Bile Acid Concentrations Research Articles

Liraglutide and Colesevelam Changes Serum and Fecal Bile Acid Levels in a Randomized Trial with Patients with Bile Acid Diarrhea.

Both liraglutide and colesevelam improve bile acid diarrhea (BAD) symptoms. Colesevelam binds excess amounts of diarrhea-causing bile acids in the colon whereas the mode of action for liraglutide remains elusive. Here, we examined the impact of colesevelam and liraglutide treatment on the concentrations of bile acids in serum and feces and the fecal microbiota composition to better understand the two drugs' modes of action. Bile acid species were analyzed in serum and fecal samples from a randomized, double-blind, double-dummy trial at baseline and after three and six weeks of orally administered colesevelam (1,875 mg twice daily, n = 26) or subcutaneously administered liraglutide (uptitrated by weekly increments of 0.6 mg from 0.6 to 1.8 mg daily, n = 26) in patients with 75selenium-homotaurocholic acid test-verified, idiopathic, or post-cholecystectomy BAD. Fecal microbiota composition was analyzed by 16S rRNA gene amplicon sequencing at the same time points. Colesevelam increased the fecal concentrations of all bile acid species while it decreased serum concentrations of secondary bile acids. Liraglutide induced a small increase in serum unconjugated bile acid concentrations without affecting fecal bile acid concentrations. No changes in fecal microbiota composition were observed with either treatment. Colesevelam and liraglutide exhibit distinct effects on serum and fecal bile acid concentrations with colesevelam reducing serum concentrations of secondary bile acids and promoting fecal bile acid excretion while liraglutide enhances serum concentrations of unconjugated bile acids, potentially through deceleration of small intestinal transit time allowing more time for passive absorption of bile acids.

Bile acids acting as a feeding signal and functional foods mimicking bile acid function.

To elucidate the function of the bile acid-binding receptor TGR5 in skeletal muscle, we developed transgenic mice expressing human TGR5 in the skeletal muscle tissue. A significant increase in muscle mass was observed in these transgenic mice, whereas a decrease in muscle mass was observed in the TGR5-deficient mice. Following treadmill exercise, TGR5 gene expression increased in response to ER stress induced in skeletal muscle via an ER stress response motif present in its promoter region. Exercise and rapid postprandial elevation in blood bile acid concentrations can be considered the primary stimuli for the TGR5-mediated increase in skeletal muscle mass. We developed a scoring system to identify food ingredients with TGR5 agonist activity, and identified the citrus limonoid nomilin. Similar effects were observed for other triterpenoids in addition to nomilin. Cell culture and in vivo experiments demonstrated that these food factors increase protein synthesis and muscle mass.

Additional criteria on scintigraphic testing for diagnosis of rapid colonic transit in patients with chronic diarrhea.

Colonic transit (CT) measured by validated scintigraphy using 111In-labeled activated charcoal particles is summarized using geometric center (GC) of isotopic distribution in four colonic regions and stool at 24 and 48 h. Diagnosis of rapid CT is currently based on GC24 ≥4.4 in females and >4.7 in males, which lack sensitivity. Our aim was to evaluate, in patients with chronic diarrhea with normal CT by GC24 and GC48, the diagnostic utility of CT change (∆GC) relative to sex-matched normal values. We evaluated two adult patient cohorts: 701 clinical patients (1994-2023) with chronic diarrhea and 76 research participants with irritable bowel syndrome with diarrhea (N = 63) or bile acid diarrhea (BAD, N = 13). Results of ∆GC were compared to 220 healthy controls' 95th percentiles (%ile) (≥2.0 females and ≥2.2 males). In the research cohort, we also analyzed (Spearman correlation) colonic ∆GC with ascending colon emptying T1/2 (AC T1/2), average stool frequency and consistency based on a daily diary, total fecal bile acid (BA) concentration, and % primary BA in a single stool sample. Among 701 clinical patients with normal GC24, 160 (22.3%) had rapid CT based on ∆GC 95th %ile in health. Among 76 research participants, an additional 20.6% IBS-D and 23% BAD had rapid CT ∆GC. Younger age and absence of diabetes mellitus were predictive of rapid ∆GC. ∆GC significantly correlated with AC T1/2 and with fecal BA. ∆GC identified an additional 21%-23% patients with rapid colonic transit among patients with diarrhea and normal GC24.

Effects of synergistic application of Viscozyme L–wet ball milling on structural, physicochemical and functional properties of insoluble dietary fiber from ginseng residue

Synergistic effect of Viscozyme L with wet ball milling treatment on structural, physicochemical and functional aspects of insoluble dietary fiber (IDF) from ginseng residue were examined. SEM examination showed that IDF extracted by Viscozyme L in conjunction with wet ball milling (WBE-IDF) exhibited loose microstructural arrangement, and particle size of WBE-IDF was much smaller than that of IDF extracted by Viscozyme L (E-IDF) and along IDF (untreated). The FTIR spectra demonstrated the variations in the peak intensities in three modified ginseng IDFs. Besides, the highest thermal stability and viscosity was displayed by WBE-IDF among examined samples. In addition, WBE-IDF has higher water and oil holding, water swelling, nitrite ion absorption, bile acid absorption, and glucose absorption capacities as compared to that of E-IDF and IDF. Overall results revealed that the Viscozyme L combined with wet ball milling extraction may change ginseng IDF structure, and improve its physicochemical and functional qualities, thereby providing a theoretical basis for food industry to produce good ginseng IDF.

Tauroursodeoxycholic Acid Improves Nonalcoholic Fatty Liver Disease by Regulating Gut Microbiota and Bile Acid Metabolism.

Tauroursodeoxycholic acid (TUDCA) is a synthetic bile salt that has demonstrated efficacy in the management of hepatobiliary disorders. However, its specific mechanism of action in preventing and treating nonalcoholic fatty liver disease (NAFLD) remains incompletely understood. This research revealed that TUDCA treatment can reduce obesity and hepatic lipid buildup, enhance intestinal barrier function and microbial balance, and increase the presence of Allobaculum and Bifidobacterium in NAFLD mouse models. TUDCA can influence the activity of farnesoid X receptor (FXR) and cholesterol 7α-hydroxylase (CYP7A1), resulting in higher hepatic bile acid levels and increased expression of sodium taurocholate cotransporting polypeptide (NTCP), leading to elevated concentrations of liver-bound bile acids in mice. Furthermore, TUDCA can inhibit the expression of FXR and fatty acid transport protein 5 (FATP5), thereby reducing fatty acid absorption and hepatic lipid accumulation. This investigation provides new insights into the potential of TUDCA for preventing and treating NAFLD.

Dietary supplementation of poly-dihydromyricetin-fused zinc nanoparticles alleviates fatty liver hemorrhagic syndrome by improving antioxidant capacity, intestinal health and lipid metabolism of laying hens

Fatty liver hemorrhagic syndrome is the main cause of noninfectious death of laying hens and results in substantial economic losses to the poultry industry. This study focused on evaluating the effects of Poly-dihydromyricetin-fused zinc nanoparticles (PDMY-Zn NPs) on antioxidant capacity, liver lipid metabolism, and intestinal health in laying hens. A total of 288 Jingfen laying hens (52 wk old) with similar body weights were randomly divided into 4 dietary groups with 6 replicates in each group for 8 wk. The control group received a basal diet, while the treatment groups were supplemented with PDMY-Zn NPs at levels of 200, 400, and 600 mg/kg, respectively. The results indicate that PDMY-Zn NPs supplementation can enhance antioxidant parameters (P < 0.05) in the blood and liver of laying hens. Simultaneously, it can mitigate vacuolar degeneration and inflammatory necrosis in hepatocytes, improve the relative expression level of related parameters associated with liver lipid metabolism and key regulatory genes (P < 0.05). Furthermore, it has been observed to reshape the composition and diversity of cecum microbes by increasing beneficial probiotics such as Lactobacillus and Prevotella, while also enhancing villi height and villi/crypt ratio in the duodenum and ileum (P < 0.05). Additionally, it elevates liver bile acid content along with the relative expression of key genes involved in liver synthesis (P < 0.05). In summary, PDMY-Zn NPs showed potential to alleviate fatty liver hemorrhagic syndrome by enhancing antioxidant capacity, regulating liver lipid metabolism, and maintaining intestinal health.

740. RABEPRAZOLE PROTECTS REFLUX ESOPHAGITIS DUE TO BILE IN RAT MODEL

Abstract Aims we studied the effect of proton pump inhibitor(PPI)(Rabeprazole) therapy on esophageal bile reflux in esophagitis after total gastrectomy. (Methodology) Sixteen 8-week old male Wistar rats were underwent total gastrectomy and esophagoduodenostomy to induce esophageal reflux of biliary and pancreatic juice. In 5 rats the sham operation induced a midline laparatomy alone (Sham). One week following surgery, they were treated with saline (Control) (n=8) PPI (Rabeprazole)(n=8)(30mg/kg/day) ip for 2 weeks. 3 weeks after operation, all rats were killed and the esophagus was evaluated histologically. Esophageal injury was evaluated by macroscopic, microscopic findings and expression of COX2 and PGE2. We performed the measurement of bile acid in the esophageal lumen and common bile duct. Results At 3 weeks after surgery, duodenal reflux induced esophageal erosions and ulcer formation. The macroscopic ulcer score and microscopic ulcer length were significantly reduced by PPI. The enhanced expression of COX2 and PGE2 in the control group was also markedly inhibited in the PPI group. Really, there is no difference between control group and PPI group in bile acid concentration from the common bile duct. PPI does not inhibit the secretion of bile acid from the common bile duct. But, the bile acid activity in the esophageal lumen was significantly increased in the control group, and this increase was significantly inhibited in the PPI group. Conclusion These results indicate that bile acid, which is inhibited by Rabeprazole, plays an important role in the mucosal damage induced by duodenal reflux.

Bariatric Surgery Is Associated with Lower Concentrations of Fecal Secondary Bile Acids and Their Metabolizing Microbial Enzymes: A Pilot Study.

Excess body fat elevates colorectal cancer risk. While bariatric surgery (BRS) induces significant weight loss, its effects on the fecal stream and colon biology are poorly understood. Specifically, limited data exist on the impact of bariatric surgery (BRS) on fecal secondary bile acids (BA), including lithocholic acid (LCA), a putative promotor of colorectal carcinogenesis. This cross-sectional case-control study included 44 patients with obesity; 15 pre-BRS (controls) vs. 29 at a median of 24.1months post-BRS.We examined the fecal concentrations of 11 BA by liquid chromatography and gene abundance of BA-metabolizing bacterial enzymes through fecal metagenomic sequencing. Differences were quantified using non-parametric tests for BA levels and linear discriminant analysis (LDA) effect size (LEfSe) for genes encoding BA-metabolizing enzymes. Total fecal secondary BA concentrations trended towards lower levels post- vs. pre-BRS controls (p = 0.07). Individually, fecal LCA concentrations were significantly lower post- vs. pre-BRS (8477.0 vs. 11,914.0 uM/mg, p < 0.008). Consistent with this finding, fecal bacterial genes encoding BA-metabolizing enzymes, specifically 3-betahydroxycholanate-3-dehydrogenase (EC 1.1.1.391) and 3-alpha-hydroxycholanate dehydrogenase (EC 1.1.1.52), were also lower post- vs. pre-BRS controls (LDA of - 3.32 and - 2.64, respectively, adjusted p < 0.0001). Post-BRS fecal BA concentrations showed significant inverse correlations with weight loss, a healthy diet quality, and increased physical activity. Concentrations of LCA, a secondary BA, and bacterial genes needed for BA metabolism are lower post-BRS. These changes can impact health and modulate the colorectal cancer cascade. Further research is warranted to examine how surgical alterations and the associated dietary changes impact bile acid metabolism.

Intestinal Stearoyl-CoA Desaturase-1 Regulates Energy Balance via Alterations in Bile Acid Homeostasis

Background and AimsStearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids into monounsaturated fatty acids and plays an important regulatory role in lipid metabolism. Previous studies have demonstrated that mice deficient in SCD1 are protected from diet-induced obesity and hepatic steatosis due to altered lipid assimilation and increased energy expenditure. Previous studies in our lab have shown that intestinal SCD1 modulates intestinal and plasma lipids and alters cholesterol metabolism. Here we investigated a novel role for intestinal SCD1 in the regulation of systemic energy balance. MethodsTo interrogate the role of intestinal SCD1 in modulating whole body metabolism, intestine- specific Scd1 knockout (iKO) mice were maintained on standard chow diet or challenged with a high-fat diet (HFD). Studies included analyses of bile acid content and composition, metabolic phenotyping including body composition, indirect calorimetry, glucose tolerance analyses, quantification of the composition of the gut microbiome, and assessment of bile acid signaling pathways. ResultsIKO mice displayed elevated plasma and hepatic bile acid content and decreased fecal bile acid excretion, associated with increased expression of the ileal bile acid uptake transporter, Asbt. In addition, the alpha and beta diversity of the gut microbiome was reduced in iKO mice, with several alterations in microbe species being associated with the observed increases in plasma bile acids. These increases in plasma bile acids were associated with increased expression of TGR5 targets, including Dio2 in brown adipose tissue and elevated plasma glucagon-like peptide-1 levels. Upon HFD challenge, iKO mice had reduced metabolic efficiency apparent through decreased weight gain despite higher food intake. Concomitantly, energy expenditure was increased, and glucose tolerance was improved in HFD-fed iKO mice. ConclusionOur results indicate that deletion of intestinal SCD1 has significant impacts on bile acid homeostasis and whole-body energy balance, likely via activation of TGR5.

Comprehensive Analysis of scRNA-Seq and Bulk RNA-Seq Reveals Transcriptional Signatures of Macrophages in Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a disorder that characterized by maternal pruritus, abnormal liver function, and an elevation in total bile acid concentrations during pregnancy. Immune factors have been recognized as playing a vital role in the mechanism of ICP. However, the underlying mechanisms regulating dysfunctional immune cells and immune genes remain to be fully elucidated. Single-cell RNA sequencing and bulk RNA sequencing data of the placenta were downloaded from the SRA database. The AUCell package, Monocle package and SCENIC package were utilized to explored immune cell activity, cell trajectory and transcription factor, respectively. GO, KEGG, and GSEA were employed to explore potential biological mechanisms. Cell-cell communications were further investigated using the CellChat package. RT-PCR, and Western blot were used to verify the gene expression in placenta. In placenta cells, macrophages were found to be significantly increased in ICP. Additionally, macrophages exhibited the highest immune gene score and were divided into four subclusters (MF1-4). Our analysis revealed significant elevations in MF2, associated with LPS response and antigen presentation, and MF4, associated with TNF and cytokine production. MF3 displayed an anti-inflammatory phenotype. MF1, closely related to ribosomes and proteins, exhibited a sharp decrease. Although ICP maintained an anti-inflammatory state, macrophage trajectories showed a gradual progression toward inflammation. Subsequently, we confirmed that cytokine- and chemokine-related signaling pathways were emphasized in macrophages. Within the CXCL signaling pathway, the increased expression of CXCL1 in macrophages can interact with CXCR2 in neutrophils, potentially inducing macrophage infiltration, stimulating neutrophil chemotaxis, and leading to an inflammatory response and cellular damage. In conclusion, we firstly revealed the transcriptional signatures of macrophages in ICP and discovered a tendency toward an inflammatory state. This study also provides new evidence that the CXCL1-CXCR2 axis may play an important role in the pathogenesis of ICP.

Laminaria japonica Polysaccharide Regulates Fatty Hepatosis Through Bile Acids and Gut Microbiota in Diabetes Rat.

In this study, we examined the effect of Laminaria japonica polysaccharide (fucoidan) on the regulation of lipid metabolism. A rat model of diabetes mellitus (DM) was established by a high-sugar and high-fat diet combined with streptozotocin. Changes in the rats' body weight and blood glucose level during the experiment were recorded. Before the end of the experiment, an automatic biochemical analyzer was used to detect the fasting blood glucose (FBG), lipid content in serum, and insulin content, and calculate the insulin resistance index. Oil red O staining was used to detect lipid deposition in the liver. H&E staining, Masson staining, and PASM staining were used to observe the pathological structural changes in the liver. 16s RNA sequencing and targeted metabolomics were used to detect intestinal microbiota and bile acid content. The results showed that fucoidan was able to inhibit weight loss in the DM rats and reduce the content of triglycerides (TG), cholesterol (TC), and low-density lipoprotein (LDL-C) in serum. Oil red O staining showed a decrease in liver fat accumulation after fucoidan treatment. 16s RNA sequencing demonstrated that fucoidan increased the abundance of Bacteroidia, Campylobacteria, Clostridia, Gammaproteobacteria, Negativicutes, and Verrucomicrobi. Fucoidan also increased the secretion of secondary bile acids (Nor-DCA, TLCA, β-UDCA) and alleviated lipid metabolism disorders. The expression of α-SMA was inhibited by fucoidan, whereas the expression of FXR and TGR5 was promoted. Fucoidan shows good activity in regulating lipid metabolism by regulating the expression of FXR and TGR5 and acting on the intestinal flora-bile acid axis.

Assessment of Fetal Ventricular Size and Shape in Women With Intrahepatic Cholestasis of Pregnancy Using Speckle Tracking.

To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. This case-control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24-segment spherical indices (SIs) were measured and compared between groups. The routine fetal cardiac parameters, global and right-ventricular SIs did not differ between the ICP and control groups. The left-ventricular apical (segments 16-24) SIs were lower in the ICP group than in the control group (P < .05), with no significant difference in the other left-ventricular segments. Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty-four-segment SIs can be used to effectively evaluate these changes.

Effects of wheat-based fermented liquid feed on growth performance, nutrient digestibility, gut microbiota, intestinal morphology, and barrier function in grower-finisher pigs.

Fermented liquid feed (FLF) can improve dietary nutrient absorption levels, degrade anti-nutrient factors in diets, and increase beneficial bacteria abundance in animal guts. However, few systematic studies have been conducted on WFLF in pigs. The present study evaluates the effects of WFLF on the growth performance, nutrient digestibility, gastric volume, intestinal morphology, intestinal health, intestinal barrier function, serum biochemical immunity, gut microbiota, and intestinal microbial diversity of grower-finisher pigs. In total, 80 weaned pigs were randomly allocated to two treatment groups based on their initial body weight: a basal diet with pellet dry feeding (CON) and a basal diet with wheat-based fermented liquid feed (WFLF), with four replicate pens per group. The experiment lasted 82 d. Compared with CON pigs, those fed WFLF were heavier significantly at 60-82 d and had significantly higher average daily feed intake, average daily gain, and gain: feed ratio at 60-82 d and 1-82 d. WFLF pigs had significantly greater jejunum, total tract, and ileal digestibility for all nutrients and amino acids, excluding arginine, than CON pigs. WFLF intake influenced villus height, villus height: crypt depth ratio of the anterior segment of the jejunum(A-jejunum), crypt depth, and redox potential of the posterior segment of the jejunum (P-jejunum) while significantly affecting body weight. Additionally, FLF improved gastric capacity significantly. Furthermore, mRNA expression of occludin and claudin-1 in the mucosa of the ileum and jejunum was significantly higher in WFLF pigs than in CON pigs. WFLF increased serum concentrations of alanine transaminase and reduced low-density lipoprotein cholesterol, total cholesterol, and total bile acid content. The alpha diversity (Shannon and Simpson indices) in the stomachs of WFLF pigs was significantly higher than in CON pigs. Microbial diversity in the stomach, ileum, and cecum, as well as the abundance of lactic acid bacteria, were increased in WFLF pigs compared to CON pigs. In conclusion, WFLF intake may positively influence intestinal ecology by improving digestive tract structure, upregulating intestinal barrier-related genes, and improving intestinal morphology to enhance intestinal digestive function and health. Collectively, the present study shows that WFLF intake can increase growth performance while maintaining beneficial nutrient digestibility in grower-finisher pigs.

Bile Acid Composition and Transcriptome Analysis of the Liver and Small Intestine in Different Species.

Bile, a crucial fluid produced continuously by the liver, plays an essential role in digestion within the small intestine. Beyond its primary function in lipid digestion, bile also acts as a pathway for the elimination of various endogenous and exogenous substances. There have been limited studies focusing on interspecies differences. This study offers a comprehensive analysis of bile acid (BA) composition and its correlation with gene expression patterns across six different species, including mammals and poultry, through combining Liquid Chromatography-Mass Spectrometry (LC-MS) and transcriptome sequencing. The BA profiles revealed distinct metabolite clusters: D-glucuronic acid (GLCA) and glycochenodeoxycholic acid (GCDCA) were predominant in mammals, while taurolithocholic acid (TLCA) and T-alpha-MCA were prevalent in poultry, highlighting species-specific BA compositions. Differentially abundant metabolites, particularly GDCA, glycohyodeoxycholic acid (GHDCA) and taurodeoxycholic acid (TDCA) showed significant variations across species, with pigs showing the highest BA content. Transcriptome analysis of the liver and small intestine tissues of 56 cDNA libraries across the six species revealed distinct mRNA expression patterns. These patterns clustered samples into broad categories based on tissue type and phylogenetic relationships. Furthermore, the correlation between gene expression and BA content was examined, identifying the top 20 genes with significant associations. These genes potentially serve as biomarkers for BA regulation.

Multi-Omics Analysis Reveals Dietary Fiber's Impact on Growth, Slaughter Performance, and Gut Microbiome in Durco × Bamei Crossbred Pig.

Dietary fiber (DF) is an important nutrient component in pig's diet that remarkably influences their growth and slaughter performance. The ability of pigs to digest DF depends on the microbial composition of the intestinal tract, particularly in the hindgut. However, studies on how DF alters the growth and slaughter performance of pigs by shaping the gut microbial composition and metabolites are still limited. Therefore, this study aimed to investigate the effects of DF on microbial composition, functions, and metabolites, ultimately altering host growth and slaughter performance using Durco × Bamei crossbred pigs supplemented with 0%, 10%, 17%, and 24% broad bean silage in the basic diet. We found that the final weight, average daily gain, fat, and lean meat weight significantly decreased with increasing DF. Pigs with the lowest slaughter rate and fat weight were observed in the 24% fiber-supplemented group. Gut microbial communities with the highest alpha diversity were formed in the 17% fiber group. The relative abundance of fiber-degrading bacteria, bile acid, and succinate-producing bacteria, including Prevotella sp., Bacteroides sp., Ruminococcus sp., and Parabacteroides sp., and functional pathways, including the butanoate metabolism and the tricarboxylic acid [TCA] cycle, significantly increased in the high-fiber groups. The concentrations of several bile acids significantly decreased in the fiber-supplemented groups, whereas the concentrations of succinate and long-chain fatty acids increased. Our results indicate that a high-fiber diet may alter the growth and slaughter performance of Durco × Bamei crossbred pigs by modulating the composition of Prevotella sp., Bacteroides sp., Ruminococcus sp., Parabacteroides sp., and metabolite pathways of bile acids and succinate.

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

Exploring the effects of dietary cholesterol on growth, immunity, and lipid metabolism of juvenile Chinese mitten crabs (Eriocheir sinensis)

This study aims to investigate the nutritional needs and physiological functions of dietary cholesterol in juvenile Chinese mitten crabs (Eriocheir sinensis). In the 8-week feeding experiment, we evaluated the effects of various cholesterol levels (0 control, 0.6, 1.3, 2.6, 5.9, 12.0 g/kg diet) on growth, immune capacity, lipid metabolism, molting, and cholesterol and bile acid metabolism. Crabs (1.06 ± 0.04 g) were divided into six groups with four replicates of 40 crabs per tank. The highest weight gain was found in crabs fed 5.9 g/kg cholesterol (P < 0.05), while the highest molting frequency was observed in the 0.6 g/kg group (P < 0.05). Cholesterol significantly changed fatty acid composition in the hepatopancreas, and 5.9 g/kg cholesterol increased immune enzyme activities (acid phosphatase, alkaline phosphatase, and polyphenol oxidase) (P < 0.05). A 5.9 g/kg cholesterol significantly upregulated lipogenesis- and catabolism-related genes, while higher levels of cholesterol (12.0 g/kg) downregulated lipogenesis-related genes significantly (P < 0.05). Low cholesterol levels upregulated chitinase expression, while ecdysone receptor and molt-inhibiting hormone expressions were upregulated with cholesterol levels (P < 0.05). Cholesterol also upregulated the gene in bile acid metabolism. The total bile acids, the proportion of primary bile acids, and the content of primary bile acids increased significantly compared to the control. Based on quadratic regression model analysis, the optimal dietary cholesterol level for juvenile E. sinensis is 5.74–5.77 g/kg. The study suggests that cholesterol promotes growth and immunity in juvenile E. sinensis by regulating molting frequency, improving lipid and HUFA utilization, and increasing bile acids.

Astragalus polysaccharides-induced gut microbiota play a predominant role in enhancing of intestinal barrier function of broiler chickens

BackgroundThe intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota. Astragalus polysaccharides (APS) have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function. The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.ResultsDietary polysaccharide deprivation induced intestinal barrier dysfunction, decreased growth performance, altered microbial composition (Faecalibacterium, Dorea, and Coprobacillus), and reduced isobutyrate concentration. The results showed that APS facilitates intestinal barrier function in broiler chickens, including a thicker mucus layer, reduced crypt depth, and the growth of tight junction proteins. We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides, a commensal bacterium that plays a predominant role in enhancing intestinal barrier function. An in vitro growth assay further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis. Dietary APS supplementation increased the concentrations of isobutyrate and bile acid (mainly chenodeoxycholic acid and deoxycholate acid) and activated signaling pathways related to intestinal barrier function (such as protein processing in the endoplasmic reticulum, tight junctions, and adherens junction signaling pathways).ConclusionsAPS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis, and increasing the concentrations of isobutyrate and bile acids (mainly CDCA and DCA). These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.Graphical

The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC

ABSTRACT The role of the gut microbiota in the occurrence and progression of primary biliary cholangitis (PBC) is not fully understood. First, the fecal microbiota of patients with PBC (n = 4) (PBC-FMT) or healthy individuals (n = 3) (HC-FMT) was transplanted into pseudo germ-free mice or 2OA-BSA–induced PBC models. The functions, histology and transcriptome of the liver, and microbiota and metabolome of the feces were analyzed. Second, the liver transcriptomes of PBC patients (n = 7) and normal individuals (n = 7) were analyzed. Third, the liver transcriptomes of patients with other liver diseases were collected from online databases and compared with our human and mouse data. Our results showed that PBC-FMT increased the serum ALP concentration, total bile acid content, liver injury and number of disease-related pathways enriched with upregulated liver genes in pseudo germ-free mice and increased the serum glycylproline dipeptidyl aminopeptidase level and liver damage in a 2OA-BSA–induced PBC model. The gut microbiota and metabolome differed between PBC-FMT and HC-FMT mice and reflected those of their donors. PBC-FMT tended to upregulate hepatic immune and signal transduction pathways but downregulate metabolic pathways, as in some PBC patients. The hematopoietic cell lineage, Toll-like receptor, and PPAR signaling pathway were not affected in patients with alcoholic hepatitis, HBV, HCV, HCV cirrhosis, or NASH, indicating their potential roles in the gut microbiota affecting PBC. In conclusion, the altered gut microbiota of PBC patients plays an important role in the occurrence and progression of PBC. The improvement of the gut microbiota is worthy of in-depth research and promotion as a critical aspect of PBC prevention and treatment.

Abstract Mo041: Bile Acid Dysregulation in Response to Right Heart Failure and Hepatic Congestion

Introduction: Right heart failure (RHF), the result of impaired RV contractility and/or severe right-sided valvulopathies, is a clinical syndrome that commonly results in chronically elevated central venous pressures and hepatic congestion. Hepatic dysfunction in patients with heart failure portends a poor prognosis. In part, this may be due to the liver’s pivotal role in bile acid synthesis and processing. In addition to the classic role of a digestive surfactant, bile acids serve as important and dynamic signaling molecule. The present study characterizes a unique bile acid profile found in patients with RHF. Research Question: We hypothesize that RHF and hepatic congestion results in a dysregulation of bile acids. These untoward changes in bile acids concentrations may provide both important prognostic value and novel mechanistic pathways in congestive liver disease. Aims: 1) To characterize systemic and hepatic vein bile acid concentrations in patients with right heart failure. 2) To phenotype a mouse model of hepatic congestion and understand the mechanistic effects of specific bile acids on liver biology Methods: We enrolled a total of 60 patients who were referred for right heart catheterization (RHC). Patient demographics, echocardiograms, and routine laboratory tests were captured at enrollment. Blood was sampled from the IVC and hepatic vein during RHC. Bile acids were quantified from serum using liquid chromatography-tandem mass spectrometry. To model hepatic congestion, mice underwent ligation of the IVC. Blood and tissue samples were harvested and underwent mass spectrometry evaluation for the bile acid composition and immunohistochemistry was performed to characterize the immune landscape, respectively. Results: We captured a total of 12 control samples from patients with normal filling pressures, 25 patients with left heart failure (LHF), and 23 patients with RF. Patients with RHF had poorer survival outcomes compared to control or LHF. Patients with RHF had significant increases in specific conjugated bile acids when compared to control or LHF (Figure 1). Conclusions: In this study, we identified several conjugated bile acids that are uniquely elevated in patients with RHF compared to LHF and control. Additionally, patients with RHF had poorer survival. Collectively, these data suggest bile acids may serve as important biomarkers and signaling molecules in the pathogenesis of cardiogenic liver disease.