scholarly journals Investigation of Microencapsulated BSH ActiveLactobacillusin the Simulated Human GI Tract

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Christopher Martoni ◽  
Jasmine Bhathena ◽  
Mitchell Lawrence Jones ◽  
Aleksandra Malgorzata Urbanska ◽  
Hongmei Chen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Bile Salt ◽  
Oral Delivery ◽  
Bile Salt Hydrolase ◽  
Residence Times ◽  
Bacterial Cells ◽  
Gi Tract ◽  
Bile Salt Deconjugation ◽  
Computer Controlled

This study investigated the use of microencapsulated bile salt hydrolase (BSH) overproducingLactobacillus plantarum80 cells for oral delivery applications using a dynamic computer-controlled model simulating the human gastrointestinal (GI) tract. Bile salt deconjugation rates for microencapsulated BSH overproducing cells were 4.87±0.28 μmol/g microcapsule/h towards glycoconjugates and 0.79±0.15 μmol/g microcapsule/h towards tauroconjugates in the simulated intestine, a significant (P<.05) increase over microencapsulated wild-type cells. Microcapsules protected the encased cells in the simulated stomach prior to intestinal release, maintaining cell viability above109 cfu/mL at pH 2.5 and 3.0 and above106 cfu/mL at pH 2.0 after 2-hour residence times. In the simulated intestine, encased cell viability was maintained above1010 cfu/mL after 3, 6, and 12-hour residence times in bile concentrations up to 1.0%. Results show that microencapsulation has potential in the oral delivery of live BSH active bacterial cells. However,in vivotesting is required.

scholarly journals Functional Analysis of Four Bile Salt Hydrolase and Penicillin Acylase Family Members in Lactobacillus plantarum WCFS1

2008 ◽  
Vol 74 (15) ◽  
pp. 4719-4726 ◽  
Author(s):  
Jolanda M. Lambert ◽  
Roger S. Bongers ◽  
Willem M. de Vos ◽  
Michiel Kleerebezem
Keyword(s):  
Bile Salt ◽  
Lactobacillus Plantarum ◽  
Bile Salts ◽  
Natural Habitat ◽  
Penicillin Acylase ◽  
Exponential Growth Phase ◽  
Bile Salt Hydrolase ◽  
Intestinal Microbes ◽  
Bsh Activity

ABSTRACT Bile salts play an important role in the digestion of lipids in vertebrates and are synthesized and conjugated to either glycine or taurine in the liver. Following secretion of bile salts into the small intestine, intestinal microbes are capable of deconjugating the glycine or taurine from the bile salts, using an enzyme called bile salt hydrolase (Bsh). Intestinal lactobacilli are regarded as major contributors to bile salt hydrolysis in vivo. Since the bile salt-hydrolyzing strain Lactobacillus plantarum WCFS1 was predicted to carry four bsh genes (bsh1, bsh2, bsh3, and bsh4), the functionality of these bsh genes was explored using Lactococcus lactis heterologous overexpression and multiple bsh deletion strains. Thus, Bsh1 was shown to be responsible for the majority of Bsh activity in L. plantarum WCFS1. In addition, bsh1 of L. plantarum WCFS1 was shown to be involved in conferring tolerance to specific bile salts (i.e., glycocholic acid). Northern blot analysis established that bsh1, bsh2, bsh3, and bsh4 are all expressed in L. plantarum WCFS1 during the exponential growth phase. Following biodiversity analysis, bsh1 appeared to be the only bsh homologue that was variable among L. plantarum strains; furthermore, the presence of bsh1 correlated with the presence of Bsh activity, suggesting that Bsh1 is commonly responsible for Bsh activity in L. plantarum strains. The fact that bsh2, bsh3, and bsh4 genes appeared to be conserved among L. plantarum strains suggests an important role of these genes in the physiology and lifestyle of the species L. plantarum. Analysis of these additional bsh-like genes in L. plantarum WCFS1 suggests that they might encode penicillin acylase rather than Bsh activity, indicating their implication in the conversion of substrates other than bile acids in the natural habitat.

scholarly journals The effects of different plant extracts on bile salt hydrolase activity of Lactobacillus strains isolated from the gastrointestinal tract of poultry

2021 ◽  
Vol 91 (1) ◽  
pp. 89-99
Author(s):  
Amin Dibamehr ◽  
◽  
Mohsen Daneshyar ◽  
Amir Tukmechi ◽  
Seyyed Meysam Abtahi Froushani
Keyword(s):  
Bile Salt ◽  
Green Tea ◽  
Plant Extracts ◽  
Enzymatic Reaction ◽  
Antibacterial Properties ◽  
Feed Additives ◽  
Poultry Feed ◽  
Bile Salt Hydrolase ◽  
Promising Alternative

The bile salt hydrolysis (BSH) enzyme weakens fat metabolism through bile salt deconjugation and reduces poultry performance, in order to cope with the antibacterial properties of the bile. Therefore, reducing the activity of this enzyme through the use of feed additives is probably a promising alternative to antibiotics for improving poultry performance. Plant extracts have long been used as feed additives for promoting poultry growth. In the current experiment, five Lactobacillus strains including Lactobacillus animalis, Lactobacillus acidophillus, Lactobacillus gallinarum, Lactobacillus lactis, and Lactobacillus returi were obtained from the poultry hindgut and were used as the probiotic application. A plate test and two-step enzymatic reaction method were used for deconjugation activity determination of the Lactobacillus strains. Further, four plant extracts (i.e., the aerial parts of Rosemary (Rosmarinus officinalis), Roselle calyx (Hibiscus sabdariffa), Berberis vulgaris root, and Green tea) were examined in terms of BSH enzyme inhibitors using the cell-free extracts as the potential antibiotic alternative. Furthermore, the gallbladders of the broilers were freshly collected from the poultry slaughterhouses, and their contents were extracted. The results showed that all Lactobacillus strains could hydrolyze the taurocholate acid (TCA) and chicken bile salt mixture (CBSM) to unconjugated bile acid. Moreover, ethanolic extracts of B. vulgaris root and Green tea relatively reduced the activity of the BSH enzyme that could potentially be investigated as an appropriate alternative in poultry feed in vivo. In conclusion, all five Lactobacillus strains were resistant to bile salts (i.e. TCA and CBSM) by BSH activity, and the addition of Green tea and B. vulgaris root extracts to the bacterial medium demonstrated inhibitory effects against the BSH enzyme.

scholarly journals An ingestible self-orienting system for oral delivery of macromolecules

Science ◽  
2019 ◽  
Vol 363 (6427) ◽  
pp. 611-615 ◽  
Author(s):  
Alex Abramson ◽  
Ester Caffarel-Salvador ◽  
Minsoo Khang ◽  
David Dellal ◽  
David Silverstein ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Active Pharmaceutical Ingredient ◽  
Drug Uptake ◽  
In Vivo Studies ◽  
Gi Tract ◽  
Pharmaceutical Ingredients ◽  
Model Drug ◽  
Poor Absorption ◽  
Systemic Drug

Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise’s ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator’s safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.

Cholesterol-lowering potentials of Lactobacillus strain overexpression of bile salt hydrolase on high cholesterol diet-induced hypercholesterolemic mice

2019 ◽  
Vol 10 (3) ◽  
pp. 1684-1695 ◽  
Author(s):  
Guangqiang Wang ◽  
Wenli Huang ◽  
Yongjun Xia ◽  
Zhiqiang Xiong ◽  
Lianzhong Ai
Keyword(s):  
Bile Salt ◽  
Lactobacillus Strain ◽  
Bile Salt Hydrolase ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Cholesterol Lowering

Lactobacillus strain overexpression of bile salt hydrolase can exert a cholesterol-reducing effect in vivo.

scholarly journals Development of a Covalent Inhibitor of Gut Bacterial Bile Salt Hydrolases

2019 ◽  
Author(s):  
Arijit A. Adhikari ◽  
Tom C. Seegar ◽  
Scott B. Ficarro ◽  
Megan D. McCurry ◽  
Deepti Ramachandran ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Unmet Need ◽  
Cysteine Residue ◽  
Gut Bacteria ◽  
Bile Salt Hydrolase ◽  
Secondary Bile Acid ◽  
Bsh Activity

AbstractBile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria in order to study the effects of bile acids on host physiology. Here, we report the development of a covalent pan-inhibitor of gut bacterial BSH. From a rationally designed candidate library, we identified a lead compound bearing an alpha-fluoromethyl ketone warhead that modifies BSH at the catalytic cysteine residue. Strikingly, this inhibitor abolished BSH activity in conventional mouse feces. Mice gavaged with a single dose of this compound displayed decreased BSH activity and decreased deconjugated bile acid levels in feces. Our studies demonstrate the potential of a covalent BSH inhibitor to modulate bile acid composition in vivo.

scholarly journals Investigation of Genipin Cross-Linked Microcapsule for Oral Delivery of Live Bacterial Cells and Other Biotherapeutics: Preparation and In Vitro Analysis in Simulated Human Gastrointestinal Model

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Hongmei Chen ◽  
Wei Ouyang ◽  
Christopher Martoni ◽  
Fatemeh Afkhami ◽  
Bisi Lawuyi ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Oral Therapy ◽  
Model Material ◽  
Bacterial Cells ◽  
Gi Tract ◽  
Viable Cells ◽  
Vitro Analysis ◽  
Live Bacterial Cells ◽  
In Vitro Analysis

Oral therapy utilizing engineered microorganisms has shown promise in the treatment of many diseases. By microencapsulation, viable cells can overcome the harsh gastrointestinal (GI) environment and secrete needed therapeutics into the gut. These engineered cells should be encased without escaping into the GI tract for safety concerns, thus robust microcapsule membrane is requisite. This paper examined the GI performance of a novel microcapsule membrane using a dynamic simulated human GI model. Results showed that the genipin cross-linked alginate-chitosan (GCAC) microcapsules possessed strong resistance to structural disintegration in the simulated GI environment. Leakage of encapsulated high molecular weight dextran, a model material to be protected during the simulated GI transit, was negligible over 72 h of exposure, in contrast to considerable leakage of dextran from the non-cross-linked counterparts. These microcapsules did not alter the microflora and enzymatic activities in the simulated human colonic media. This study suggested the potential of the GCAC microcapsules for oral delivery of live microorganisms and other biotherapeutics.

Screening of Bile Salt Hydrolase-Active Lactic Acid Bacteria for Potential Cholesterol-Lowering Probiotic Use

2011 ◽  
Vol 345 ◽  
pp. 139-146 ◽  
Author(s):  
Chun Feng Guo ◽  
Lan Wei Zhang ◽  
Jing Yan Li ◽  
Ying Chun Zhang ◽  
Chao Hui Xue ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Bile Salt ◽  
Enterococcus Faecium ◽  
Lactobacillus Casei ◽  
Acid Resistance ◽  
Bile Salt Hydrolase ◽  
Cholesterol Lowering ◽  
Reduce Serum Cholesterol ◽  
Bile Salt Deconjugation

.Cholesterol-lowering effect of lactic acid bacteria (LAB) with bile salt hydrolase activity is well known. In this study, 150 LAB were screened for bile salt deconjugation ability and probiotic characters. Fourteen isolates with higher bile salt deconjugation ability were initially screened out using deconjugation rate above 50% as standard. These isolates were further screened for adhesion to HT-29 cells, bile tolerance and acid resistance. Four isolates, namely Lactobacillus casei F0822, Lactobacillus casei F0422, Enterococcus faecium F0511 and Enterococcus faecium IN7.12, was finally screened out. The 4 isolates may be able to reduce serum cholesterol levels in human and thus have a potential to apply in the biomedicine field.

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