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The Korean Journal of Gastroenterology... Apr 2024Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD... (Review)
Review
Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD patients, a portion of bile from the small intestine that is normally controlled by enterohepatic circulation is present at a high concentration in the lumen of the large intestine, resulting in increased motility and secretion of the large intestine. The prevalence of BAD is estimated to be 1-2% of the general population, and it comprises one-third of the instances of diarrhea-predominant irritable bowel syndrome. The clinical symptoms of BAD include chronic diarrhea, increased frequency of defecation, urgency to defecate, fecal incontinence, and cramping abdominal pain. The pathophysiology of BAD has not yet been fully elucidated. However, recent studies have reported increased intestinal permeability, shortened intestinal transit time, and changes in the intestinal microbial community to be the possible causes of BAD. Although fecal and serum bile acid tests are widely used for diagnosis, new test methods that are non-invasive, inexpensive, and have high sensitivity and specificity are needed at various institutions to facilitate the diagnosis. The selenium homo-tauro-cholic acid (SeHCAT) test is the gold standard for BAD diagnosis and severity assessment. The validation of several other serum markers, such as 7-hydroxy-4-cholesten-3-one (serum 7αC4) and the fibroblast growth factor 19 (FGF19) for use in clinical practice is ongoing. Although bile acid sequestrants are the mainstay of treatment, the development of drugs that are more effective and have better compliance is required. Farnesoid X receptor (FXR) agonists are showing promising results.
Topics: Humans; Diarrhea; Bile Acids and Salts
PubMed: 38659249
DOI: 10.4166/kjg.2023.119 -
Cells Jul 2023The intestinal barrier is a precisely regulated semi-permeable physiological structure that absorbs nutrients and protects the internal environment from infiltration of... (Review)
Review
The intestinal barrier is a precisely regulated semi-permeable physiological structure that absorbs nutrients and protects the internal environment from infiltration of pathological molecules and microorganisms. Bile acids are small molecules synthesized from cholesterol in the liver, secreted into the duodenum, and transformed to secondary or tertiary bile acids by the gut microbiota. Bile acids interact with bile acid receptors (BARs) or gut microbiota, which plays a key role in maintaining the homeostasis of the intestinal barrier. In this review, we summarize and discuss the recent studies on bile acid disorder associated with intestinal barrier dysfunction and related diseases. We focus on the roles of bile acids, BARs, and gut microbiota in triggering intestinal barrier dysfunction. Insights for the future prevention and treatment of intestinal barrier dysfunction and related diseases are provided.
Topics: Humans; Bile Acids and Salts; Intestines; Gastrointestinal Diseases; Liver; Gastrointestinal Microbiome
PubMed: 37508557
DOI: 10.3390/cells12141888 -
Cell Proliferation Dec 2023Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains...
Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains unclear, however. The data of ICC and healthy individuals were downloaded from the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases. Meanwhile, a cutting-edge ICC high-resolution spatial transcriptome was also acquired before these data were comprehensively analysed using bioinformatics approaches. Moreover, 95 individuals with ICC who had undergone resection surgery were enrolled in this study to investigate the relationship between HEV and tumour microenvironment (TME) applying immunohistochemistry and multiple immunofluorescence techniques. The high-HEV subtype contains rich immune infiltrates including tertiary lymphoid structure (TLS), CD8+ T cells, and CD20+ B cells. Furthermore, HEV and TLS exhibited a strong relationship of spatial colocalization. Correlated with improved prognostic outcomes in ICC, the high-HEV subtype could be an independent prognostic indicator for individuals with ICC. This study revealed the association of HEV with immune function and observed a strong spatial colocalization correlation between HEV and TLS. Moreover, correlated with immunotherapeutic response, HEV could improve prognostic outcomes, which may be a potential indicator of immunotherapy pathology in ICC.
Topics: Humans; Prognosis; Venules; Cholangiocarcinoma; Biomarkers; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Tumor Microenvironment
PubMed: 37401015
DOI: 10.1111/cpr.13513 -
Toxicologic Pathology Oct 2023Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure.... (Review)
Review
Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure. One mechanism of DILI is altered bile acid homeostasis and involves several hepatic bile acid transporters. Functional impairment of some hepatic bile acid transporters by drugs, disease, or genetic mutations may lead to toxic accumulation of bile acids within hepatocytes and increase DILI susceptibility. This review focuses on the role of hepatic bile acid transporters in DILI. Model systems, primarily and modeling tools, such as DILIsym, used in assessing transporter-mediated DILI are discussed. Due to species differences in bile acid homeostasis and drug-transporter interactions, key aspects and challenges associated with the use of preclinical animal models for DILI assessment are emphasized. Learnings are highlighted from three case studies of hepatotoxic drugs: troglitazone, tolvaptan, and tyrosine kinase inhibitors (dasatinib, pazopanib, and sorafenib). The development of advanced models and novel biomarkers that can reliably predict DILI is critical and remains an important focus of ongoing investigations to minimize patient risk for liver-related adverse reactions associated with medication use.
Topics: Animals; Humans; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Bile Acids and Salts; Carrier Proteins; Membrane Glycoproteins
PubMed: 37982363
DOI: 10.1177/01926233231212255 -
Cancers Jul 2023Evidence suggests the involvement of the microbiota, including oral, intra-tumoral and gut, in pancreatic cancer progression and response to therapy. The gut microbiota... (Review)
Review
Evidence suggests the involvement of the microbiota, including oral, intra-tumoral and gut, in pancreatic cancer progression and response to therapy. The gut microbiota modulates the bile acid pool and is associated with maintaining host physiology. Studies have shown that the bile acid/gut microbiota axis is dysregulated in pancreatic cancer. Bile acid receptor expression and bile acid levels are dysregulated in pancreatic cancer as well. Studies have also shown that bile acids can cause pancreatic cell injury and facilitate cancer cell proliferation. The microbiota and its metabolites, including bile acids, are also altered in other conditions considered risk factors for pancreatic cancer development and can alter responses to chemotherapeutic treatments, thus affecting patient outcomes. Altogether, these findings suggest that the gut microbial and/or bile acid profiles could also serve as biomarkers for pancreatic cancer detection. This review will discuss the current knowledge on the interaction between gut microbiota interaction and bile acid metabolism in pancreatic cancer.
PubMed: 37509236
DOI: 10.3390/cancers15143573 -
Clinica Chimica Acta; International... Nov 2023Biliary tract cancers are heterogeneous in etiology, morphology and molecular characteristics thus impacting disease management. Diagnosis is complex and prognosis poor.... (Review)
Review
Biliary tract cancers are heterogeneous in etiology, morphology and molecular characteristics thus impacting disease management. Diagnosis is complex and prognosis poor. The advent of liquid biopsy has provided a unique approach to more thoroughly understand tumor biology in general and biliary tract cancers specifically. Due to their minimally invasive nature, liquid biopsy can be used to serially monitor disease progression and allow real-time monitoring of tumor genetic profiles as well as therapeutic response. Due to the unique anatomic location of biliary tract cancer, bile provides a promising biologic fluid for this purpose. This review focuses on the composition of bile and the use of these various components, ie, cells, extracellular vesicles, nucleic acids, proteins and metabolites as potential biomarkers. Based on the disease characteristics and research status of biliary tract cancer, considerable effort should be made to increase understanding of this disease, promote research and development into early diagnosis, develop efficient diagnostic, therapeutic and prognostic markers.
Topics: Humans; Bile; Biomarkers, Tumor; Biliary Tract Neoplasms; Prognosis; Liquid Biopsy
PubMed: 37839517
DOI: 10.1016/j.cca.2023.117593 -
Biomedicine & Pharmacotherapy =... Oct 2023Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct epithelial cells, is characterized by aggressiveness, difficult diagnosis, and poor prognosis due to... (Review)
Review
Cholangiocarcinoma (CCA), a heterogeneous malignancy of bile duct epithelial cells, is characterized by aggressiveness, difficult diagnosis, and poor prognosis due to limited understanding and lack of effective therapeutic strategies. Genetic and epigenetic alterations accumulated in CCA cells can cause the aberrant regulation of oncogenes and tumor suppressors. Epigenetic alterations with histone modification, DNA methylation, and noncoding RNA modulation are associated with the carcinogenesis of CCA. Mutation or silencing of genes by various mechanisms can be a frequent event during CCA development. Alterations in histone acetylation/deacetylation at the posttranslational level, DNA methylation at promoters, and noncoding RNA regulation contribute to the heterogeneity of CCA and drive tumor development. In this review article, we mainly focus on the roles of epigenetic regulation in cholangiocarcinogenesis. Alterations in epigenetic modification can be potential targets for the therapeutic management of CCA, and epigenetic targets may become diagnostic biomarkers of CCA.
Topics: Humans; Epigenesis, Genetic; Bile Duct Neoplasms; Cholangiocarcinoma; Bile Ducts; Bile Ducts, Intrahepatic
PubMed: 37557012
DOI: 10.1016/j.biopha.2023.115290