scholarly journals Determination of Secondary Bile Acids in the Mice Feces. Controversies on their Involvment in the Pathogenesis of Colorectal Cancer

2015 ◽  
Vol 61 (4) ◽  
pp. 287-290
Author(s):  
Saracut Claudiu ◽  
Molnar Calin ◽  
L Farczádi ◽  
L Vlase ◽  
Tero-Vescan Amelia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bile Acids ◽  
Deoxycholic Acid ◽  
Lithocholic Acid ◽  
Normal Diet ◽  
Knowing That ◽  
Daily Ingestion ◽  
Dose Dependent ◽  
Secondary Bile Acids

AbstractObjectives: The aim of the study was to determine the level of secondary bile acids (SBA) in the diets and feces of mice and the variation of amount ingested/excreted if these SBA are administered as monotherapy or in 1:1 dose.Methods: The mice were divided into 4 groups and fed for 140 days with different diets. The control lot received a normal diet and the others received diets supplemented with 0.25% deoxycholic acid (DCA), 0.25% lithocholic acid (LCA) and 0.125% DCA+0.125% LCA. After 140 days, the mice feces were collected and homogenized to obtain a mixture for each lot from which the determinations of the studied SBA were performed. For the mice food evaluation, portions of 10 g from each of the 4 diets were subjected to the SBA determination.Results: The daily ingestion over more than 4 months of DCA or LCA added to the diet and administered as monotherapy determine a significantly increase of the SBA eliminated into the feces (the DCA level was 11x higher, and of the LCA 233x higher). If half of the LCA dose is replaced with DCA, the level of LCA in the feces gets comparable with that of the DCA (their combined amounts represents only 13x higher increase of these two bile acids in feces).Conclusions: The simultaneous ingestion and excretion of DCA and LCA can be considered as a particular situation ruled by endogenous mechanisms. This behavior represents an important observation, knowing that the bile acids effects in the colorectal cancer are dose dependent.

scholarly journals Interactions of bile acids and the gut microbiota: learning from the differences inClostridium difficileinfection between children and adults

2019 ◽  
Vol 51 (6) ◽  
pp. 218-223 ◽  
Author(s):  
Sijing Cheng ◽  
Lixin Zhu ◽  
Howard S. Faden
Keyword(s):  
Clostridium Difficile ◽  
Young Child ◽  
Bile Acids ◽  
Terminal Ileum ◽  
Deoxycholic Acid ◽  
Control Mechanism ◽  
Lithocholic Acid ◽  
The Other ◽  
Spore Forming Bacteria ◽  
Secondary Bile Acids

Bile acids and microbiota differ significantly in the gut of children and adults. In the first 3 yr of life, intestinal bile consists mostly of two primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA); however, in adults, primary bile acids are transformed into the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid. This difference has a major impact on the gut microbiome, especially on anaerobic spore-forming bacteria. CA augments germination of spores in the terminal ileum. On the other hand, DCA curtails the number of germinated anaerobes entering the cecum from the terminal ileum. The control mechanism that exists in the adult cecum is absent in the young child and results in unrestrained proliferation of anaerobes, such as Clostridium difficile, in the cecum. A similar situation may develop during antibiotic therapy when an antibiotic eradicates the anaerobic population capable of converting primary bile acids into secondary bile acids.

Consumption of Some Polyphenols Reduces Fecal Deoxycholic Acid and Lithocholic Acid, the Secondary Bile Acids of Risk Factors of Colon Cancer

2009 ◽  
Vol 57 (18) ◽  
pp. 8587-8590 ◽  
Author(s):  
Yunkyung Han ◽  
Tomoaki Haraguchi ◽  
Sumie Iwanaga ◽  
Hiroyuki Tomotake ◽  
Yukako Okazaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Colon Cancer ◽  
Bile Acids ◽  
Deoxycholic Acid ◽  
Lithocholic Acid ◽  
Secondary Bile Acids

A Direct Enzymic Assay for 7α-Hydroxy Bile Acids and Their Conjugates

1973 ◽  
Vol 44 (1) ◽  
pp. 95-98 ◽  
Author(s):  
G. A. D. Haslewood ◽  
G. M. Murphy ◽  
Judith M. Richardson
Keyword(s):  
Thin Layer ◽  
Bile Acids ◽  
Thin Layer Chromatography ◽  
Biological Fluids ◽  
Hydroxysteroid Dehydrogenase ◽  
Layer Chromatography ◽  
Enzymic Assay ◽  
Bile Acids And Salts ◽  
Secondary Bile Acids

1. A 7α-hydroxysteroid dehydrogenase preparation isolated from a strain of Escherichia coli provides a specific and rapid means for the determination of 7α-hydroxy bile acids and their conjugates. 2. When used in conjunction with 3α-hydroxysteroid dehydrogenase the method enables the concentrations of primary and secondary bile acids and salts in biological fluids to be determined directly without the use of thin-layer chromatography. 3. When used with thin-layer chromatography the method allows the specific quantitative determination of chenodeoxycholic acid or its conjugates in the presence of deoxycholic acid and its derivatives.

scholarly journals 1039. Rapid Restoration of Bile Acid Compositions After Treatment with RBX2660 for Recurrent Clostridioides difficile Infection—Results from the PUNCH CD3 Phase 3 Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S610-S610
Author(s):  
Romeo Papazyan ◽  
Bryan Fuchs ◽  
Ken Blount ◽  
Carlos Gonzalez ◽  
Bill Shannon
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Deoxycholic Acid ◽  
Lithocholic Acid ◽  
Point Group ◽  
Bile Acid Metabolism ◽  
Phase 3 ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Time Point

Abstract Background Microbiota-based treatments are increasingly evaluated as a strategy to reduce recurrence of Clostridioides difficile infection (rCDI), and their proposed mechanisms include restoration of the microbiota and microbiota-mediated functions, including bile acid metabolism. RBX2660—a broad-consortium investigational live biotherapeutic—has been evaluated in >600 participants in 6 clinical trials, with consistent reduction of rCDI recurrence. Here we report that fecal bile acid compositions were significantly restored in treatment-responsive participants in PUNCH CD3—a Phase 3 randomized, double-blinded, placebo-controlled trial of RBX2660. Methods PUNCH CD3 participants received a single dose of RBX2660 or placebo between 24 to 72 hours after completing rCDI antibiotic treatment. Clinical response was the absence of CDI recurrence at eight weeks after treatment. Participants voluntarily submitted stool samples prior to blinded study treatment (baseline), 1, 4 and 8 weeks, 3 and 6 months after receiving study treatment. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 33 bile acids from all participant fecal samples received up to the 8-week time point. Mean bile acid compositions were fit to a Dirichlet multinomial distribution and compared across time points and between RBX2660- and placebo-treated participants. Results Clinically, RBX2660 demonstrated superior efficacy versus placebo (70.4% versus 58.1%). RBX2660-treated clinical responders’ bile acid compositions shifted significantly from before to after treatment. Specifically, primary bile acids predominated before treatment, whereas secondary bile acids predominated after treatment (Figure 1A). These changes trended higher among RBX2660 responders compared to placebo responders. Importantly, median levels of lithocholic acid (LCA) and deoxycholic acid (DCA) showed large, significant increases after treatment (Figure 1B). A. Bile acid compositions before (BL) and up to 8 weeks after RBX2660 treatment among treatment responders. Compositions are shown as the fraction of total bile acids classified as primary or secondary conjugated or deconjugated bile acids. B. Concentrations of lithocholic acid (LCA) and deoxycholic acid (DCA) among RBX2660 treatment responders, shown with individual samples and time point group median with interquartile ranges. Conclusion Among PUNCH CD3 clinical responders, RBX2660 significantly restored bile acids from less to more healthy compositions. These clinically correlated bile acid shifts are highly consistent with results from a prior trial of RBX2660. Disclosures Romeo Papazyan, PhD, Ferring Research Institute (Employee) Bryan Fuchs, PhD, Ferring Pharmaceuticals (Employee) Ken Blount, PhD, Rebiotix Inc., a Ferring Company (Employee)

Identification of unique bile acid-metabolizing bacteria from the microbiome of centenarians

2020 ◽  
Author(s):  
Kenya Honda ◽  
Yuko Sato ◽  
Koji Atarashi ◽  
Damian Plichta ◽  
Yasumichi Arai ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Multidrug Resistant ◽  
Bile Acid Metabolism ◽  
Critical Determinant ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
Vancomycin Resistant ◽  
Secondary Bile Acids

Abstract Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation. The gut microbiota is considered to be a critical determinant of human health and longevity. Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified Parabacteroides merdae and Odoribacteraceae strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of P. merdae to show that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and vancomycin-resistant Enterococcus faecium. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity.

scholarly journals Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases

2017 ◽  
Vol 3 (1) ◽  
pp. 00107-2016 ◽  
Author(s):  
Adil Aldhahrani ◽  
Bernard Verdon ◽  
Chris Ward ◽  
Jeffery Pearson
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Lung Disease ◽  
Bile Acids ◽  
Chenodeoxycholic Acid ◽  
Deoxycholic Acid ◽  
Lithocholic Acid ◽  
Bronchial Epithelial Cell ◽  
Epithelial Cell Line ◽  
Bronchial Epithelial

Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B).The immortalised human bronchial epithelial cell line (BEAS-2B) was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL)-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays.Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B.Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

Radioimmunoassay of bile acids in serum.

1976 ◽  
Vol 22 (5) ◽  
pp. 602-606 ◽  
Author(s):  
L M Demers ◽  
G Hepner
Keyword(s):  
Liver Disease ◽  
Liver Function ◽  
Bile Acids ◽  
Serum Antibodies ◽  
Assay Sensitivity ◽  
Standard Curve ◽  
Covalently Linked ◽  
Secondary Bile Acids ◽  
Conjugated Bile Acids

Abstract We developed four radioimmunoassay procedures for the determination of glycine-conjugated bile acids in serum. Antibodies to two primary bile acids, cholylgycine and chenodeoxycholylglycine, and to two secondary bile acids, sulfolithocholylglycine and deoxycholylglycine, were raised in rabbits after the acids were covalently linked to albumin by use of the carbodiimide reaction. Assay sensitivity for each of these bile acids is in the picomole range with the standard curve extending from 10-80 pmol. The concentration of bile acids in serum increased in various states of liver disease and its measurement appears to be an extremely sensitive indicator of liver function.

scholarly journals The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect against intestinal inflammation by inhibition of epithelial apoptosis

2020 ◽  
Vol 8 (12) ◽  
Author(s):  
Natalia K. Lajczak‐McGinley ◽  
Emanule Porru ◽  
Ciara M. Fallon ◽  
Jessica Smyth ◽  
Caitriona Curley ◽  
...  
Keyword(s):  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Intestinal Inflammation ◽  
Lithocholic Acid ◽  
Secondary Bile Acids

scholarly journals Specific Secondary Bile Acids Control Chicken Necrotic Enteritis

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1041
Author(s):  
Mohit Bansal ◽  
Tahrir Alenezi ◽  
Ying Fu ◽  
Ayidh Almansour ◽  
Hong Wang ◽  
...  
Keyword(s):  
Bile Acids ◽  
Immune Cell ◽  
Lithocholic Acid ◽  
Body Weight Gain ◽  
Economic Losses ◽  
Broiler Chicks ◽  
Necrotic Enteritis ◽  
Crypt Hyperplasia ◽  
Secondary Bile Acids

Necrotic enteritis (NE), mainly induced by the pathogens of Clostridium perfringens and coccidia, causes huge economic losses with limited intervention options in the poultry industry. This study investigated the role of specific bile acids on NE development. Day-old broiler chicks were assigned to six groups: noninfected, NE, and NE with four bile diets of 0.32% chicken bile, 0.15% commercial ox bile, 0.15% lithocholic acid (LCA), or 0.15% deoxycholic acid (DCA). The birds were infected with Eimeria maxima at day 18 and C. perfringens at day 23 and 24. The infected birds developed clinical NE signs. The NE birds suffered severe ileitis with villus blunting, crypt hyperplasia, epithelial line disintegration, and massive immune cell infiltration, while DCA and LCA prevented the ileitis histopathology. NE induced severe body weight gain (BWG) loss, while only DCA prevented NE-induced BWG loss. Notably, DCA reduced the NE-induced inflammatory response and the colonization and invasion of C. perfringens compared to NE birds. Consistently, NE reduced the total bile acids in the ileal digesta, while dietary DCA and commercial bile restored it. Together, this study showed that DCA and LCA reduced NE histopathology, suggesting that secondary bile acids, but not total bile acid levels, play an essential role in controlling the enteritis.

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