A comparison study on structure-function relationship of polysaccharides obtained from sea buckthorn berries using different methods:antioxidant and bile acid-binding capacity

In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells

BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Bioactivities,Mechanisms,Production,and Potential Application of Bile Acids in Preventing and Treating Infectious Diseases

Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and energy.Bile acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary diseases.Notably,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and spasm.In recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific community.This paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious diseases.Compared with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality.In addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic synthesis.Finally,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids.The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets

Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previous work demonstrated the protective effect of OA on intestinal health,but the underlying molecular mechanisms remain unclear.This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli(ETEC)in piglets.The key molecular role of bile acid receptor signaling in this process has also been explored.Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets(P<0.05).OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum(P<0.05).This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets.In addition,as a natural ligand of bile acid receptors,OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-PKA-CREB signaling pathway(P<0.05).Furthermore,OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR(P<0.05),thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells.Conclusions In conclusion,our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response,which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.

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

Background 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.Results We randomly divided eighteen healthy primiparity lactating dairy goats(days in milk=100±6 d)into two groups and supplemented them with 0 or 4 g/d of BAs undergoing 5 weeks 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 Christensenellaceae R-7 group)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.Conclusion 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.

Detection and analysis of serum bile acid profile in patients with colonic polyps

BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.

Oligomeric procyanidins combined with Parabacteroides distasonis ameliorate high-fat diet-induced atherosclerosis by regulating lipid metabolism,inflammation reaction and bile acid metabolism in ApoE^(-/-)mice

Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids(BAs)profile.Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS,whose antiatherosclerotic effect may be associated with the promotion of gut probiotics.However,it remains unclear whether and how oligomeric procyanidins and P.distasonis combined(PPC)treatment can effectively alleviate high-fat diet(HFD)-induced AS.In this study,PPC treatment was found to significantly decrease atherosclerotic lesion,as well as alleviate the lipid metabolism disorder,inflammation and oxidative stress injury in ApoE^(-/-)mice.Surprisingly,targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs,and increased fecal BAs excretion.Further,quantitative polymerase chain reaction(qPCR)analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression;In addition,PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor(FXR)pathway,thus exhibiting a significant serum cholesterol-lowering effect.In summary,PPC attenuated HFD-induced AS in ApoE^(-/-)mice,which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

Hepatic protein phosphatase 1 regulatory subunit 3G alleviates obesity and liver steatosis by regulating the gut microbiota and bile acid metabolism

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12a-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiotadependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7a-hydroxylase(CYP7A1)and sterol-12a-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-a hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential therapeutic targets for obesity-related disorders.

Saikosaponin D improves nonalcoholic fatty liver disease via gut microbiota-bile acid metabolism pathway

Non-alcoholic fatty liver disease(NAFLD)is the main cause of chronic liver disease worldwide.Bupleurum is widely used in the treatment of non-alcoholic fatty liver,and saikosaponin D(SSD)is one of the main active components of Bupleurum.The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on“gut-liver axis”.Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice,improved insulin sensitivity,and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase(AST)and alanine aminotransferase(ALT).Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor(Fxr),small heterodimer partner(Shp),recombinant fibroblast growth factor 15(Fgf15)and apical sodium dependent bile acid transporter(Asbt)in the intestine,suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling.SSD can significantly reduce the gut microbiota associated with bile salt hydrolase(BSH)expression,such as Clostridium.Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids,thereby inhibiting the intestinal FXR.These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acidintestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.RESULTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal.Additionally,ursodeoxycholic acid(UDCA)can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concen-tration in bile.Despite these treatment options,there are still patients who experience stone recurrence.The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People’s Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected.According to the post-ERCP treatment plan,100 patients were classified into UDCA(n=47)and control(n=53)groups.We aimed to assess the clinical efficacy and rate of relapse in the two patient populations.We then collected information(basic demographic data,clinical characteristics,and serum biochemical indicators)and determined the factors contributing to relapse using logistic regression analysis.Our secondary goal was to determine the effects of UDCA on liver function after ERCP.Compared to the control group,the UDCA group demonstrated a higher clinical effectiveness rate of 92.45%vs 78.72%(P<0.05).No significant differences were observed in liver function indices,including total bilirubin,direct bilirubin,gamma-glutamyl transpeptidase,alanine aminotransferase,alkaline phosphatase,and aspartate aminotransferase,between the two groups before treatment.After treatment,all liver function indices were significantly reduced.Comparing the control vs UDCA groups,the UDCA group exhibited significantly lower levels of all indices(55.39±6.53 vs 77.31±8.52,32.10±4.62 vs 45.39±5.69,142.32±14.21 vs 189.63±16.87,112.52±14.25 vs 149.36±15.36,122.61±16.00 vs 171.33±22.09,96.98±10.44 vs 121.35±11.57,respectively,all P<0.05).The stone recurrence rate was lower in the UDCA group(13.21%)in contrast with the control group(44.68%).Periampullary diverticula(OR:6.00,95%CI:1.69-21.30),maximum stone diameter(OR:1.69,95%CI:1.01-2.85),stone quantity>3(OR:4.23,95%CI:1.17-15.26),and positive bile culture(OR:7.61,95%CI:2.07-27.91)were independent factors that influenced the relapse of common bile duct stones after ERCP(P<0.05).Furthermore,postoperative UDCA was identified as a preventive factor(OR:0.07;95%CI:0.08-0.09).CONCLUSION The intervention effect of UDCA after ERCP for common bile duct stones is adequate,providing new research directions and references for the prevention and treatment of stone recurrence.

Bile acid receptors and nonalcoholic fatty liver disease

With the high prevalence of obesity, diabetes, and otherfeatures of the metabolic syndrome in United States, nonalcoholic fatty liver disease(NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis(NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor(FXR) and transmembrane G protein-coupled receptor(TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH.

Comparative evaluation of intragastric bile acids and hepatobiliary scintigraphy in the diagnosis of duodenogastric reflux

AIM:To assess the diagnostic value of a combination of intragastric bile acids and hepatobiliary scintigraphy in the detection of duodenogastric reflux(DGR).METHODS:The study contained 99 patients with DGR and 70 healthy volunteers who made up the control group.The diagnosis was based on the combination of several objective arguments:a long history of gastric symptoms(i.e.,nausea,epigastric pain,and/or bilious vomiting) poorly responsive to medical treatment,gastroesophageal reflux symptoms unresponsive to protonpump inhibitors,gastritis on upper gastrointestinal(GI) endoscopy and/or at histology,presence of a bilious gastric lake at > 1 upper GI endoscopy,pathologic 24-h intragastric bile monitoring with the Bilitec device.Gas-tric juice was aspirated in the GI endoscopy and total bile acid(TBA),total bilirubin(TBIL) and direct bilirubin(DBIL) were tested in the clinical laboratory.Continuous data of gastric juice were compared between each group using the independent-samples Mann-Whitney U-test and their relationship was analysed by Spearman's rank correlation test and Fisher's linear discriminant analysis.Histopathology of DGR patients and 23 patients with chronic atrophic gastritis was compared by clinical pathologists.Using the Independent-samples Mann-Whitney U-test,DGR index(DGRi) was calculated in 28 patients of DGR group and 19 persons of control group who were subjected to hepatobiliary scintigraphy.Receiver operating characteristic curve was made to determine the sensitivity and specificity of these two methods in the diagnosis of DGR.RESULTS:The group of patients with DGR showed a statistically higher prevalence of epigastric pain in comparison with control group.There was no significant difference between the histology of gastric mucosa with atrophic gastritis and duodenogastric reflux.The bile acid levels of DGR patients were significantly higher than the control values(Z:TBA:-8.916,DBIL:-3.914,TBIL:-6.197,all P < 0.001).Two of three in the DGR group have a significantly associated with each other(r:TBA/DBIL:0.362,TBA/TBIL:0.470,DBIL/TBIL:0.737,all P < 0.001).The Fisher's discriminant function is followed:Con:Y = 0.002TBA + 0.048DBIL + 0.032TBIL 0.986;Reflux:Y = 0.012TBA + 0.076DBIL + 0.089TBIL-2.614.Eighty-four point zero five percent of original grouped cases were correctly classified by this method.With respect to the DGR group,DGRi were higher than those in the control group with statistically significant differences(Z =-5.224,P < 0.001).Twenty eight patients(59.6%) were deemed to be duodenogastric reflux positive by endoscopy,as compared to 37 patients(78.7%) by hepatobiliary scintigraphy.CONCLUSION:The integrated use of intragastric bile acid examination and scintigraphy can greatly improve the sensitivity and specificity of the diagnosis of DGR.

Ursodeoxycholic acid combined with percutaneous transhepatic balloon dilation for management of gallstones after elimination of common bile duct stones

AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct(CBD) stones.METHODS From April 2014 to May 2016, 15 consecutive patients(6 men and 9 women) aged 45-86(mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain(n = 1), abdominal distension(n = 1), and fever(n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.

Role of bile acids in the regulation of the metabolic pathways

Recent studies have revealed that bile acids(BAs)are not only facilitators of dietary lipid absorption but also important signaling molecules exerting multiple physiological functions.Some major signaling pathways involving the nuclear BAs receptor farnesoid X receptor and the G protein-coupled BAs receptor TGR5/M-BAR have been identified to be the targets of BAs.BAs regulate their own homeostasis via signaling pathways.BAs also affect diverse metabolic pathways including glucose metabolism,lipid metabolism and energy expenditure.This paper suggests the mechanism of controlling metabolism via BA signaling and demonstrates that BA signaling is an attractive therapeutic target of the metabolic syndrome.

Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

Bile acids(BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor(FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins(VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-Ⅱ, very low-density lipoproteins receptor(VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-Ⅲ, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea(BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment.

High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

AIM： To investigate whether high-fat-feeding is associ- ated with increased intestinal permeability via altera- tions in bile acid metabolism.METHODS： Male C57BI/6J mice were fed on a high-fat （n = 26） or low-fat diet （n = 24） for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile ac- ids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor （FXR） and tumor necrosis factor

Role of bile acids in colon carcinogenesis

Bile acids(BAs)are cholesterol derivatives synthesized in the liver and then secreted into the intestine for lipid absorption.There are numerous scientific reports describing BAs,especially secondary BAs,as strong carcinogens or promoters of colon cancers.Firstly,BAs act as strong stimulators of colorectal cancer(CRC)initiation by damaging colonic epithelial cells,and inducing reactive oxygen species production,genomic destabilization,apoptosis resistance,and cancer stem cells-like formation.Consequently,BAs promote CRC progression via multiple mechanisms,including inhibiting apoptosis,enhancing cancer cell proliferation,invasion,and angiogenesis.There are diverse signals involved in the carcinogenesis mechanism of BAs,with a major role of epidermal growth factor receptor,and its down-stream signaling,involving mitogen-activated protein kinase,phosphoinositide 3-kinase/Akt,and nuclear factor kappa-light-chain-enhancer of activated B cells.BAs regulate numerous genes including the human leukocyte antigen class I gene,p53,matrix metalloprotease,urokinase plasminogen activator receptor,Cyclin D1,cyclooxygenase-2,interleukin-8,and miRNAs of CRC cells,leading to CRC promotion.These evidence suggests that targeting BAs is an efficacious strategies for CRC prevention and treatment.