Total Bile Acid Concentration Research Articles

Quality Assessment by Bile Composition in Normothermic Machine Perfusion of Rat Livers.

Background: The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) is used for improved preservation. Due to the mimicked invivo conditions during normothermic machine perfusion, the liver is metabolically active, which allows quality assessment during perfusion. Bile seems to be of rising interest in clinical studies, as it is easily collectible for analysis. As there are currently no data on biliary bile acids during NMP, the primary objective of this study was to use our experimental rodent NMP model to assess changes in bile composition through organ damage during perfusion to inform clinical evaluation of donor organs during NMP. Methods: Thirty livers from male Sprague-Dawley rats in five groups underwent 6 h of NMP using either erythrocyte-supplemented DMEM or Steen solution, with or without 30 min of warm ischemia time (WIT). We conducted regular measurements of AST, ALT, LDH, and urea levels in the perfusate at 3-hour intervals. Bile samples were analyzed for biliary pH, LDH, and gamma glutamyltransferase, as well as biliary bile acids via mass spectrometry and UHPLC. Results: Compared with regular livers, liver injury parameters were significantly higher in our donation after circulatory death (DCD) model. Bile production was significantly reduced in livers exposed to WIT, and the bile showed a significantly more alkaline pH. This correlated with the concentration of total bile acids, which was significantly higher in livers experiencing WIT. However, regular livers produced a higher total amount of biliary bile acids during perfusion. Taurocholic acid and its metabolites were most prominent. Secondary bile acids were significantly reduced during perfusion due to the missing enterohepatic circulation. Conclusions: WIT-induced liver injury affects bile composition within our small-animal NMP model. We hypothesize this phenomenon to be attributed to the energy-driven nature of bile secretion, potentially explaining why DCD livers produce less, yet more concentrated, bile. Our results may inform clinical studies, in which biliary bile acids might have a potential as a quantifiable viability marker in human NMP liver transplantation studies.

Neoagarotetraose Alleviates Atherosclerosis via Modulating Cholesterol and Bile Acid Metabolism in ApoE-/- Mice.

Atherosclerosis is closely associated with metabolic disorders such as cholesterol accumulation, bile acid metabolism, and gut dysbiosis. Neoagarotetraose supplementation has been shown to inhibit obesity and alleviate type 2 diabetes, but its effects on modulating the development of atherosclerosis remain unexplored. Therefore, the present study was conducted to investigate the protective effects and potential mechanisms of neoagarotetraose on high-fat, high-cholesterol diet (HFHCD)-induced atherosclerosis in ApoE-/- mice. The results showed that neoagarotetraose supplementation decreased the atherosclerotic lesion area by 50.1% and the aortic arch lesion size by 80.4% compared to the HFHCD group. Furthermore, neoagarotetraose supplementation led to a significant reduction in hepatic lipid content, particularly non-high-density lipoprotein cholesterol. It also resulted in a substantial increase in total bile acid content in both urine and fecal samples by 3.0-fold and 38.7%, respectively. Moreover, neoagarotetraose supplementation effectively downregulated the intestinal farnesoid X receptor by 35.8% and modulated the expressions of its associated genes in both the liver and intestine. In addition, correlation analysis revealed strong associations between gut microbiota composition and fecal bile acid levels. These findings highlight the role of gut microbiota in neoagarotetraose-mitigating atherosclerosis in HFHCD-fed ApoE-/- mice. This study indicates the potential of neoagarotetraose as a functional dietary supplement for the prevention of atherosclerosis.

Enteral Agonism of the Farnesoid X Receptor-Fibroblast Growth Factor 19 Axis Prevents Cholestasis in TPN-Fed Piglets

Total parenteral nutrition (TPN) administration provides necessary nutrients to infants who cannot tolerate enteral feedings. However, the use of TPN can result in cholestasis which can cause parenteral nutrition-associated liver diseases. Previous mitigation strategies for cholestasis have included administering bile acids enterally to encourage normal bile acid metabolism. The objective of this study was to determine if treatment of either ursodeoxycholic acid (UDCA), Tropifexor (TPX), or fibroblast growth factor 19 (FGF19) will prevent cholestasis in a piglet TPN model through the activation of the farnesoid X receptor (FXR)-FGF19 axis. We hypothesize that UDCA will have minimum effects on FXR while TPX, a potent FXR agonist, will significantly affect the FXR pathway, and FGF19 will reduce bile acid synthesis to alleviate cholestasis. Piglets received TPN for 3 weeks and were treated enterally with either UDCA (25 mg/kg*day) or TPX (7.5 μg/kg*day) with minimal milk-based formula (12 mL/kg*day), or daily intravenous FGF19 (0.25 mg/d) injection. Body weight gain was not different after 3 weeks. Plasma markers of cholestasis such as of total bile acids, bilirubin, and gamma-glutamyl transferase were lower in pigs that received TPX compared to the control treatment at the end of the study. Circulating levels of FGF19 and tissue concentrations of total bile acids were not different across treatments. In the ileum, TPX increased mRNA expression of FGF19, ileal lipid binding protein, and organic solute transporter α compared to the control pigs. All treatments reduced the mRNA expression of apical sodium-dependent bile acid transporter compared to the control treatment. TPX also increased mRNA expression of small heterodimer protein and bile salt export pump in the liver. Overall, we conclude that UDCA and FGF19 had minimal effects on cholestasis, whereas TPX prevented cholestasis in part via activation of the FXR-FGF19 axis in TPN fed piglets. NIDDK R01-DK094616 K01 DK129408 T32 NIH grant DK07664. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Expression of hepatic genes involved in bile acid metabolism in dairy cows with fatty liver

Bile acids are cholesterol-derived molecules that are primarily produced in the liver. In nonruminants with fatty liver, overproduction of bile acids is associated with liver injury. During the transition period, fatty liver is a metabolic disorder that can affect up to 50% of high-producing dairy cows. The purpose of this study was to provide a comprehensive evaluation on hepatic bile acid metabolism in dairy cows with fatty liver by assessing expression changes of genes involved in bile acid synthesis, export and uptake. The serum activities of aspartate aminotransferase, alanine aminotransferase and glutamate dehydrogenase and concentration of total bile acids were all greater, whereas serum concentration of total cholesterol was lower in cows with fatty liver than in healthy cows. Content of total bile acids was higher but total cholesterol was slightly lower in liver tissues from fatty liver cows than from healthy cows. The hepatic mRNA abundance of cholesterol 7a-hydroxylase (CYP7A1), hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 7 (HSD3B7) and sterol 12α-hydroxylase (CYP8B1), enzymes involved in the classic pathway of bile acid synthesis, was higher in fatty liver cows than in healthy cows. Compared with healthy cows, the hepatic mRNA abundance of alternative bile acid synthesis pathway-related genes sterol 27-hydroxylase (CYP27A1) and oxysterol 7α-hydroxylase (CYP7B1) did not differ in cows with fatty liver. The protein and mRNA abundance of bile acid transporter bile salt efflux pump (BSEP) were lower in the liver of dairy cow with fatty liver. Compared with healthy cows, the hepatic mRNA abundance of bile acid transporters solute carrier family 51 subunit α (SLC51A), ATP binding cassette subfamily C member 1 (ABCC1) and 3 (ABCC3) was greater in cows with fatty liver, whereas the solute carrier family 51 subunit β (SLC51B) did not differ. The expression of genes involved in bile acid uptake, including solute carrier family 10 member 1 (NTCP), solute carrier organic anion transporter family member 1A2 (SLCO1A2) and 2B1 (SLCO2B1) was upregulated in dairy cows with fatty liver. Furthermore, the hepatic protein and mRNA abundance of bile acid metabolism regulators farnesoid X receptor (FXR) and small heterodimer partner (SHP) were lower in cows with fatty liver than in healthy cows. Overall, these data suggest that inhibition of FXR signaling pathway may lead to the increased bile acid synthesis and uptake and decreased secretion of bile acids from hepatocytes to the bile, which elevates hepatic bile acids content in dairy cows with fatty liver. As the hepatotoxicity of bile acids has been demonstrated on nonruminant hepatocytes, it is likely that the liver injury is induced by increased hepatic bile acids content in dairy cows with fatty liver.

Polysaccharides of Aspergillus cristatus attenuate obesity by regulating gut microbiota and gut microbiota-related metabolites

Golden-flower fungus, the only dominant microorganism determining the Fu-brick tea quality through fermentation and the important microbe in Liupao tea, is considered a potential probiotic fungus based on its anti-obesity effect. However, the classification of golden-flower fungi is still controversial; the anti-obesity effect of golden-flower fungus polysaccharides remains unknown. In this study, we identify a golden-flower strain as Aspergillus cristatus based on morphological characteristics and multigene phylogeny analysis, which resolves the controversy of classification. Moreover, we find A. cristatus polysaccharides (ACPS) attenuate obesity in rats. ACPS modulate gut bacterial composition, in which Akkermansia, Akkermansia muciniphila, Bacteroides, Romboutsia, Blautia, and Desulfovibrio are considered the core microbes regulated by ACPS. ACPS increase fecal total short-chain fatty acid content and serum, hepatic, and fecal total bile acid content. Furthermore, ACPS-induced gut microbiota alteration plays a causal role in the protection from obesity, according to a fecal transplantation experiment. Thus, ACPS ameliorate obesity by regulating gut microbiota and gut microbiota-related metabolites.

Effect of lotus seed resistant starch on the bioconversion pathway of taurocholic acid by regulating the intestinal microbiota

Taurocholic acid (TCA) is abundant in the rat intestine and has multiple health benefits. In the gut, intestinal microbiota can transform TCA into different bile acid (BA) derivatives, with the composition of microbiota playing a crucial role in the transformation process. This study aims to investigate how lotus seed resistant starch (LRS) can regulate microbiota to influence BA transformation. A fecal fermentation study was conducted in vitro, using either LRS, high-amylose maize starch (HAMS), or glucose (GLU) to analyze microbiota composition, BA content, and metabolic enzyme activities over different fermentation times. Bioinformatics analysis found that LRS increased the relative abundance of Enterococcus, Bacillus, and Lactobacillus, and decreased Escherichia-Shigella, compared with HAMS and GLU. LRS also reduced total BA content and accelerated the conversion of TCA to cholic acid, deoxycholic acid, and other derivatives. These results reveal that LRS and GLU tend to mediate the dehydroxy pathway, whereas HAMS tends to secrete metabolic enzymes in the epimerization pathway. Therefore, the evidence that LRS may regulate TCA bioconversion may benefit human colon health research and provide an important theoretical basis, as well as offer new concepts for the development of functional foods.

Gestational diabetes mellitus aggravates adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy

PurposeTo evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP.MethodsThis multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records. Univariate and multivariate logistic regression analysis were used to compare the incidence of perinatal outcomes between ICP with GDM group and ICP alone group.ResultsBaseline characteristics of the population revealed that maternal age (p < 0.001), pregestational weight (p = 0.01), pre-pregnancy BMI (p < 0.001), gestational weight gain (p < 0.001), assisted reproductive technology (ART) (p < 0.001), and total bile acid concentration (p = 0.024) may be risk factors for ICP with GDM. Furthermore, ICP with GDM demonstrated a higher association with both polyhydramnios (OR 2.66) and preterm labor (OR 1.67) compared to ICP alone. Further subgroup analysis based on the severity of ICP showed that elevated total bile acid concentrations were closely associated with an increased risk of preterm labour, meconium-stained amniotic fluid, and low birth weight in both ICP alone and ICP with GDM groups. ICP with GDM further worsened these outcomes, especially in women with severe ICP. The nomogram prediction model effectively predicted the occurrence of preterm labour in the ICP population.ConclusionsICP with GDM may result in more adverse pregnancy outcomes, which are associated with bile acid concentrations.

Cholesterol-Lowering and Antioxidant Effects of Pork-Liver Protein Hydrolysate in Otsuka Long-Evans Tokushima Fatty Rats.

In this study, we investigated the effects of a porcine liver protein hydrolysate (PLH) diet on lipid metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type II diabetes. OLETF rats (20-wk-old males) were pair-fed with either a PLH diet containing 20% PLH or a casein diet for 14 wk. Dietary PLH significantly lowered serum cholesterol and phospholipid concentrations, mainly by decreasing low-density lipoprotein and high-density lipoprotein fractions. Fecal cholesterol was significantly increased in the PLH diet group; however, the total bile acid concentration in the feces was not significantly different between the groups. In addition, the PLH diet significantly decreased serum thiobarbituric acid reactive substance concentrations. These results suggest that dietary PLH exerts hyperlipidemic and antioxidant effects, indicating that it is a novel functional food ingredient.

The alteration of mucosal bile acid profile is associated with nerve growth factor expression in mast cells and bowel symptoms in diarrhea-predominant irritable bowel syndrome.

Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (n = 7, 19.4%) and BA-L (n = 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms.

Enhancing milk quality and modulating rectal microbiota of dairy goats in starch-rich diet: the role of bile acid supplementation.

Diets rich in starch have been shown to increase a risk of reducing milk fat content in dairy goats. While bile acids (BAs) have been used as a lipid emulsifier in monogastric and aquatic animals, their effect on ruminants is not well understood. This study aimed to investigate the impact of BAs supplementation on various aspects of dairy goat physiology, including milk composition, rumen fermentation, gut microbiota, and BA metabolism. We randomly divided eighteen healthy primiparity lactating dairy goats (days in milk = 100 ± 6 d) into two groups and supplemented them with 0 or 4g/d of BAs undergoing 5weeks of feeding on a starch-rich diet. The results showed that BAs supplementation positively influenced milk yield and improved the quality of fatty acids in goat milk. BAs supplementation led to a reduction in saturated fatty acids (C16:0) and an increase in monounsaturated fatty acids (cis-9 C18:1), resulting in a healthier milk fatty acid profile. We observed a significant increase in plasma total bile acid concentration while the proportion of rumen short-chain fatty acids was not affected. Furthermore, BAs supplementation induced significant changes in the composition of the gut microbiota, favoring the enrichment of specific bacterial groups and altering the balance of microbial populations. Correlation analysis revealed associations between specific bacterial groups (Bacillus and ChristensenellaceaeR-7group) and BA types, suggesting a role for the gut microbiota in BA metabolism. Functional prediction analysis revealed notable changes in pathways associated with lipid metabolism, suggesting that BAs supplementation has the potential to modulate lipid-related processes. These findings highlight the potential benefits of BAs supplementation in enhancing milk production, improving milk quality, and influencing metabolic pathways in dairy goats. Further research is warranted to elucidate the underlying mechanisms and explore the broader implications of these findings.

Predictive value of serum TBA for 2-year MACEs in ACS patients undergoing PCI: a prospective cohort study

Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan–Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (β: 1.7, 95% confidence interval [CI] 0.3–3.0), particularly in the male (β: 2.0, 95% CI 0.3–3.6) and 50–69-year-old (β: 2.5, 95% CI 0.6–4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595–0.703) and 0.783 (95% CI 0.685–0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

Gender-Specific Bile Acid Profiles in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. A main cause is the obesogenic, so-called Western lifestyle. NAFLD follows a long, unperceived course, and ends potentially fatally. Early diagnosis of aggressive subtypes saves lives. So far, non-invasive means of detection are limited. A better understanding of the pathogenic interplay among insulin resistance, immune inflammation, microbiome, and genetic background is important. Metabolomics may give insight into these interlaced processes. In this study, we measured bile acids (BA) in the plasma of adult NAFLD and alcohol-associated liver disease (ALD) patients and healthy controls with targeted mass spectrometry. We focused on gender-related bile acid production pathology in NAFLD and ALD. Compared to healthy controls, women with NAFLD had significantly higher concentrations of total BA, total primary BA, total cholic (CA), total chenodeoxycholic (CDCA), total glycine-conjugated, and total non-12-a-OH BA. Concerning subtypes, glycocholic (GCA) and glycochenodeoxycholic (GCDCA), BA were elevated in women with NAFLD. In contrast, men with NAFLD had no significantly altered total BA fractions. However, the subtypes GCA, glycodeoxycholic (GDCA), glycolithocholic (GLCA), lithocholic (LCA), taurolithocholic (TLCA), and tauroursodeoxycholic acid (TUDCA) were elevated, while CA was significantly decreased. In NAFLD, except ursodeoxycholic acid (UDC), all total BA correlated significantly positively in both sexes with the ELF score, while in ALD, only males showed significant correlations exceptive for total UDC BA. In NAFLD, total BA, total primary BA, total secondary BA, total free secondary BA, total CA, total CDCA, total taurine conjugated, total glycine conjugated, total 12-a-OH, and total non-12-a-OH were significantly higher in cases of a high enhanced liver fibrosis (ELF) score above 9.8. In ALD, total UDC was additionally elevated. Between NAFLD with and without NASH, we found no significant differences. Our data show gender-specific bile acid profiles in NAFLD and markedly different BA patterns in ALD. Women with NAFLD had more severe cholestasis. Men may better compensate fat storage-driven bile acid dynamics, indicated by higher levels of taurine-conjugated BA, which associate with beneficial metabolic functions.

Effects of replacing fishmeal with different proportions of mixed protein source in the diet of largemouth bass (Micropterus salmoides)

Fishmeal is an important protein source for largemouth bass (Micropterus salmoides). However, the production of fishmeal is decreasing each year and the price of fishmeal is rising. Therefore, it is necessary to find new high-quality and suitable protein sources. This study used a mixed animal protein source (chicken meal:blood meal:shrimp meal:brewer's yeast = 50:12.5:25:12.5) to replace fishmeal. Using a 48 % fishmeal group as the control, five diets with different fishmeal levels (FM48, FM44, FM40, FM36, FM32) were established to determine the effects on largemouth bass growth performance, liver health and intestinal health. There were no significant differences in the percentage weight gain, specific growth rate, feed conversion rate, and condition factor of largemouth bass, but the hepatosomatic and viscerosomatic indexes were significantly decreased when the dietary fishmeal level was reduced to 40 %. The content of taurine, glycine, and histidine was significantly reduced in the muscle of largemouth bass fed the FM32 diet compared with those fed the FM48 and FM44 diets. Mixed protein feed reduced the total bile acid content and increased the low-density lipoprotein cholesterol content in the plasma of largemouth bass. The replacement of fishmeal with the mixed protein source inhibited the expression of tnf-α and caspase 3 and enhanced the expression of apoa1 in the liver, as well as enhancing the protein expression of FXR and SREBP and inhibiting the protein expression of P-PPARA in the liver. The intestinal pparα expression was suppressed when dietary fishmeal was replaced. When dietary fishmeal decreased, the mucosal folds height and muscle layer thickness also decreased. In conclusion, partial replacement of fishmeal with the mixed protein source did not affect the growth performance, while lipid metabolism and intestinal health were negatively affected when dietary fishmeal levels were below 36 %.

Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial.

(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood-brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; p = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin p = 0.031 [0.023, 0.579]; conjugated bilirubin p = 0.001 [0.193, 0.683]; unconjugated p = 0.387 [-0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood-brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood-brain barrier.

Elobixibat improves rectal sensation in patients with chronic constipation aged ≥60 years: a randomised placebo-controlled study

ObjectiveHigh rectal sensory thresholds (RSTs) are associated with chronic constipation (CC), especially in older patients. Bile acids (BAs) affect the RSTs of healthy individuals. Here, we aimed to investigate the...

Percutaneous transvenous coil embolization (PTCE) for treatment of single extrahepatic portosystemic shunt in dogs

BackgroundThere is limited information regarding percutaneous transvenous coil embolization (PTCE) for single extrahepatic portosystemic shunt (PSS). This study aimed to describe the procedure and outcome of PTCE in dogs with a single extrahepatic PSS. Forty-two privately owned dogs were included in this study. All dogs were diagnosed with extrahepatic PSS by computed tomography (CT). Preoperative CT images were used to evaluate the diameter of the PSS for coil placement. A multipurpose balloon catheter was percutaneously inserted into the PSS via the jugular vein, and transvenous retrograde portography (TRP) and measurement of blood pressure in the PSS (pPSS) were performed during balloon inflation; one or more embolization coils were implanted via the catheter.ResultsIn most cases, preoperative median fasting and postprandial serum total bile acid (TBA) concentrations were high (fasting, 86.5 μmol/L [ 3.7–250.0 μmol/L]; postprandial, 165.5 μmol/L [ 1.5–565.0 μmol/L]). CT revealed that 30 dogs had left gastrophrenic shunt; eight had left gastroazygos shunt; and one each had left gastrocaval, splenocaval, splenophrenic, and left colocaval shunt. TRP revealed that intrahepatic portal vascularity was clearly detectable in all dogs. The median values of pPSS before and during the balloon occlusion were 4.8 mmHg [2.0–13.0 mmHg] and 8.6 mmHg [5.0–18.0 mmHg], respectively. The median number and diameter of coils used were 2 coils [1 – 5 coils] and 8.0 mm [4.0 – 12.0 mm], respectively. The median times of irradiation and PTCE were 9 min [4–26 min] and 40 min [23–75 min], respectively. The median fasting and postprandial TBAs significantly decreased to 8.2 μmol/L [0.3–45.1 μmol/L, n = 38, p = 0.0028] and 19.8 μmol/L [0.3–106.7 μmol/L, n = 38, p = 0.0018], respectively, approximately 1 month after PTCE. The clinical success rate of PTCE without requirement for a second surgery was 95.2% (40/42 dogs). During revision surgery, one dog underwent surgical ligation and, in another dog, an ameroid constrictor was placed.ConclusionsPTCE was clinically effective in treating single extrahepatic PSS in dogs. Preoperative CT and TRP prior to PTCE might be clinically valuable for choosing the size of embolization coils, deciding the appropriate location of coil implantation, and estimating the number of coils to be implanted. PTCE is a promising alternative to conventional surgical procedures for single extrahepatic PSS in dogs.

Serum Bile Acids Concentrations and Liver Enzyme Activities after Low-Dose Trilostane in Dogs with Hyperadrenocorticism.

Hyperadrenocorticism (HAC) often leads to vacuolar hepatopathy. The impact of trilostane treatment on serum total bile acids (SBAs) concentrations in dogs with HAC remains unknown. This study investigated SBAs concentrations in healthy dogs and those with HAC following trilostane therapy. Ten healthy dogs and fifteen dogs with HAC were prospectively enrolled. A biochemistry profile and pre- and post-prandial SBAs concentrations were determined in each dog. Dogs with HAC were reassessed at 1 and 3 months after the initiation of trilostane treatment. Dogs with HAC had significantly higher serum ALT, ALP, and GGT activities, and cholesterol, triglyceride, and pre-prandial SBAs concentrations compared to healthy dogs. After 3 months of trilostane treatment, polyuria/polydipsia and polyphagia were completely resolved in 42.8% and 35.7%, respectively. Significant improvements in serum ALT and ALP activities and cholesterol concentrations were observed within 1-3 months of trilostane treatment. However, pre- and post-prandial SBAs concentrations did not significantly decrease. These findings suggest that treatment with low-dose trilostane for 3 months appears to reduce serum liver enzyme activities, but not SBAs concentrations. Further investigation is warranted to explore the effects of low-dose trilostane treatment on SBAs concentrations for a longer duration or after achieving appropriate post-ACTH cortisol levels.

Taurine-conjugated bile acids are the predominant form in hens and have potential impact on lipid metabolism in the liver

In mammals, bile acids composition varies with species, age, physiological conditions. However, the role of bile acids in the laying cycle of hens and their impact on lipid metabolism in chicken liver is not well understood. This study aimed to elucidate the role of bile acids in hen laying cycles, investigating their distribution across ages and assessing the impact of taurine-conjugated lithocholic acid (TLCA) on oleic acid-induced fatty liver cells in chickens. Results revealed an age-related increase in total bile acid concentration in hens blood, with taurine-conjugated bile acids prevailing. Among specific bile acids analysed, taurodeoxycholic acid (TDCA) decreased with age, while taurochenodeoxycholic acid (TCDCA) increased (n = 8). TLCA concentration also decreased gradually, while lycocholic acid (GCA) was elevated in 16-week-old hens (n = 8). Primary bile acids, cholic acid (CA), and chenodeoxycholic acid (CDCA) were higher at 16 weeks compared to egg production commencement (22 weeks) and 34 weeks (n = 8). Moreover, 5ß-Cholenic acid-7a-ol-3-one concentration was elevated in 74-week-old hens post-laying (n = 8). Investigating TLCA's impact on chicken liver lipid metabolism, TLCA significantly reduced lipid droplet accumulation, especially at 20 μM, while upregulating TLCA concentrations correlated with decreased SREBP1 protein expression responsible for triglyceride synthesis. In conclusion, taurine-conjugated bile acids potentially regulate lipid metabolism in hens, offering avenues for enhancing hens health and production through further mechanistic exploration and their potential integration into hens feed.

Per- and Poly-fluoroalkyl Substances and Bile Acid Profiles in Pregnant Women.

Alterations in bile acid (BA) profiles are closely associated with adverse outcomes in pregnant women and their offspring and may be one potential pathway underlying the related metabolic effects of per- and poly-fluoroalkyl substances (PFAS) exposure. However, evidence of associations between PFAS exposure and BA profiles in pregnant women is scarce. This study examined the associations of individual PFAS and PFAS mixture with BA profiles of pregnant women. We obtained quantitative data on the plasma concentrations of 13 PFAS and 15 BAs in 645 pregnant women from the Jiashan birth cohort. In Bayesian kernel machine regression models, the PFAS mixture was associated with increased plasma CA, TCA, TCDCA, and GLCA levels but with decreased GCA and LCA concentrations. Furthermore, the PFAS mixture was associated with increased concentrations of total BAs and the secondary/primary BA ratio but with decreased conjugated/unconjugated and glycine/taurine-conjugated BA ratios. PFHxS, PFUdA, PFOS, PFNA, and PFDA were the dominant contributors. The results of the linear regression analysis of individual PFAS were generally similar. Our findings provide the first epidemiological evidence for the associations of a PFAS mixture with BA profiles in pregnant women and may provide explanatory insights into the biological pathways underlying the related metabolic effects of PFAS exposure.

OR22-01 Sex Differences In Enterohepatic Circulation Mediated By Hepatic FXR And SHP Depletions In Mice

Abstract Disclosure: F. Reichardt: None. C. Galuke: None. S. Anakk: None. Bile acids are transported via the portal vein to the liver after their absorption through the distal intestine mucosa. In hepatocytes, they activate the nuclear receptors, Farnesoid-X-receptor (FXR) and Small Heterodimer Partner (SHP), which exert negative feedback on bile acids synthesis. The aim of this project is to decipher how hepatic FXR/SHP deletion impact BA composition, enterohepatic circulation, and its cross talk with the gut microbiota. Enterohepatic circulation was investigated by measuring total bile acids in intestinal, hepatic tissues and fecal tissues and in portal and systemic blood, using 3-5 months-old fed female and male wildtype (WT) and LDKO (liver specific FXR/SHP depletions) mice. We also examined if intestinal dysmotility mediated the alteration in bile acids absorption by following methylene blue dye progression in overnight fasted WT and LDKO mice. Portal and systemic total bile acids concentrations were higher in LDKO mice compared to WT, despite of no significant change in hepatic and intestinal levels. Sex differences were seen only in LDKO mice with higher systemic and portal concentrations in females compared to males. Intestinal transit time and fecal total bile acids were equivalent between all mice. Intriguingly, we observed that portal bile acids levels correlated to the liver weight to body weight ratio and to cecum weight to body weight ratio, suggesting that bile acids alterations within the enterohepatic loop could be associated to cecal dysbiosis. These preliminary findings highlight altered BA recirculation in LDKO mice compared to WT, but also between females and males LDKO. We hypothesize that these sex-specific modifications are associated with intestinal dysbiosis impacting bile acid compositions, and to test this we will be analyzing the influence of sex, and BA composition on the microbiome. Further investigations using fasted or HFD-fed LDKO and WT mice will help us to better understand the role of hepatic FXR and SHP in bile acids circulation between intestine and liver. Acknowledgement: University of Illinois Urbana-Champaign, American Cancer Society and Cancer Center at Illinois Seed grant Presentation: Saturday, June 17, 2023