Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.
Bacterial Infections/physiopathology* ; Bile Acids and Salts/physiology* ; Cholestasis/physiopathology* ; Enteral Nutrition ; Gastrointestinal Microbiome/physiology* ; Humans ; Intestinal Diseases/physiopathology* ; Intestines/physiopathology* ; Liver/physiopathology* ; Liver Diseases/physiopathology* ; Parenteral Nutrition/adverse effects* ; Short Bowel Syndrome/physiopathology* ; Signal Transduction

BACKGROUND/AIMS: Cholangiocytes are capable of reabsorbing bile salts from bile, but the pathophysiological significance of this process is unclear. To this end, we detected the expression and distribution of bile acid transport proteins in cholangiocytes from normal rat liver and analyzed the possible pathophysiological significance. METHODS: Bile duct tissues of Sprague-Dawley rats were isolated by enzymatic digestion and mechanical isolation, and then divided into large and small bile duct tissues. Immunohistochemistry, real-time polymerase chain reaction and Western blotting were used to determine the expression of the apical sodium-dependent bile acid transporter (ASBT), ileal bile acid binding protein (IBABP), and basolateral organic solute transporter α (Ostα) in the biliary tract system of rats. Differences in the expression and distribution of these proteins were analyzed. RESULTS: In cholangiocytes, ASBT and IBABP were mainly expressed in cholangiocytes of the large bile ducts, in which the expression of both was significantly higher than that in the small ducts (p<0.05). Ostα was simultaneously expressed in cholangiocytes of both the large and small bile ducts, showing no significant difference in expression between the two groups of bile ducts (p>0.05). CONCLUSIONS: Bile acid transporters are expressed and heterogeneously distributed in rat bile ducts, indicating that bile acid reabsorption by cholangiocytes might mainly occur in the large bile ducts. These findings may help explore the physiology of bile ducts and the pathogenesis of various cholangiopathies.
Animals ; Bile Acids and Salts ; Bile Ducts ; Bile ; Biliary Tract ; Blotting, Western ; Carrier Proteins ; Digestion ; Immunohistochemistry ; Liver ; Physiology ; Population Characteristics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

Over the past decade, there has been increasing attention on the interaction between microbiota and bile acid metabolism. Bile acids are not only involved in the metabolism of nutrients, but are also important in signal transduction for the regulation of host physiological activities. Microbial-regulated bile acid metabolism has been proven to affect many diseases, but there have not been many studies of disease regulation by microbial receptor signaling pathways. This review considers findings of recent research on the core roles of farnesoid X receptor (FXR), G protein-coupled bile acid receptor (TGR5), and vitamin D receptor (VDR) signaling pathways in microbial-host interactions in health and disease. Studying the relationship between these pathways can help us understand the pathogenesis of human diseases, and lead to new solutions for their treatments.
Bile Acids and Salts/metabolism* ; Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism* ; Metabolic Syndrome/metabolism* ; Receptors, Calcitriol/physiology* ; Receptors, Cytoplasmic and Nuclear/physiology* ; Receptors, G-Protein-Coupled/physiology* ; Signal Transduction/physiology*

Excess energy intake, without a compensatory increase of energy expenditure, leads to obesity. Several molecules are involved in energy homeostasis regulation and new ones are being discovered constantly. Appetite regulating hormones such as ghrelin, peptide tyrosine-tyrosine and amylin or incretins such as the gastric inhibitory polypeptide have been studied extensively while other molecules such as fibroblast growth factor 21, chemerin, irisin, secreted frizzle-related protein-4, total bile acids, and heme oxygenase-1 have been linked to energy homeostasis regulation more recently and the specific role of each one of them has not been fully elucidated. This mini review focuses on the above mentioned molecules and discusses them in relation to their regulation by the macronutrient composition of the diet as well as diet-induced weight loss.
Appetite ; Bile Acids and Salts ; Diet ; Energy Intake ; Energy Metabolism ; Fibroblast Growth Factors ; Gastric Inhibitory Polypeptide ; Ghrelin ; Heme Oxygenase-1 ; Homeostasis* ; Incretins ; Islet Amyloid Polypeptide ; Obesity ; Physiology* ; Weight Loss*

Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn's disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD.
Anticholesteremic Agents/therapeutic use ; Bile Acids and Salts/*physiology ; Crohn Disease/complications ; Diarrhea/*etiology/pathology/therapy ; Feces/chemistry ; Fibroblast Growth Factors/deficiency ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/complications

Animals ; Autocrine Communication ; physiology ; Bile Acids and Salts ; metabolism ; Carbohydrate Metabolism ; Exocrine Glands ; physiology ; Fibroblast Growth Factors ; physiology ; Homeostasis ; physiology ; Humans ; Lipid Metabolism ; Metabolic Diseases ; metabolism

Bile acid is a type of metabolite degraded from cholesterol in liver. Its accumulation in liver could cause liver diseases, liver damage and liver fibrosis. In this experiment, dimethyl nitrosamine (DMN) liver fibrosis was established in rats. The rats were delivered into the normal group, the model group and four treated groups. After the four-week modeling, the treated groups were orally administered with drugs for 2 weeks, whereas the model and normal groups were given equal amount of sterile water at the same time. In the experiment, serum bile acid was taken the as marker, and liver function indexes and changes in bile acid metabolism were detected and observed to identify liver damage-related bile acid targets. It was the first time to evaluate the reverse effect of artificial CsB and its components on liver fibrosis in rats with bile acid metabolic level, and discuss its potential mechanism. The main study contents and results are as follows: a quantitative analysis was made on totally 17 endogenous bile acids, including taurocholic acid conjugated bile acid, glycine conjugated bile acid and free bile acid, and a liver damage evaluation was made for the model according to the detection of serum biochemical indexes and the pathological biopsy. After modeling, ALT, AST activity and TBil content significantly increased, whereas Alb significantly decreased. According to the pathological biopsy HE staining, the model group showed damage in normal hepatic lobule structure, liver cell edema and connective tissue proliferation in portal area; The treated groups showed mitigation in pathological changes to varying degrees. Cordyceps sinensis and its components may impact the bile acid metabolism in rats by activating HDCA, TCA, TCDCA, TLCA, TUDCA, UDCA, THDCA metabolim-related receptors or blocking relevant signaling pathway.
Animals ; Bile Acids and Salts ; metabolism ; Biological Factors ; administration & dosage ; Cordyceps ; chemistry ; physiology ; Humans ; Liver Cirrhosis ; drug therapy ; metabolism ; Male ; Moths ; chemistry ; microbiology ; Rats ; Rats, Wistar

Clonorchis sinensis is a biological carcinogen inducing human cholangiocarcinoma, and clonorchiasis is one of the important endemic infectious diseases in East Asia. The present study investigated survival longevity of C. sinensis adult worms in various in vitro conditions to find the best way of keeping the worms longer. The worms were maintained in 0.85% NaCl, 1xPBS, 1xLocke's solution, RPMI-1640, DMEM, and IMDM media, and in 1xLocke's solution with different supplements. All of the worms died within 3 and 7 days in 0.85% NaCl and 1xPBS, respectively, but survived up to 57 days in 1xLocke's solution. The worms lived for 106 days in DMEM, and 114 days in both RPMI-1640 and IMDM media. The survival rate in RPMI-1640 medium was the highest (50%) compared to that in DMEM (20+/-10%) and in IMDM (33.3+/-25.2%) after 3 months. The 1xLocke's solution with 0.005% bovine bile supplement showed increased duration of maximum survival from 42 days to 70 days. Higher concentration of bile supplements than 0.005% or addition of glucose were disadvantageous for the worm survival. The worms died rapidly in solutions containing L-aspartic acid, L-glutamic acid, and adenine compared to L-arginine, L-serine, and L-tryptophan. In conclusion, the 1xLocke's solution best supports the worms alive among inorganic solutions for 57 days, and the RPMI-1640 medium maintains living C. sinensis adults better and longer up to 114 days in vitro than other media.
Adenine/metabolism ; Amino Acids/metabolism ; Animals ; Bile/parasitology ; Bile Acids and Salts/*metabolism ; Cattle ; Cell Survival ; Clonorchiasis/*parasitology ; Clonorchis sinensis/*growth & development/physiology ; *Culture Media ; Cyprinidae ; Fish Diseases/parasitology ; Humans ; Rabbits ; Rats ; Time Factors

It was reported that pancreatic arteries constricted during the early phase of bile salt-induced acute pancreatitis (AP), leading to pancreatic microcirculatory disturbance. We conducted this experiment to verify whether the above-mentioned finding was true. AP was induced with intraductal injection of taurodeoxyholate. Small pancreatic artery pressure in dogs was recorded. Functional capillaries were counted and calibrated by multiplying wet weight of pancreas. Pancreatic perfusion was measured with Laser Doppler flowmeter. Pancreatic arterioles of rats dilated during the initial 20 min of AP, and pancreatic arterial pressure declined during the early phase of AP in dogs (from 104.5 +/- 4.8 mmHg to 54.6 +/- 5.6 mmHg). The hematocrit of blood from inferior vena cava was significantly lower than that of portal vein at 5 min after pancreatitis induction. The "true" pancreatic functional capillary density increased. The early pancreatic microcirculatory disturbance coincided with a marked increase of portal vein pressure (PVP) as high as 9.18 +/- 0.78 mmHg. Reduction of PVP to baseline level was followed by a marked increase of pancreatic perfusion (by 1.4-fold). Arterial dilatation, but not constriction, occurred during the early phase of bile salt-induced AP. The pancreatic microcirculatory disturbance was due to a marked rise in PVP that greatly reduced the pressure difference in the pancreatic blood vessels and increased plasma extravasation which led. to local hemoconcentration.
Animals ; Bile Acids and Salts ; adverse effects ; Hypertension, Portal ; complications ; Male ; Microcirculation ; drug effects ; physiology ; Pancreas ; blood supply ; Pancreatitis ; etiology ; physiopathology ; Portal Pressure ; Portal Vein ; physiopathology ; Rats ; Rats, Sprague-Dawley