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The Journal of Clinical Investigation Jan 2020Excessive fecal bile acid (BA) loss causes symptoms in a large proportion of people diagnosed with irritable bowel syndrome with diarrhea, a common functional bowel...
Excessive fecal bile acid (BA) loss causes symptoms in a large proportion of people diagnosed with irritable bowel syndrome with diarrhea, a common functional bowel disorder. This BA diarrhea (BAD) results from increased hepatic synthesis of BAs, with impaired negative feedback regulation by the ileal hormone fibroblast growth factor 19 (FGF19). In this issue of the JCI, Zhao et al. investigated BA metabolism, including fecal BAs, serum BAs, and FGF19, in patients and controls. They identified associations between fecal bacterial BA metabolism and specific microbiota, especially Clostridium scindens. These findings have been tested in a mouse model using microbiota transplants and antibiotic treatment. This group of organisms has potential as a biomarker for BAD and to be a target for therapy.
Topics: Animals; Bile; Bile Acids and Salts; Clostridiales; Diarrhea; Fibroblast Growth Factors; Humans; Irritable Bowel Syndrome; Mice; Microbiota
PubMed: 31815741
DOI: 10.1172/JCI133117 -
Nature Communications Jun 2023Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and correlate with alterations in dietary fat and body weight, but the...
Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and correlate with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. To address this knowledge gap, we characterize a diverse set of mouse- and human-derived Turicibacter isolates, and find they group into clades that differ in their transformations of specific bile acids. We identify Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Using male and female gnotobiotic mice, we find colonization with individual Turicibacter strains leads to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium exogenously expressing bile-modifying genes from Turicibacter strains decreases serum cholesterol, triglycerides, and adipose tissue mass. This identifies genes that enable Turicibacter strains to modify host bile acids and lipid metabolism, and positions Turicibacter bacteria as modulators of host fat biology.
Topics: Male; Humans; Female; Mice; Animals; Bile Acids and Salts; Gastrointestinal Microbiome; Dietary Fats; Bile; Bacteria; Tenericutes; Mammals
PubMed: 37339963
DOI: 10.1038/s41467-023-39403-7 -
World Journal of Gastroenterology Mar 2024Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common... (Review)
Review
Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.
Topics: Infant; Child; Infant, Newborn; Humans; Bile Ducts; Biliary Atresia; Choledochal Cyst; Bile Duct Diseases; Cholangiography
PubMed: 38577180
DOI: 10.3748/wjg.v30.i9.1043 -
Materials (Basel, Switzerland) Dec 2021Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary,... (Review)
Review
Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary, pancreatic, and gastrointestinal surgery can inadvertently cause iatrogenic BDI. The commonly utilized clinical treatment of BDI is biliary-enteric anastomosis. However, removal of the Oddi sphincter, which serves as a valve control over the unidirectional flow of bile to the intestine, can result in complications such as reflux cholangitis, restenosis of the bile duct, and cholangiocarcinoma. Tissue engineering and biomaterials offer alternative approaches for BDI treatment. Reconstruction of mechanically functional and biomimetic structures to replace bile ducts aims to promote the ingrowth of bile duct cells and realize tissue regeneration of bile ducts. Current research on artificial bile ducts has remained within preclinical animal model experiments. As more research shows artificial bile duct replacements achieving effective mechanical and functional prevention of biliary peritonitis caused by bile leakage or obstructive jaundice after bile duct reconstruction, clinical translation of tissue-engineered bile ducts has become a theoretical possibility. This literature review provides a comprehensive collection of published works in relation to three tissue engineering approaches for biomimetic bile duct construction: mechanical support from scaffold materials, cell seeding methods, and the incorporation of biologically active factors to identify the advancements and current limitations of materials and methods for the development of effective artificial bile ducts that promote tissue regeneration.
PubMed: 34885623
DOI: 10.3390/ma14237468 -
Frontiers in Immunology 2022Bile duct, pancreatic, and gastric cancers are deadly digestive system tumors with high malignancy and poor patient prognosis. The efficiencies of conventional surgical... (Review)
Review
Bile duct, pancreatic, and gastric cancers are deadly digestive system tumors with high malignancy and poor patient prognosis. The efficiencies of conventional surgical treatment, radiation therapy, and chemotherapy are limited. In contrast, chimeric antigen receptor (CAR) T-cell therapy represents a landmark therapeutic approach to antitumor immunity with great efficacy in treating several hematological malignancies. CAR T-cell therapy involves genetically engineering the expression of specific antibodies based on the patient's T-cell surface and amplifying these antibodies to identify and target tumor-associated antigens. CAR T-cell therapy can effectively inhibit disease progression and improve the survival of patients with bile duct, pancreatic, and gastric cancers. The effectiveness of CAR T cells in tumor therapy can be validated using xenograft models, providing a scientific testing platform. In this study, we have reviewed the progress in CAR T-cell production and its development, focusing on the current status and optimization strategies for engineered CAR T cells in the bile duct, pancreatic, and gastric cancers.
Topics: Humans; Immunotherapy, Adoptive; Stomach Neoplasms; Bile; T-Lymphocytes; Pancreatic Ducts
PubMed: 36341440
DOI: 10.3389/fimmu.2022.1025608 -
Journal of Food Protection Mar 2022In this study, the distribution of hygienic indicator bacteria in cattle livers and bile was examined at slaughterhouses. One hundred twenty-seven cattle livers with...
ABSTRACT
In this study, the distribution of hygienic indicator bacteria in cattle livers and bile was examined at slaughterhouses. One hundred twenty-seven cattle livers with gallbladders were carefully eviscerated from carcasses at 10 slaughterhouses. Microbiological examination revealed that nine bile samples (7.1% prevalence) and 19 liver parenchyma samples (15.0% prevalence) were positive for Enterobacteriaceae (EB) with means ± standard deviations of 3.68 ± 4.63 log CFU/mL and 1.59 ± 2.47 log CFU/g, respectively; thus, bacterial contamination was apparent even at the postevisceration stage. Subsequently, 70 cattle livers were obtained at the postprocessing and storage stage from 7 of the 10 slaughterhouses. Microbiological analysis revealed significantly higher levels of EB in the liver parenchyma (3.00 ± 3.89 log CFU/g, P = 0.011) than those at the postevisceration stage, suggesting that bacterial dissemination and/or replication occurred in the liver parenchyma during processing and storage. According to 16S rRNA ion semiconductor sequencing analysis of representative samples from 12 cattle, Proteobacteria, Firmicutes, and Actinobacteria were dominant in both the parenchyma and bile in which EB and Escherichia coli were predominant among livers with higher EB levels. These results suggest that bile plays a role as a vehicle for bacterial transmission to the liver parenchyma. This study is the first to evaluate bacterial distribution and community structure in the liver and biliary microecosystem of cattle at slaughter. Our data support the use of EB testing of bile to screen cattle livers contaminated with high levels of fecal indicator bacteria.
Topics: Abattoirs; Animals; Bile; Cattle; Colony Count, Microbial; Enterobacteriaceae; Food Contamination; Food Microbiology; Liver; Meat; RNA, Ribosomal, 16S
PubMed: 34818425
DOI: 10.4315/JFP-21-288 -
EMBO Reports Dec 2023Mitochondrial and peroxisomal anchored protein ligase (MAPL) is a dual ubiquitin and small ubiquitin-like modifier (SUMO) ligase with roles in mitochondrial quality...
Mitochondrial and peroxisomal anchored protein ligase (MAPL) is a dual ubiquitin and small ubiquitin-like modifier (SUMO) ligase with roles in mitochondrial quality control, cell death and inflammation in cultured cells. Here, we show that MAPL function in the organismal context converges on metabolic control, as knockout mice are viable, insulin-sensitive, and protected from diet-induced obesity. MAPL loss leads to liver-specific activation of the integrated stress response, inducing secretion of stress hormone FGF21. MAPL knockout mice develop fully penetrant spontaneous hepatocellular carcinoma. Mechanistically, the peroxisomal bile acid transporter ABCD3 is a primary MAPL interacting partner and SUMOylated in a MAPL-dependent manner. MAPL knockout leads to increased bile acid production coupled with defective regulatory feedback in liver in vivo and in isolated primary hepatocytes, suggesting cell-autonomous function. Together, our findings establish MAPL function as a regulator of bile acid synthesis whose loss leads to the disruption of bile acid feedback mechanisms. The consequences of MAPL loss in liver, along with evidence of tumor suppression through regulation of cell survival pathways, ultimately lead to hepatocellular carcinogenesis.
Topics: Animals; Mice; Bile; Bile Acids and Salts; Liver; Mice, Knockout; Mitochondrial Proteins; Ubiquitin-Protein Ligases; Ubiquitins
PubMed: 37962001
DOI: 10.15252/embr.202357972 -
Frontiers in Cellular and Infection... 2022Bile reflux can cause inflammation, gastric mucosa atrophy, and diseases such as stomach cancer. Alkaline bile flowing back into the stomach affects the intragastric...
BACKGROUND
Bile reflux can cause inflammation, gastric mucosa atrophy, and diseases such as stomach cancer. Alkaline bile flowing back into the stomach affects the intragastric environment and can alter the gastric bacterial community. We sought to identify the characteristics of the stomach mucosal microbiota in patients with bile reflux.
METHODS
Gastric mucosal samples were collected from 52 and 40 chronic gastritis patients with and without bile reflux, respectively. The bacterial profile was determined using 16S rRNA gene analysis.
RESULTS
In the absence of H. pylori infection, the richness (based on the Sobs and Chao1 indices; P <0.05) and diversity (based on Shannon indices; P <0.05) of gastric mucosa microbiota were higher in patients with bile reflux patients than in those without. There was a marked difference in the microbiota structure between patients with and without bile reflux (ANOSIM, R=0.058, P=0.011). While the genera, , , , , , , and were enriched in patients with bile reflux, the genera, , , and , were enriched in those without bile reflux.
CONCLUSION
Our results demonstrate that bile reflux significantly alters the composition of the gastric microbiota.
Topics: Bile Reflux; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Microbiota; RNA, Ribosomal, 16S
PubMed: 36159635
DOI: 10.3389/fcimb.2022.940687 -
Annals of Gastroenterological Surgery Jan 2020Isolated bile leakage (IBL) after hepatectomy is intractable, and various treatment methods for it have been reported. This review aimed to clarify the treatment... (Review)
Review
Isolated bile leakage (IBL) after hepatectomy is intractable, and various treatment methods for it have been reported. This review aimed to clarify the treatment strategy for IBL by summarizing studies on IBL after hepatectomy without extrahepatic bile duct resection. Thirty-three cases of IBL were reported. The incidence of IBL is very low, accounting for 0.1%-1% of all hepatectomy cases. The risk factors for IBL are unclear; however, several reports mention that biliary anomaly is associated with a high risk of IBL, with preoperative and intraoperative confirmation of biliary tree anatomy being the most important preventive strategy. Treatment methods for IBL include liver resection, bilioenteric anastomosis, endoscopic treatment, bile duct ablation, percutaneous transhepatic portal vein embolization (PTPE), transcatheter arterial embolization, and use of fibrin glue. The therapeutic methods should be chosen depending on remnant liver function, amount of bile leakage, and the liver volume causing the bile leakage. When there is bile leakage from less than one segment, non-surgical treatment is recommended, whereas when there is bile leakage from one or more segments, surgical treatment can be recommended. Nevertheless, recently, non-surgical treatment such as PTPE, PTPE with bile duct ablation, and endoscopic methods have been considered as effective treatment approaches.
PubMed: 32021958
DOI: 10.1002/ags3.12303 -
Journal of Clinical Medicine Dec 2021New drugs targeting bile acid metabolism are currently being evaluated in clinical studies for their potential to treat cholestatic liver diseases, non-alcoholic fatty... (Review)
Review
New drugs targeting bile acid metabolism are currently being evaluated in clinical studies for their potential to treat cholestatic liver diseases, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Changes in bile acid metabolism, however, translate into an alteration of plasma cholesterol and triglyceride concentrations, which may also affect cardiovascular outcomes in such patients. This review attempts to gain insight into this matter and improve our understanding of the interactions between bile acid and lipid metabolism. Bile acid sequestrants (BAS), which bind bile acids in the intestine and promote their faecal excretion, have long been used in the clinic to reduce LDL cholesterol and, thereby, atherosclerotic cardiovascular disease (ASCVD) risk. However, BAS modestly but consistently increase plasma triglycerides, which is considered a causal risk factor for ASCVD. Like BAS, inhibitors of the apical sodium-dependent bile acid transporter (ASBTi's) reduce intestinal bile acid absorption. ASBTi's show effects that are quite similar to those obtained with BAS, which is anticipated when considering that accelerated faecal loss of bile acids is compensated by an increased hepatic synthesis of bile acids from cholesterol. Oppositely, treatment with farnesoid X receptor agonists, resulting in inhibition of bile acid synthesis, appears to be associated with increased LDL cholesterol. In conclusion, the increasing efforts to employ drugs that intervene in bile acid metabolism and signalling pathways for the treatment of metabolic diseases such as NAFLD warrants reinforcing interactions between the bile acid and lipid and lipoprotein research fields. This review may be considered as the first step in this process.
PubMed: 35011746
DOI: 10.3390/jcm11010004