 0, 150, 300 and 450mg/kg, and these 4 diets were defined as control, BA150, BA300 and BA450, respectively. After 5 weeks of feeding experiment, the survival rate of fish fed with BA300 diet was increased (P<0.05). Histological analysis revealed an improvement of gut structural integrity in the BA150 and BA300 groups. Compared with the control group, the expression of genes related to chemical barrier (mucin, lysozyme and complement 1) and physical barrier (occludin and claudin-4) was increased in the BA150 and BA300 groups (P<0.05), and the expression of genes related to immunological barrier (interleukin [IL]-6, tumor growth factor β, IL-10, macrophage galactose-type lectin and immunoglobulin M [IgM]) was significantly increased in the BA300 group (P<0.05), but the expression of genes related to chemical barrier (hepcidin) and immunological barrier (IL-1β, tumor necrosis factor-α, IL-6 and arginase) was significantly decreased in the BA450 group (P<0.05). Gut microbiota composition analysis revealed that the abundance of Firmicutes was augmented prominently in the BA150 and BA300 groups (P<0.05), while that of Actinobacteriota and Proteobacteria showed a downward trend in the BA150 and BA300 groups (P>0.05). The results of the gut microbiota transferring experiment demonstrated an upregulation of gut barrier-related genes, including immunoglobulin Z/T (IgZ/T), IL-6, IL-1β and IL-10, by the gut microbiota transferred from the BA300 group compared with the control (P<0.05). Feeding the BA300 diet directly to GF zebrafish resulted in enhanced expression of IgM, IgZ/T, lysozyme, occludin-2, IL-6 and IL-10 (P<0.05). In conclusion, BAs can improve the gut barriers of fish through both direct and indirect effects mediated by the gut microbiota.

Immunotoxicity and the mechanisms of aflatoxin B1-induced growth retardation in shrimp and alleviating effects of bile acids

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins prevalent in the environment and food chain, posing severe health risks to humans and animals. Bile acids are natural detergents synthesized from cholesterol and play a key role in the excretion of toxins in vertebrates. Here, pacific white shrimp (Litopenaeus vannamei) served as an animal model to examine the toxicity mechanisms of AFB1 and assess the potential alleviating effects of bile acids against AFB1. Our results revealed that AFB1 exposure significantly inhibited the growth performance and immune response of shrimp, accompanied by AFB1 accumulation and histological damage. Mechanistically, AFB1-induced DNA damage activated DNA repair mechanisms and induced the arrest of cell cycle via the ATR-cyclin B/cdc2 pathway. Additionally, AFB1 directly suppressed the immune response and growth performance of shrimp by inhibiting Toll and IMD pathways and the secretion of digestive enzymes. Notably, dietary bile acids significantly reduced AFB1 accumulation and alleviated AFB1-induced growth retardation and immunotoxicity in shrimp, and CCKAR, ATR, and Relish may be key mediators of the alleviating effects of bile acids. Our study provided new insights into the toxicity mechanisms of AFB1 in invertebrates and highlighted the potential of bile acids to alleviate AFB1 toxicity.

Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota, metabolic activity, and epithelial function

BackgroundIntrauterine growth retardation (IUGR) is one of the major constraints in animal production. Our previous study showed that piglets with IUGR are associated with abnormal bile acid (BA) metabolism. This study explored whether dietary BA supplementation could improve growth performance and colonic development, function, microbiota, and metabolites in the normal birth weight (NBW) and IUGR piglets. A total of 48 weaned piglets (24 IUGR and 24 NBW) were allocated to four groups (12 piglets per group): (i) NBW group, (ii) NBW + BA group, (iii) IUGR group, and (iv) IUGR + BA group. Samples were collected after 28 days of feeding.ResultsThe results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio, while decreased the plasma diamine oxidase (DAO) concentration in the NBW piglets (P < 0.05). Dietary BA supplementation to IUGR piglets decreased (P < 0.05) the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin, suggesting a beneficial effect on epithelial integrity. Moreover, dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance (P < 0.05), whereas Lactobacillus was the dominant genus in the colon. Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA, respectively, which was associated with the colonic function of IUGR piglets. Furthermore, dietary BA supplementation to IUGR piglets upregulated the expressions of CAT, GPX, SOD, Nrf1, IL-2, and IFN-γ in colonic mucosa (P < 0.05).ConclusionsCollectively, dietary BA supplementation could improve the colonic function of IUGR piglets, which was associated with increasing proportions of potentially beneficial bacteria and metabolites. Furthermore, BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.

Dietary bile acids promote sterol metabolism, bile acids enterohepatic circulation, and apoptosis in juvenile Pacific white shrimp (Litopenaeus vannamei)

Bile acids have an important role in the growth and sterol metabolism of shrimp. The aim of this study was to elucidate the effects of bile acids supplementation in the low fishmeal diets on sterol metabolism, bile acids enterohepatic circulation, bile acid profile, and apoptosis in Pacific white shrimp Litopenaeus vannamei. Six diets were formulated in this experiment, HFM diet (25% fishmeal), LFM diet (10 % fishmeal), and LFM supplemented with four levels (0.15, 0.3, 0.6, 0.9 g kg−1) of bile acids, which were LBA1, LBA2, LBA3, LBA4, respectively. Soy protein concentrate and cottonseed protein concentrate blend was used to replace fishmeal of 60 %. After 50 days of feeding trial, the shrimp fed the LBA4 diet showed significantly increased final body weight than that fed the LFM diet (P < 0.05). In the sterol metabolism, the shrimp fed the LBA1 diet was significantly increased the HMG-CoA reductase membrane form (hmgcr) and Niemann-Pick type C-2-like protein (npc2) expression compare with that fed the LFM diet, shrimp in LBA2 group was significantly increased the related genes expression [hmgcr and NPC intracellular cholesterol transporter 1-like (npc1)] than those in the LFM group of hepatopancreas (P < 0.05). In the lipid metabolism, the shrimp in LBA2 group was significantly increased the carnitine palmitoyltransferase-1 (cpt-1) and AMP-activated protein kinase (ampk) expression than that in the LFM group, shrimp in the LBA3 group was significantly increased the fatty acid binding protein fatty acid (fabp) expression than that in the LFM group (P < 0.05). In the bile acids metabolism, the multidrug resistance-associated protein 1-like (mrp2), multidrug resistance-associated protein 2-like (mrp3) and solute carrier family 22 member 7-like (oatp) expressions were significantly increased in LBA1 and LBA2 groups than those in the LFM group of hepatopancreas, organic solute transporter subunit alpha-like (ostα), mrp2, and acyl-coenzyme A thioesterase 1-like (baat) expressions were significantly up-regulated in LBA4 group than those in the LFM group of intestine (P < 0.05). Supplementary bile acids in the diet could decrease the apoptosis-related protein expression (BCL-2 and CASPASE3) compare with the shrimp fed low fishmeal diet (P < 0.05). The concentration of beta MCA in hemolymph bile acids profile increases with bile acids supplementation. The results showed that bile acids enhanced growth performance, promoted sterol metabolism, enhanced enterohepatic circulation, and reduced apoptosis in shrimp on low fishmeal diets. Data availability statementThe data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical.

Bile acid improves growth, lipid utilization and antioxidative status of genetically improved farmed tilapia (Oreochromis niloticus) fed with varying protein-lipid diets reared in inland saline water

A 60-day feeding trial was conducted to find out the effect of bile acid supplemented diets with varying protein and lipid levels on growth performance, body composition, antioxidant status and physio-biochemical responses of genetically improved farmed tilapia (GIFT) juveniles reared in inland saline water (ISW) of 10 ppt. Three hetero-nitrogenous (38–32% crude protein, CP), hetero-lipidic (8–14% lipid) and hetero-caloric (409–439 Kcal digestible energy/100 g) diets were supplemented with three levels (0%, 0.05% and 0.1%) of bile acid to prepare nine experimental diets viz. P38L8B0 (38% CP, 8% lipid and 0% bile acid), P38L8B0.05 (38% CP, 8% lipid and 0.05% bile acid), P38L8B0.1 (38% CP, 8% lipid and 0.1% bile acid), P35L11B0 (35% CP, 11% lipid and 0% bile acid), P35L11B0.05 (35% CP, 11% lipid and 0.05% bile acid), P35L11B0.1 (35% CP, 11% lipid and 0.1% bile acid), P32L14B0 (32% CP, 14% lipid and 0% bile acid), P32L14B0.05 (32% CP, 14% lipid and 0.05% bile acid) and P32L14B0.1 (32% CP, 14% lipid and 0.1% bile acid). Four hundred and five acclimated GIFT juveniles (2.51 ± 0.01 g) were randomly distributed in nine treatment groups in triplicate (stocking density 15 fish/tank, 300 L) following 3 × 3 factorial design. Results indicated that body lipid, feed conversation ratio (FCR), amylase and lipase activities, gill and liver superoxide dismutase (SOD) and catalase (CAT) activities and serum glucose (GLU), total protein, triacylglycerol (TAG), total cholesterol (T-CHO), and low density lipoprotein cholesterol (LDL-CHO) were significantly (p < 0.05) increased and weight gain percentage (WG%), specific growth rate (SGR), protease activity and high density lipoprotein cholesterol (HDL-CHO) were significantly (p < 0.05) decreased with increasing dietary lipid levels and more pronounced effect was found in fish fed 32% protein and 14% lipid. Dietary bile acid significantly (p < 0.05) increased WG%, SGR, protein efficiency ratio, lipase activity and HDL-CHO and significantly (p < 0.05) decreased FCR, gill and liver SOD and CAT activities and serum GLU, TAG, T-CHO, and LDL-CHO with more pronounced effect by 0.05% dietary bile acid. In conclusion, feeding of 35% crude protein, 11% lipid and 0.05% bile acid can cause better growth performance, antioxidant status and physio-biochemical responses of GIFT juveniles reared in ISW of 10 ppt. This information will be useful in formulating the bile acid supplemented eco-friendly low protein high lipid (LPHL) feed for profitable culture of GIFT in ISW.

Dietary Bile Acid Supplementation Could Regulate the Glucose, Lipid Metabolism, and Microbiota of Common Carp (Cyprinus carpio L.) Fed with a High-Lipid Diet.

This study sought to examine the role of bile acids in the regulation of glucose and lipid metabolism, intestinal flora, and growth in high-fat diet-fed common carp (Cyprinus carpio L.). Fish (6.34 ± 0.07 g) were fed for 56 days with three different diets, the control diet (CO, 5.4% lipid), high-fat diet (HF, 11% lipid), and high-fat diet with 60 mg/kg bile acids (BAs, 11% lipid). The results showed that high-fat diets resulted in poor growth performance and increased triglyceride (TG) in serum and the liver. The addition of bile acids significantly alleviated the adverse effects of a high-fat diet. The mRNA expression results indicated that bile acids may improve lipid metabolism through the enhancement of the peroxisome proliferator-activated receptor (PPARa). The expression of gluconeogenesis-related phosphoenolpyruvate carboxykinase (PEPCK) mRNA was inhibited, while fibroblast growth factor 19 (FGF19) was significantly higher. Bile acids reshaped the intestinal microflora community, with the level of Bacteroidetes increasing. The correlation analysis indicated that Patescibacteria, Dependentiae, Myxococcota, and Planctomycetota in the gut are associated with genes involved in glucose and lipid metabolism. These results indicated that bile acids could ameliorate the negative effects of high-fat diets on common carp.

Effect of dietary bile acids supplementation on growth performance, feed utilization, intestinal digestive enzyme activity and fatty acid transporters gene expression in juvenile leopard coral grouper (Plectropomus leopardus)

This study aimed to evaluate the effects of dietary bile acids on growth performance, feed utilization, body composition, digestive enzyme activity, and related gene expression in juvenile leopard coral grouper (Plectropomus leopardus). Five diets with varying levels of dietary bile acids (0, 0.15, 0.3, 0.45 and 0.6%) were formulated and each diet was fed to triplicate groups of 15 fish (13.14 ± 0.14 g) for ten weeks. Results showed that the significant enhancement in weight gain (WG) and specific growth rate (SGR) was observed in fish fed 0.3% bile acids (P &amp;lt; 0.05). Additionally, feed conversion ratio (FCR) was significantly improved with bile acids inclusion (P &amp;lt; 0.05). Higher feed intake was also recorded in bile acids inclusion groups, and significantly up-regulated gene expression of hypothalamus neuropeptide Y (NPY) was found in 0.3% group compared with the control group (P &amp;lt; 0.05). Dietary bile acids (0.3%) significantly decreased lipid deposition in the whole-body (P &amp;lt; 0.05), and lower hepatosomatic index (HSI) and viscerosomatic index (VSI) were also found in this group. Moreover, intestinal trypsin and lipase activities were significantly increased in 0.3% group (P &amp;lt; 0.05) to promote feed digestion. In addition, the relative expression levels of intestinal fatty acid binding protein 2 (FABP2) significantly up-regulated with inclusion of dietary bile acids, suggesting an enhancement of fatty acid transport (P &amp;lt; 0.05). In contrast, cholesterol transport related genes NPC1 like intracellular cholesterol transporter 1 (NPC1L1) and CD36 were notably down-regulated as bile acids inclusion (P &amp;lt; 0.05). This study provides valuable information for the formulation of diets for juvenile coral trout and indicates that dietary bile acids could potentially be used to improve growth performance and feed utilization.

Interaction between dietary lipid and bile acids on the growth performance and lipid metabolism in abalone Haliotis discus hannai Ino

A 105-day feeding trail was conducted to evaluate the effects of dietary lipid and bile acids levels as well as their interactions on the growth, digestion and lipid metabolism in abalone Haliotis discus hannai (initial weight: 5.29 ± 0.02 g). Eight isonitrogenous diets with two levels of lipid (4.3% and 6.3%) and four levels of bile acids (0, 15, 60 and 240 mg/kg) were formulated in a 2 × 4 two-factor design. The results showed that 6.3% of dietary lipid decreased the weight gain rate (WGR) of abalone, which increased as the dietary bile acids level increasing from 0 mg/kg to 60 mg/kg. The treatment with the highest WGR contained 4.3% of dietary lipid and 60 mg/kg of dietary bile acids. In the groups with 4.3% of dietary lipid, the expression of genes involved in lipid transport and lipolysis was increased (P < 0.05). And dietary bile acids increased the expression of genes involved in lipid transport and lipolysis while decreased the expression of genes involved in lipogenesis (P < 0.05). The expression of genes involved in lipid metabolism, such as cluster of differentiation, fatty acid transport protein, microsomal triglyceride transfer protein and peroxisome proliferator-activated receptor α, revealed the interactions between dietary lipid and bile acids (P < 0.05). In conclusion, the growth and digestion of abalone were negatively impacted by an excessively high dietary lipid content (6.3%). Appropriate supplemented level of dietary bile acids (60 mg/kg) significantly enhanced the growth and digestion of abalone. Dietary lipid and bile acids had an interactive effect on the lipid metabolism in abalone, including lipid transport, lipolysis and lipogenesis.

Effect of dietary bile acids: Growth performance, immune response, genes expression of fatty acid metabolism, intestinal, and liver morphology of striped catfish (Pangasianodon hypophthalmus)

Seven isonitrogenous (31.70% protein) and isolipidic (5.20%) experimental diets were made by supplementing a control diet (BA0) with 0.25, 0.50, 0.75, 1.0, 1.25, and 1.5 g bile acid (BA) kg−1 diet, respectively. The diets were fed to striped catfish (Pangasianodon hypophthalmus) to monitor the effects on the growth, non-specific immune response, gene expression of fatty acids metabolism, liver, and their intestinal morphology. The average initial fish weight was 10.3 ± 0.20 (SD) g. The diets were randomly assigned to 21 hapas, each stocked with 10 fish and fed for 70 days. Supplementing BA1.0 and BA1.25 significantly improved growth and nutrient utilization (P < 0.05) compared to BA0 and other treatments. Additionally, the hematological analyses red blood cell count (RBC), haemoglobin, packed cell volume (PCV) and white blood cell count (WBC) amplified in the subsequent order: BA1.0, BA1.25, BA0.75, BA1.50, and BA0.50 g kg−1 diet and finally BA0.25 g kg−1 diet compared to the control diet. The rates of serum lysozyme activity, biochemical parameters, phagocytic index, phagocytic activity, and antioxidants parameters were considerably improved (P ≤ 0.05) in fish fed diets BA1.0 and BA1.25. In the intestinal measurement and liver histomorphometricall, the highest values were observed on BA1.0 and BA1.25. Among the five genes assayed in the liver tissues, peritoneal fat, and musculature levels of ATGL, HSL, and CPT-1, genes expression increased in fish fed diets with increasing levels of bile acid added to the diet while, the expression of PPARα and FAS decreased. Consequently, bile acids are recommended at levels of 1.0–1.25 g kg−1 diet to improve the growth performance and immune status of striped catfish.

Bile acids as carcinogens in the colon and at other sites in the gastrointestinal system.

Colon cancer incidence is associated with a high-fat diet. Such a diet is linked to elevated levels of bile acids in the gastrointestinal system and the circulation. Secondary bile acids are produced by microorganisms present at high concentrations in the colon. Recent prospective studies and a retrospective study in humans associate high circulating blood levels of secondary bile acids with increased risk of colon cancer. Feeding mice a diet containing a secondary bile acid, so their feces have the bile acid at a level comparable to that in the feces of humans on a high-fat diet, also causes colon cancer in the mice. Studies using human cells grown in culture illuminate some mechanisms by which bile acids cause cancer. In human cells, bile acids cause oxidative stress leading to oxidative DNA damage. Increased DNA damage increases the occurrence of mutations and epimutations, some of which provide a cellular growth advantage such as apoptosis resistance. Cells with such mutations/epimutations increase by natural selection. Apoptosis, or programmed cell death, is a beneficial process that eliminates cells with unrepaired DNA damage, whereas apoptosis-resistant cells are able to survive DNA damage using inaccurate repair processes. This results in apoptosis-resistant cells having more frequent mutations/epimutations, some of which are carcinogenic. The experiments on cultured human cells have provided a basis for understanding at the molecular level the human studies that recently reported an association of bile acids with colon cancer, and the mouse studies showing directly that bile acids cause colon cancer. Similar, but more limited, findings of an association of dietary bile acids with other cancers of the gastrointestinal system suggest that understanding the role of bile acids in colon carcinogenesis may contribute to understanding carcinogenesis in other organs.

Dietary bile acid supplementation alters plasma biochemical and hormone indicators, intestinal digestive capacity, and microbiota of piglets with normal birth weight and intrauterine growth retardation.

Piglets with intrauterine growth retardation (IUGR) have poor small intestinal morphology and function, resulting in impaired digestion and absorption of nutrients and lower growth performance. Bile acids (BA) are important in regulating digestive enzyme activity, digestion and absorption of lipids, intestinal development, and protecting the liver. The present study aimed to investigate the effects of dietary BA supplementation on plasma biochemical and hormone indicators, intestinal morphology and function, and microbial community in piglets with normal birth weight (NBW) and IUGR. Weaned piglets (24 IUGR and 24 NBW) were allocated to four groups (12 piglets per group) and fed the following diets: (i) NBW group, NBW piglets fed a basal diet; (ii) NBW + BA group, NBW piglets fed a basal diet with 400 mg/kg BA; (iii) IUGR group, IUGR piglets fed a basal diet; and (iv) IUGR + BA group, IUGR piglets fed a basal diet with 400 mg/kg BA. The feeding trial lasted 28 days. The results showed that IUGR decreased the weight of the jejunum, whereas dietary BA supplementation decreased the jejunum weight and increased the length, weight, and index of ileum in NBW piglets (p < 0.05). In addition, IUGR increased (p < 0.05) the plasma choline esterase (CHE) and glucose levels of weaned piglets regardless of BA supplementation. Dietary BA supplementation increased the plasma albumin, triglyceride, and total protein concentrations while decreased plasma aspartate transaminase (AST), alanine aminotransferase (ALT), CHE, lactate dehydrogenase, and NH3 levels regardless of IUGR (p < 0.05). The IUGR increased trypsin level in the ileum, whereas dietary BA supplementation decreased jejunal trypsin and lipase and ileal lipase levels of weaned piglets regardless of IUGR (p < 0.05). Spearman's correlation analysis revealed the potential link between the intestinal microbial community and intestinal health-related indices of weaned piglets. These findings suggest that IUGR could decrease small intestinal morphology and function, whereas dietary BA supplementation could promote the ileum development of NBW piglets, protect the liver by reducing plasma ALT and AST levels, and increase the proportion of potentially beneficial bacteria in the small intestine of NBW and IUGR piglets, contributing to intestinal development and health of weaned piglets.