scholarly journals IMBALANCED IMMUNOBIOLOGICAL REACTIVITY, INFECTION AND MUTAGENESIS FACTORS IN THE HEPATOBILIARY SYSTEM AFFECTED BY A NATURAL FOCAL HABITAT FACTOR – A TREMATODE INVASION BY OPISTHORCHIS FELINEUS

2021 ◽  
Author(s):  
Angelina Rybka
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bacterial Species ◽  
Bile Acid Concentration ◽  
Opisthorchis Felineus ◽  
Hepatobiliary System ◽  
Study Results ◽  
Immunobiological Reactivity ◽  
Secondary Bile Acids

An interaction between decreasing host anti-infective defense due to long-term invasion with Opisthorchis felineus in the hepatobiliary system, duct bile colonization by microflora and revealing the endogenous mutagenesis (carcinogenesis) factor - secondary bile acids - in bile is considered in the article.  The role of organism genotype in the pathogen-related immune response to Opisthorchis felineus trematode and helminth development in the hepatobiliary system has been shown. The role of dysregulated mechanisms of tissue homeostasis in induction of compensatory chronic homeostatic proliferation and somatic cell oncogenesis is discussed. The study results evidence that disturbed functioning of the regulatory T-cells, inhibition of the NK cell effector function and very high functional activity of the memory B-cells are of great importance in imbalanced host immunobiological reactivity, caused by chronic opistorchosis invasion. Decreased host anti-infective protection causes intrahepatic bile duct infection with different bacterial species. Presence of secondary bile acids in hepatobiliary system was associated with biliary bacterial strains inhabiting intestinal tract: Proteus vulgaris*, Proteus mirabilis*, Citrobacter freundii*, Bacteroides alcaligues faecalis*, Clostridium*, Streptococcus faecalis*, Еscherichia coli* (*gut microflora). Participation of microbiota in bile acid biotransformation immediately in the duct bile has been confirmed in in vitro experiments. Experimental methods on Drosophila melanogaster and Salmonella tiphimurium strains: TA 100, TA 98 allowed to find out that bile from chronic opistorchosis patients exerts higher mutagenic activity compared with control groups. Mutational events in somatic and bacterial cells depend on the presence of secondary bile acids (deoxycholic, lithocholic) in duct bile, as well as the level of total bile acid concentration. The study data confirm the concept by Professor A.A. Shain about presence of endogenous risk factor for developing primary cholangiocellular liver cancer such as secondary bile acids in the bile of chronic opistorchosis patients. A concept of cholangiocarcinogenesis, based on mutational events, is added up with disturbance of generative cycle in tissue cells and their differentiation due to decreased kylon factor activity, as well as sensitivity threshold to it. Level of investigation and understanding of mechanisms underlying cholangiocarcinogenesis during chronic opisthorchiasis invasion will allow to develop pathogenetic approaches to correct homeostasis regulation and prevention of cholangiocarcinomas.

The role of secondary bile acids in neoplastic development in the oesophagus

2010 ◽  
Vol 38 (2) ◽  
pp. 337-342 ◽  
Author(s):  
James Cronin ◽  
Lisa Williams ◽  
Elizabeth McAdam ◽  
Zak Eltahir ◽  
Paul Griffiths ◽  
...  
Keyword(s):  
Dna Damage ◽  
Bile Acid ◽  
Bile Acids ◽  
Association Studies ◽  
Nuclear Factor Κb ◽  
Dna Damaging Agents ◽  
Pkc Protein Kinase C ◽  
Oxide Synthase ◽  
Secondary Bile Acids

Bile acids have been demonstrated, through the use of animal models and clinical association studies, to play a role in neoplastic development in Barrett's metaplasia. How specific bile acids promote neoplasia is as yet unknown, as are the exact identities of the important bile acid subtypes. The combination of bile subtype with appropriate pH is critical, as pH alters bile acid activity enormously. Hence glycine-conjugated bile acids are involved in neoplastic development at acidic pH (pH ~4), and unconjugated bile acids are involved in neoplastic development at more neutral pH (~6). Bile acids (at the appropriate pH) are potent DNA-damaging agents, due to the induction of ROS (reactive oxygen species), which are mainly induced by bile-induced damage to mitochondrial membranes, allowing leakage of ROS into the cytosol. These ROS also induce pro-survival signalling pathways [e.g. via PKC (protein kinase C)-dependent NF-κB (nuclear factor κB) activity]. Interestingly, NOS (nitric oxide synthase), through induction of NO may exacerbate this NF-κB activity and form a positive-feedback loop to amplify the activation of NF-κB by deoxycholic acid in particular. This combination of induced DNA damage and cell survival by bile acids is of major importance in neoplasia. Antioxidants and the tertiary bile acid UDCA (ursodeoxycholic acid) can block bile-induced DNA damage and bile-induced NF-κB activity, and should be considered in chemopreventative strategies.

scholarly journals Bile Acid 7α-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids

2019 ◽  
Vol 26 (1) ◽  
pp. 27-34.e4 ◽  
Author(s):  
Jason D. Kang ◽  
Christopher J. Myers ◽  
Spencer C. Harris ◽  
Genta Kakiyama ◽  
In-Kyoung Lee ◽  
...  
Keyword(s):  
Bile Acid ◽  
Clostridium Difficile ◽  
Bile Acids ◽  
Gut Bacteria ◽  
Secondary Bile Acids

scholarly journals Comparative Genomic and Physiological Analysis against Clostridium scindens Reveals Eubacterium sp. c-25 as an Atypical Deoxycholic Acid Producer of the Human Gut Microbiota

2021 ◽  
Vol 9 (11) ◽  
pp. 2254
Author(s):  
Isaiah Song ◽  
Yasuhiro Gotoh ◽  
Yoshitoshi Ogura ◽  
Tetsuya Hayashi ◽  
Satoru Fukiya ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Deoxycholic Acid ◽  
Bacterial Species ◽  
Cluster Structure ◽  
Comparative Genomic ◽  
Human Gut ◽  
Physiological Analysis ◽  
Acid Substrate ◽  
Secondary Bile Acids

The human gut houses bile acid 7α-dehydroxylating bacteria that produce secondary bile acids such as deoxycholic acid (DCA) from host-derived bile acids through enzymes encoded by the bai operon. While recent metagenomic studies suggest that these bacteria are highly diverse and abundant, very few DCA producers have been identified. Here, we investigated the physiology and determined the complete genome sequence of Eubacterium sp. c-25, a DCA producer that was isolated from human feces in the 1980s. Culture experiments showed a preference for neutral to slightly alkaline pH in both growth and DCA production. Genomic analyses revealed that c-25 is phylogenetically distinct from known DCA producers and possesses a multi-cluster arrangement of predicted bile-acid inducible (bai) genes that is considerably different from the typical bai operon structure. This arrangement is also found in other intestinal bacterial species, possibly indicative of unconfirmed 7α-dehydroxylation capabilities. Functionality of the predicted bai genes was supported by the induced expression of baiB, baiCD, and baiH in the presence of cholic acid substrate. Taken together, Eubacterium sp. c-25 is an atypical DCA producer with a novel bai gene cluster structure that may represent an unexplored genotype of DCA producers in the human gut.

scholarly journals Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1104
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Richard L. Young ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Peptide Yy ◽  
Glycogen Synthesis ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Farnesoid X Receptor ◽  
Gastrointestinal Hormone ◽  
Bile Acid Sequestrants

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

Effects of Bile Salt Deconjugation by Probiotic Strains on the Survival of Antibiotic-Resistant Foodborne Pathogens under Simulated Gastric Conditions

2012 ◽  
Vol 75 (6) ◽  
pp. 1090-1098 ◽  
Author(s):  
XINLONG HE ◽  
YUNYUN ZOU ◽  
YOUNGJAE CHO ◽  
JUHEE AHN
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Foodborne Pathogens ◽  
Antibiotic Susceptibility ◽  
High Performance ◽  
Bifidobacterium Longum ◽  
Lactobacillus Rhamnosus ◽  
Antibiotic Resistant ◽  
Study Results ◽  
Probiotic Strains

This study was designed to evaluate the effects of bile acid deconjugation by probiotic strains on the antibiotic susceptibility of antibiotic-sensitive and multiple antibiotic–resistant Salmonella Typhimurium and Staphylococcus aureus. Eight probiotic strains, Bifidobacterium longum B6, Lactobacillus acidophilus ADH, Lactobacillus brevis KACC 10553, Lactobacillus casei KACC 12413, Lactobacillus paracasei ATCC 25598, Lactobacillus rhamnosus GG, Leuconostoc mesenteroides KACC 12312, and Pediococcus acidilactici KACC 12307, were used to examine bile acid tolerance. The ability to deconjugate bile acids was evaluated using both thin-layer chromatography and high-performance liquid chromatography. The antibiotic susceptibility testing was carried out to determine the synergistic inhibitory activity of deconjugated bile acids. L. acidophilus, L. brevis, and P. acidilactici showed the most tolerance to the conjugated bile acids. P. acidilactici deconjugated glycocholic acid and glycodeoxycholate from 3.18 and 3.09 mM to the detection limits, respectively. The antibiotic susceptibility of selected foodborne pathogens was increased by increasing the concentration of deconjugated bile acids. The study results are useful for understanding the relationship between bile acid deconjugation by probiotic strains and antibiotic susceptibility in the presence of deconjugated bile acids, and they may be useful for designing new probiotic-antibiotic combination therapy based on bile acid deconjugation.

scholarly journals Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiake Yu ◽  
Hu Zhang ◽  
Liya Chen ◽  
Yufei Ruan ◽  
Yiping Chen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Healthy Children ◽  
Nonalcoholic Fatty Liver ◽  
Secondary Bile Acids

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.

scholarly journals Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Bile Acid Receptors

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

TGR5 signaling mitigates parenteral nutrition-associated liver disease

2020 ◽  
Vol 318 (2) ◽  
pp. G322-G335
Author(s):  
Kent A. Willis ◽  
Charles K. Gomes ◽  
Prahlad Rao ◽  
Dejan Micic ◽  
E. Richard Moran ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Parenteral Nutrition ◽  
Bile Acids ◽  
G Protein ◽  
Prolonged Exposure ◽  
Serum Bile Acid ◽  
Immune Functions ◽  
Protein Receptor ◽  
Secondary Bile Acids

Bile acid receptors regulate the metabolic and immune functions of circulating enterohepatic bile acids. This process is disrupted by administration of parenteral nutrition (PN), which may induce progressive hepatic injury for unclear reasons, especially in the newborn, leading to PN-associated liver disease. To explore the role of bile acid signaling on neonatal hepatic function, we initially observed that Takeda G protein receptor 5 (TGR5)-specific bile acids were negatively correlated with worsening clinical disease markers in the plasma of human newborns with prolonged PN exposure. To test our resulting hypothesis that TGR5 regulates critical liver functions to PN exposure, we used TGR5 receptor deficient mice (TGR5−/−). We observed PN significantly increased liver weight, cholestasis, and serum hepatic stress enzymes in TGR5−/− mice compared with controls. Mechanistically, PN reduced bile acid synthesis genes in TGR5−/−. Serum bile acid composition revealed that PN increased unconjugated primary bile acids and secondary bile acids in TGR5−/− mice, while increasing conjugated primary bile acid levels in TGR5-competent mice. Simultaneously, PN elevated hepatic IL-6 expression and infiltrating macrophages in TGR5−/− mice. However, the gut microbiota of TGR5−/− mice compared with WT mice following PN administration displayed highly elevated levels of Bacteroides and Parabacteroides, and possibly responsible for the elevated levels of secondary bile acids in TGR5−/− animals. Intestinal bile acid transporters expression was unchanged. Collectively, this suggests TGR5 signaling specifically regulates fundamental aspects of liver bile acid homeostasis during exposure to PN. Loss of TGR5 is associated with biochemical evidence of cholestasis in both humans and mice on PN. NEW & NOTEWORTHY Parenteral nutrition is associated with deleterious metabolic outcomes in patients with prolonged exposure. Here, we demonstrate that accelerated cholestasis and parental nutrition-associated liver disease (PNALD) may be associated with deficiency of Takeda G protein receptor 5 (TGR5) signaling. The microbiome is responsible for production of secondary bile acids that signal through TGR5. Therefore, collectively, these data support the hypothesis that a lack of established microbiome in early life or under prolonged parenteral nutrition may underpin disease development and PNALD.

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