scholarly journals An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer

2014 ◽  
pp. 1673 ◽  
Author(s):  
Hani Al-Salami ◽  
Armin Mooranian ◽  
Rebecca Negrulj ◽  
Nigel Chen-Tan ◽  
Gerald Watts ◽  
...  
Keyword(s):  
Bile Acid ◽  
Deoxycholic Acid ◽  
Permeation Enhancer ◽  
Secondary Bile Acid

scholarly journals Microbial metabolite deoxycholic acid controlsClostridium perfringens-induced chicken necrotic enteritis through attenuating cyclooxygenase signaling

2018 ◽  
Author(s):  
Hong Wang ◽  
Juan D. Latorre ◽  
Mohit Bansal ◽  
Mussie Abraha ◽  
Bilal Al-Rubaye ◽  
...  
Keyword(s):  
Bile Acid ◽  
Inflammatory Response ◽  
Inflammatory Mediators ◽  
Cell Apoptosis ◽  
Deoxycholic Acid ◽  
Intestinal Inflammation ◽  
Metabolic Product ◽  
Intestinal Cell ◽  
Necrotic Enteritis ◽  
Secondary Bile Acid

AbstractClostridium perfringens-induced necrotic enteritis (NE) has reemerged as a prevalent chicken disease worldwide due to reduced usage of prophylactic antibiotics. The lack of antimicrobial alternative strategies to control NE is mainly due to limited insight into the disease pathogenesis. The aim of this study is to investigate the role of microbiota metabolic product secondary bile acid deoxycholic acid (DCA) on preventing NE.C. perfringensgrowth was inhibited by 82.8% in 50 μM DCA Tryptic Soy Broth. SequentialEimeria maximaandC. perfringenschallenges induced acute NE showed as severe intestinal inflammation and body weight (BW) loss in broiler chickens, while 1.5 g/kg DCA diet dramatically reduced the disease. At the cellular level, DCA alleviated NE-associated ileal epithelial death and reduced lamina propria cell apoptosis. Interestingly, DCA reducedC. perfringensinvasion into ileum without altering the bacterial ileal luminal colonization. Molecular analysis showed that DCA reduced inflammatory mediators ofInfγ,Litaf, andMmp9mRNA accumulation in ileal tissue. Mechanism studies revealed thatC. perfringensinduced elevated expression of inflammatory mediators ofInfγ,Litaf,Mmp9,andPtgs2(Cyclooxygenase- 2 (COX-2) gene) in chicken splenocytes. Blocking COX signaling by pharmacological inhibitor aspirin attenuated INFγ-induced inflammatory response in the splenocytes. Consistent with thein vitroassay, chickens fed 0.12 g/kg aspirin diet protected the birds against NE-induced ileal inflammation, intestinal cell apoptosis, and BW loss. In conclusion, microbial metabolic product DCA prevents NE-induced ileal inflammation and BW loss through attenuating inflammatory response. These novel findings offer new strategies againstC. perfringens-induced diseases.Significance StatementWidespread antimicrobial resistance has become a serious challenge to both agricultural and healthcare industries. Withdrawing antimicrobials without effective alternatives exacerbates chicken productivity loss at billions of dollars every year, caused by intestinal diseases, such as coccidiosis-andC. perfringens-induced necrotic enteritis. This study revealed that microbial metabolic product secondary bile acid DCA preventsC. perfringens-induced intestinal disease in chickens through modulating inflammatory COX signaling pathways. Therefore, microbiome and its downstream targets of host inflammatory responses could be used to control NE. These findings have opened new avenues for developing novel antimicrobial free alternatives to prevent or treatC. perfringens-induced diseases.

scholarly journals Prophylactic inhibition of colonization by Streptococcus pneumoniae with the secondary bile acid metabolite deoxycholic acid

2021 ◽  
Author(s):  
Jorge E. Vidal ◽  
Meagan N. Wier ◽  
Uriel Angulo-Zamudio ◽  
Erin McDevitt ◽  
Ana G Vidal ◽  
...  
Keyword(s):  
Bile Acid ◽  
Streptococcus Pneumoniae ◽  
Deoxycholic Acid ◽  
Ex Vivo ◽  
Post Inoculation ◽  
Acid Metabolite ◽  
Nasopharyngeal Colonization ◽  
Secondary Bile Acid ◽  
Human Bile

Streptococcus pneumoniae (Spn) colonizes the nasopharynx of children and the elderly but also kills millions worldwide yearly. The secondary bile acid metabolite, deoxycholic acid (DoC), affects the viability of human pathogens but also plays multiple roles in host physiology. We assessed in vitro the antimicrobial activity of DoC and investigated its potential to eradicate Spn colonization using an ex vivo model of human nasopharyngeal colonization and an in vivo mouse model of colonization. At a physiological concentration DoC (0.5 mg/ml; 1.27 mM) killed all tested Spn strains (N=48) two h post-inoculation. The ex-vivo model of nasopharyngeal colonization showed that DoC eradicated colonization by Spn strains as soon as 10 min post-exposure. The mechanism of action did not involve activation of autolysis since the autolysis-defective double mutants ΔlytAΔlytC and ΔspxBΔlctO were as susceptible to DoC as was the wild-type (WT). Oral streptococcal species (N=20), however, were not susceptible to DoC (0.5 mg/ml). Unlike trimethoprim, whose spontaneous resistance frequency (srF) for TIGR4 or EF3030 was ≥1x10-9, no spontaneous resistance was observed with DoC (srF≥1x10-12). Finally, the efficacy of DoC to eradicate Spn colonization was assessed in vivo using a topical route via intranasal (i.n.) administration and as a prophylactic treatment. Mice challenged with Spn EF3030 carried a median of 4.05x105 cfu/ml four days post-inoculation compared to 6.67x104 cfu/ml for mice treated with DoC. Mice in the prophylactic group had a ~99% reduction of the pneumococcal density (median, 2.61 x103 cfu/ml). Thus, DoC, an endogenous human bile salt, has therapeutic potential against Spn.

scholarly journals Prophylactic inhibition of colonization by Streptococcus pneumoniae with the secondary bile acid metabolite deoxycholic acid

2021 ◽  
Author(s):  
Jorge E. Vidal ◽  
Meagan N. Wier ◽  
Uriel Angulo-Zamudio ◽  
Erin McDevitt ◽  
Ana G. Jop Vidal ◽  
...  
Keyword(s):  
Bile Acid ◽  
Streptococcus Pneumoniae ◽  
Deoxycholic Acid ◽  
Therapeutic Potential ◽  
Post Inoculation ◽  
Acid Metabolite ◽  
Nasopharyngeal Colonization ◽  
Secondary Bile Acid ◽  
Human Bile

Streptococcus pneumoniae (Spn) colonizes the nasopharynx of children and the elderly but also kills millions worldwide yearly. The secondary bile acid metabolite, deoxycholic acid (DoC), affects the viability of human pathogens but also plays multiple roles in host physiology. We assessed in vitro the antimicrobial activity of DoC and investigated its potential to eradicate Spn colonization using a model of human nasopharyngeal colonization and an in vivo mouse model of colonization. At a physiological concentration DoC (0.5 mg/ml; 1.27 mM) killed all tested Spn strains (N=48) two hours post-inoculation. The model of nasopharyngeal colonization showed that DoC eradicated colonization by Spn strains as soon as 10 min post-exposure. The mechanism of action did not involve activation of autolysis since the autolysis-defective double mutants Δ lytA Δ lytC and ΔspxBΔlctO were as susceptible to DoC as was the wild-type (WT). Oral streptococcal species (N=20), however, were not susceptible to DoC (0.5 mg/ml). Unlike trimethoprim, whose spontaneous resistance frequency (srF) for TIGR4 or EF3030 was ≥1x10 −9 , no spontaneous resistance was observed with DoC (srF≥1x10- 12 ). Finally, the efficacy of DoC to eradicate Spn colonization was assessed in vivo using a topical route via intranasal (i.n.) administration and as a prophylactic treatment. Mice challenged with Spn EF3030 carried a median of 4.05x10 5 cfu/ml four days post-inoculation compared to 6.67x10 4 cfu/ml for mice treated with DoC. Mice in the prophylactic group had a ∼99% reduction of the pneumococcal density (median, 2.61 x10 3 cfu/ml). Thus, DoC, an endogenous human bile salt, has therapeutic potential against Spn.

Pharmacological effects of secondary bile acid microparticles in diabetic murine model

2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  
Keyword(s):  
Bile Acid ◽  
Blood Glucose ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Diabetes Treatment ◽  
Secondary Bile Acid ◽  
Glucose Levels ◽  
Anti Inflammatory ◽  
Antidiabetic Effects

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

scholarly journals Microbiome and PCOS: State-of-Art and Future Aspects

2021 ◽  
Vol 22 (4) ◽  
pp. 2048
Author(s):  
Pierluigi Giampaolino ◽  
Virginia Foreste ◽  
Claudia Di Filippo ◽  
Alessandra Gallo ◽  
Antonio Mercorio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bile Acid ◽  
Peptide Yy ◽  
Fecal Microbiota Transplantation ◽  
Polycystic Ovary ◽  
Current Evidence ◽  
Low Grade ◽  
Fecal Transplant ◽  
Secondary Bile Acid ◽  
First Case

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

In Vitro Metabolism of E2, G2: Novel Bile Acid-Coupling Camptothecin Analogues, in Rat Liver Microsomes

2021 ◽  
Vol 16 ◽  
Author(s):  
Xiangli Zhang ◽  
Qin Shen ◽  
Yi Wang ◽  
Leilei Zhou ◽  
Qi Weng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Phase I ◽  
Rat Liver ◽  
Deoxycholic Acid ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Rat Liver Microsomes ◽  
Camptothecin Analogues

Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues by introducing deoxycholic acid in 20-position of CPT(camptothecin) with greater anticancer activity and lower systematic toxicity in vivo. Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). Methods: Phase Ⅰ and Phase Ⅱ metabolism of E2 and G2 in rat liver microsomes were performed respectively, and the mixed incubation of phase I and phase Ⅱ metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry. Results: The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some difference. The intrinsic clearance of G2 was 174.7mL/min. mg protein, more than three times of that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations and hydrolysis) and their further glucuronidation products. Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except some difference in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).

Isolation of six novel 7-oxo- or urso-type secondary bile acid-producing bacteria from rat cecal contents

2017 ◽  
Vol 124 (5) ◽  
pp. 514-522 ◽  
Author(s):  
Sarinya Tawthep ◽  
Satoru Fukiya ◽  
Ja-Young Lee ◽  
Masahito Hagio ◽  
Yoshitoshi Ogura ◽  
...  
Keyword(s):  
Bile Acid ◽  
Secondary Bile Acid ◽  
Acid Producing Bacteria
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