-
Cellular and Molecular Life Sciences :... Apr 2022Bile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array of metabolites. The... (Review)
Review
Bile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array of metabolites. The bulk of bile acid synthesis takes place in the liver yielding primary bile acids; however, other tissues have also the capacity to generate bile acids (e.g. ovaries). Hepatic bile acids are then transported to bile and are subsequently released into the intestines. In the large intestine, a fraction of primary bile acids is converted to secondary bile acids by gut bacteria. The majority of the intestinal bile acids undergo reuptake and return to the liver. A small fraction of secondary and primary bile acids remains in the circulation and exert receptor-mediated and pure chemical effects (e.g. acidic bile in oesophageal cancer) on cancer cells. In this review, we assess how changes to bile acid biosynthesis, bile acid flux and local bile acid concentration modulate the behavior of different cancers. Here, we present in-depth the involvement of bile acids in oesophageal, gastric, hepatocellular, pancreatic, colorectal, breast, prostate, ovarian cancer. Previous studies often used bile acids in supraphysiological concentration, sometimes in concentrations 1000 times higher than the highest reported tissue or serum concentrations likely eliciting unspecific effects, a practice that we advocate against in this review. Furthermore, we show that, although bile acids were classically considered as pro-carcinogenic agents (e.g. oesophageal cancer), the dogma that switch, as lower concentrations of bile acids that correspond to their serum or tissue reference concentration possess anticancer activity in a subset of cancers. Differences in the response of cancers to bile acids lie in the differential expression of bile acid receptors between cancers (e.g. FXR vs. TGR5). UDCA, a bile acid that is sold as a generic medication against cholestasis or biliary surge, and its conjugates were identified with almost purely anticancer features suggesting a possibility for drug repurposing. Taken together, bile acids were considered as tumor inducers or tumor promoter molecules; nevertheless, in certain cancers, like breast cancer, bile acids in their reference concentrations may act as tumor suppressors suggesting a Janus-faced nature of bile acids in carcinogenesis.
Topics: Bile Acids and Salts; Carcinogenesis; Esophageal Neoplasms; Humans; Liver; Male
PubMed: 35429253
DOI: 10.1007/s00018-022-04278-2 -
Cell Metabolism Aug 2021FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR...
FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono- and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
Topics: Animals; Bile; Bile Acids and Salts; Humans; Lipids; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phosphatidate Phosphatase; Receptors, Cytoplasmic and Nuclear
PubMed: 34270928
DOI: 10.1016/j.cmet.2021.06.012 -
Nutrients Jan 2022The objective of the present research was to review the state of the art on the consequences of drinking coffee at the different levels of the gastrointestinal tract. At... (Review)
Review
The objective of the present research was to review the state of the art on the consequences of drinking coffee at the different levels of the gastrointestinal tract. At some steps of the digestive process, the effects of coffee consumption seem rather clear. This is the case for the stimulation of gastric acid secretion, the stimulation of biliary and pancreatic secretion, the reduction of gallstone risk, the stimulation of colic motility, and changes in the composition of gut microbiota. Other aspects are still controversial, such as the possibility for coffee to affect gastro-esophageal reflux, peptic ulcers, and intestinal inflammatory diseases. This review also includes a brief summary on the lack of association between coffee consumption and cancer of the different digestive organs, and points to the powerful protective effect of coffee against the risk of hepatocellular carcinoma. This review reports the available evidence on different topics and identifies the areas that would most benefit from additional studies.
Topics: Bile; Caffeine; Coffee; Female; Gallstones; Gastric Acid; Gastroesophageal Reflux; Gastrointestinal Microbiome; Gastrointestinal Motility; Gastrointestinal Neoplasms; Gastrointestinal Tract; Humans; Inflammatory Bowel Diseases; Male; Pancreas; Peptic Ulcer; Saliva
PubMed: 35057580
DOI: 10.3390/nu14020399 -
Gut Microbes 2020Bile acid biotransformation is a collaborative effort by the host and the gut microbiome. Host hepatocytes synthesize primary bile acids from cholesterol. Once these... (Review)
Review
Bile acid biotransformation is a collaborative effort by the host and the gut microbiome. Host hepatocytes synthesize primary bile acids from cholesterol. Once these host-derived primary bile acids enter the gastrointestinal tract, the gut microbiota chemically modify them into secondary bile acids. Interest into the gut-bile acid-host axis is expanding in diverse fields including gastroenterology, endocrinology, oncology, and infectious disease. This review aims to 1) describe the physiologic aspects of collaborative bile acid metabolism by the host and gut microbiota; 2) to evaluate how gut microbes influence bile acid pools, and in turn how bile acid pools modulate the gut microbial community structure; 3) to compare species differences in bile acid pools; and lastly, 4) discuss the effects of ursodeoxycholic acid (UDCA) administration, a common therapeutic bile acid, on the gut microbiota-bile acid-host axis.
Topics: Animals; Bacteria; Bile Acids and Salts; Cholesterol; Clostridioides difficile; Gastrointestinal Microbiome; Hepatocytes; Humans; Lipid Metabolism; Microbiota; Receptors, Cytoplasmic and Nuclear; Ursodeoxycholic Acid
PubMed: 31595814
DOI: 10.1080/19490976.2019.1674124 -
Nutrients Sep 2021Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum (including bacteria involved in bile acid metabolism) and the enrichment of phylum . Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.
Topics: Animals; Bile Acids and Salts; Gastrointestinal Microbiome; Humans; Inflammatory Bowel Diseases
PubMed: 34579027
DOI: 10.3390/nu13093143 -
Biomolecules Apr 2022Gallstone disease is a common pathology of the digestive system with nearly a 10-20% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is... (Review)
Review
Gallstone disease is a common pathology of the digestive system with nearly a 10-20% incidence rate among adults. The mainstay of treatment is cholecystectomy, which is commonly associated with physical pain and may also seriously affect a patient's quality of life. Clinical research suggests that cholelithiasis is closely related to the age, gender, body mass index, and other basic physical characteristics of patients. Clinical research further suggests that the occurrence of cholelithiasis is related to obesity, diabetes, non-alcoholic fatty liver, and other diseases. For this reason, we reviewed the following: genetic factors; excessive liver cholesterol secretion (causing cholesterol supersaturation in gallbladder bile); accelerated growth of cholesterol crystals and solid cholesterol crystals; gallbladder motility impairment; and cardiovascular factors. Herein, we summarize and analyze the causes and mechanisms of cholelithiasis, discuss its correlation with the pathogenesis of related diseases, and discuss possible mechanisms.
Topics: Adult; Bile; Bile Acids and Salts; Cholesterol; Gallstones; Humans; Quality of Life
PubMed: 35454138
DOI: 10.3390/biom12040550 -
Nature Communications Jan 2022Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the...
Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, HS increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.
Topics: Animals; Bile; Bile Acids and Salts; Cholelithiasis; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Desulfovibrionales; Digestion; Feces; Gallstones; Gastrointestinal Microbiome; Intestinal Absorption; Lipid Metabolism; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Microbiota
PubMed: 35017486
DOI: 10.1038/s41467-021-27758-8 -
World Journal of Gastroenterology Mar 2023Cholelithiasis is a common digestive disease affecting 10% to 15% of adults. It imposes significant global health and financial burdens. However, the pathogenesis of... (Review)
Review
Cholelithiasis is a common digestive disease affecting 10% to 15% of adults. It imposes significant global health and financial burdens. However, the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated. In addition to genetic predisposition and hepatic hypersecretion, the pathogenesis of cholelithiasis might involve the gastrointestinal (GI) microbiome, consisting of microorganisms and their metabolites. High-throughput sequencing studies have elucidated the role of bile, gallstones, and the fecal microbiome in cholelithiasis, associating microbiota dysbiosis with gallstone formation. The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways. This review examines the literature implicating the GI microbiome in cholelithiasis, specifically gallbladder stones, choledocholithiasis, and asymptomatic gallstones. We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.
Topics: Gastrointestinal Microbiome; Humans; Choledocholithiasis; Bile Acids and Salts; Liver
PubMed: 36970590
DOI: 10.3748/wjg.v29.i10.1589