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.

scholarly journals Supplementing Garlic Nanohydrogel Optimized Growth, Gastrointestinal Integrity and Economics and Ameliorated Necrotic Enteritis in Broiler Chickens Using a Clostridium perfringens Challenge Model

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2027
Author(s):  
Doaa Ibrahim ◽  
Tamer Ahmed Ismail ◽  
Eman Khalifa ◽  
Shaimaa A. Abd El-Kader ◽  
Dalia Ibrahim Mohamed ◽  
...  
Keyword(s):  
Growth Performance ◽  
Clostridium Perfringens ◽  
Broiler Chickens ◽  
Body Weight Gain ◽  
Economic Benefits ◽  
Production Costs ◽  
Broiler Chicks ◽  
Necrotic Enteritis ◽  
Feed Conversion ◽  
Intestinal Lesion

Necrotic enteritis (NE) caused by Clostridium perfringens (C. perfringens) results in impaired bird growth performance and increased production costs. Nanotechnology application in the poultry industry to control NE outbreaks is still not completely clarified. Therefore, the efficacy of dietary garlic nano-hydrogel (G-NHG) on broilers growth performance, intestinal integrity, economic returns and its potency to alleviate C. perfringens levels using NE challenge model were addressed. A total of 1200 male broiler chicks (Ross 308) were assigned into six groups; four supplemented with 100, 200, 300 or 400 mg of G-NHG/kg diet and co-challenged with C. perfringens at 21, 22 and 23 d of age and two control groups fed basal diet with or without C. perfringens challenge. Over the total growing period, the 400 mg/kg G-NHG group had the most improved body weight gain and feed conversion efficiency regardless of challenge. Parallel with these results, the mRNA expression of genes encoding digestive enzymes (alpha 2A amylase (AMY2A), pancreatic lipase (PNLIP) and cholecystokinin (CCK)) and intestinal barriers (junctional adhesion molecule-2 (JAM-2), occludin and mucin-2 (Muc-2)) were increased in groups fed G-NHG at higher levels to be nearly similar to those in the unchallenged group. At 14 d post challenge, real-time PCR results revealed that inclusion of G-NHG led to a dose-dependently decrease in the C. perfringens population, thereby decreasing the birds’ intestinal lesion score and mortality rates. Using 400 mg/kg of G-NHG remarkably ameliorated the adverse effects of NE caused by C. perfringens challenge, which contributed to better growth performance of challenged birds with rational economic benefits.

scholarly journals Symmetrically substituted dichlorophenes inhibit N-acyl-phosphatidylethanolamine phospholipase D

2020 ◽  
Vol 295 (21) ◽  
pp. 7289-7300 ◽  
Author(s):  
Geetika Aggarwal ◽  
Jonah E. Zarrow ◽  
Zahra Mashhadi ◽  
C. Robb Flynn ◽  
Paige Vinson ◽  
...  
Keyword(s):  
Bile Acids ◽  
Phospholipase D ◽  
Cultured Cells ◽  
Lithocholic Acid ◽  
Hek293 Cells ◽  
Serum Lipase ◽  
Structure Activity ◽  
Molecule Inhibitor ◽  
Streptomyces Chromofuscus

N-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of N-acyl-ethanolamides. Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a lack of effective NAPE-PLD inhibitors has been a major obstacle to elucidating the role of NAPE-PLD and N-acyl-ethanolamide biosynthesis in these processes. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (with an IC50 of 68 μm), but LCA is also a highly potent ligand for TGR5 (EC50 0.52 μm). Recently, the first selective small-molecule inhibitor of NAPE-PLD, ARN19874, has been reported (having an IC50 of 34 μm). To identify more potent inhibitors of NAPE-PLD, here we used a quenched fluorescent NAPE analog, PED-A1, as a substrate for recombinant mouse Nape-pld to screen a panel of bile acids and a library of experimental compounds (the Spectrum Collection). Muricholic acids and several other bile acids inhibited Nape-pld with potency similar to that of LCA. We identified 14 potent Nape-pld inhibitors in the Spectrum Collection, with the two most potent (IC50 = ∼2 μm) being symmetrically substituted dichlorophenes, i.e. hexachlorophene and bithionol. Structure–activity relationship assays using additional substituted dichlorophenes identified key moieties needed for Nape-pld inhibition. Both hexachlorophene and bithionol exhibited significant selectivity for Nape-pld compared with nontarget lipase activities such as Streptomyces chromofuscus PLD or serum lipase. Both also effectively inhibited NAPE-PLD activity in cultured HEK293 cells. We conclude that symmetrically substituted dichlorophenes potently inhibit NAPE-PLD in cultured cells and have significant selectivity for NAPE-PLD versus other tissue-associated lipases.

scholarly journals Symmetrically substituted dichlorophenes inhibit N-acyl-phosphatidylethanolamine phospholipase D

2020 ◽  
Author(s):  
Geetika Aggarwal ◽  
Jonah E. Zarrow ◽  
Zahra Mashhadi ◽  
C. Robb Flynn ◽  
Paige Vinson ◽  
...  
Keyword(s):  
Bile Acids ◽  
Phospholipase D ◽  
Lithocholic Acid ◽  
Hek293 Cells ◽  
Serum Lipase ◽  
Physiological Processes ◽  
Structure Activity ◽  
Molecule Inhibitor ◽  
Expression And Activity

AbstractN-acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of N-acyl-ethanolamides (NAEs). Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a major obstacle to elucidating the role of NAPE-PLD and NAE biosynthesis in various physiological processes has been the lack of effective NAPE-PLD inhibitors. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (IC50 68 μM) but LCA is also a highly potent ligand for TGR5 (EC50 0.52 μM). Recently, the first selective small molecule inhibitor of NAPE-PLD, ARN19874, was reported (IC50 34 μM). To identify more potent inhibitors of NAPE-PLD, we screened compounds using a quenched fluorescent NAPE analog, PED-A1, as a substrate for recombinant mouse NAPE-PLD. Screened compounds included a panel of bile acids as well as a library of experimental compounds (the Spectrum Collection). Muricholic acids and several other bile acids inhibited NAPE-PLD with potency similar to LCA. Fourteen potent NAPE-PLD inhibitors were identified in the Spectrum Collection, with the two most potent (IC50 ~2 μM) being symmetrically substituted dichlorophenes: hexachlorophene and bithionol. Structure activity relationship assays using additional substituted dichlorophenes identified key moieties needed for NAPE-PLD inhibition. Both hexachlorophene and bithionol showed significant selectivity for NAPE-PLD compared to non-target lipase activities such as S. chromofuscus PLD activity or serum lipase activity. Both also effectively inhibited NAPE-PLD activity in cultured HEK293 cells.

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.

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.

The function of multidrug resistance-associated protein 3 in the transport of bile acids under normal physiological and lithocholic acid-induced cholestasis conditions

2021 ◽  
Vol 22 ◽  
Author(s):  
Wenyu Wang ◽  
Sijing Zeng ◽  
Ming Hu ◽  
Zhongqiu Liu ◽  
Lingzhi Gong
Keyword(s):  
Multidrug Resistance ◽  
Bile Acid ◽  
Bile Acids ◽  
Physiological Condition ◽  
Lithocholic Acid ◽  
Efflux Transporters ◽  
Valuable Insight ◽  
Wild Type ◽  
Normal Physiological Condition

Background: The role of multidrug resistance-associated protein 3 (Mrp3) in the transport of bile acid (BA) in drug-induced cholestasis have not been well studied. Objective: In this study, wild type and Mrp3 knockout (Mrp3-/- ) mice under normal physiological and lithocholic acid (LCA)-induced cholestatic conditions were employed to investigate the role of Mrp3 in BA transport. Method: The levels of BA in serum, liver, gallbladder, intestine, kidney, feces and urine were quantified in both wild type and Mrp3-/- mice via ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-MS/MS). Quantitative real time PCR (RT-PCR) analysis was used to measure the expression of genes related to the transport and synthesis of BA. Results: The results showed that the liver did not suffer more serious damage as a result of cholestasis when Mrp3 was depleted. The level of some individual bile acids changed apparently in the compartments of enterohepatic circulation (EHC) between the two control and model groups, respectively, but the level of serum total bile acid was only slightly reduced for Mrp3-/- groups. In addition, the level of BA-related efflux transporters and synthases increased significantly when Mrp3 was knocked out under normal physiological condition, but negligible alteration of them appeared under cholestatic condition. Conclusion: Our results indicated that Mrp3 could be responsible for the transport of some specific bile acids, and part of the Mrp3 role could be compensated for by other transporters. Moreover, Mrp3 deficiency has a direct effect on the expression of BA-related synthases and efflux transporters under normal physiological condition, but this effect could be less prominent under cholestatic condition. This study could provide much valuable insight into the physiological function of Mrp3 in the transport of bile acids.

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 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 Potential Role of Amino Acids in the Adaptation of Chicks and Market-Age Broilers to Heat Stress

2021 ◽  
Vol 7 ◽  
Author(s):  
Vishwajit S. Chowdhury ◽  
Guofeng Han ◽  
Hatem M. Eltahan ◽  
Shogo Haraguchi ◽  
Elizabeth R. Gilbert ◽  
...  
Keyword(s):  
Amino Acids ◽  
Heat Stress ◽  
Stress Responses ◽  
The Body ◽  
Economic Losses ◽  
Broiler Chicks ◽  
Poultry Production ◽  
In Ovo ◽  
Air Temperatures

Increased average air temperatures and more frequent and prolonged periods of high ambient temperature (HT) associated with global warming will increasingly affect worldwide poultry production. It is thus important to understand how HT impacts poultry physiology and to identify novel approaches to facilitate improved adaptation and thereby maximize poultry growth, health and welfare. Amino acids play a role in many physiological functions, including stress responses, and their relative demand and metabolism are altered tissue-specifically during exposure to HT. For instance, HT decreases plasma citrulline (Cit) in chicks and leucine (Leu) in the embryonic brain and liver. The physiological significance of these changes in amino acids may involve protection of the body from heat stress. Thus, numerous studies have focused on evaluating the effects of dietary administration of amino acids. It was found that oral l-Cit lowered body temperature and increased thermotolerance in layer chicks. When l-Leu was injected into fertile broiler eggs to examine the cause of reduction of Leu in embryos exposed to HT, in ovo feeding of l-Leu improved thermotolerance in broiler chicks. In ovo injection of l-Leu was also found to inhibit weight loss in market-age broilers exposed to chronic HT, giving rise to the possibility of developing a novel biotechnology aimed at minimizing the economic losses to poultry producers during summer heat stress. These findings and the significance of amino acid metabolism in chicks and market-age broilers under HT are summarized and discussed in this review.

scholarly journals Bacillus subtilis DSM29784 Alleviates Negative Effects on Growth Performance in Broilers by Improving the Intestinal Health Under Necrotic Enteritis Challenge

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanyuan Wang ◽  
Yibin Xu ◽  
Shengliang Xu ◽  
Jinyong Yang ◽  
Kaiying Wang ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Growth Performance ◽  
Economic Losses ◽  
Broiler Chicks ◽  
Necrotic Enteritis ◽  
Negative Effects ◽  
Treatment Groups ◽  
Beneficial Effects ◽  
Intestinal Lesions ◽  
Colony Forming Units

Along with banning antibiotics, necrotic enteritis (NE), especially subclinical enteritis (SNE), poses a significant threat to the chicken industry; however, probiotics are a potentially promising intervention. We aimed to investigate the beneficial effects of Bacillus subtilis DSM29784 (BS) on the treatment of Clostridium perfringens (CP)-induced SNE in broilers. A total of 360 1-day-old broiler chicks were divided into three treatment groups, namely control (Ctr), SNE, and BS treatment (BST) groups, all of which were fed with a basal died for 21days, and then from day 22 onward, only the BST group had a BS supplemented diet (1×109 colony-forming units BS/kg). On day 15, all chicks, except the Ctr group, were challenged with a 20-fold dose coccidiosis vaccine and 1ml CP (2×108) on days 18–21 for SNE induction. Beneficial effects were observed on growth performance in BST compared to SNE broilers. BST treatment alleviated intestinal lesions and increased the villus height/crypt depth ratio. Further, BST broilers showed increased maltase activity in the duodenum compared with SNE chicks, and a significantly decreased caspase-3 protein expression in the jejunum mucosa. Moreover, an increased abundance of Ruminococcaceae and Bifidobacterium beneficial gut bacteria and an altered gut metabolome were observed. Taken together, we demonstrate that the manipulation of microbial gut composition using probiotics may be a promising prevention strategy for SNE by improving the composition and metabolism of the intestinal microbiota, intestinal structure, and reducing inflammation and apoptosis. Hence, BS potentially has active ingredients that may be used as antibiotic substitutes and effectively reduces the economic losses caused by SNE. The findings of this study provide a scientific foundation for BS application in broiler feed in the future.

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