Christopher Martoni

Cholesterol-lowering efficacy of a microencapsulated bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 yoghurt formulation in hypercholesterolaemic adults.

Several studies have reported limited or no reduction in serum cholesterol in response to probiotic formulations. Recently, probiotics have shown promise in treating metabolic disease due to improved strain selection and delivery technologies. The aim of the present study was to evaluate the cholesterol-lowering efficacy of a yoghurt formulation containing microencapsulated bile salt hydrolase (BSH)-active Lactobacillus reuteri NCIMB 30242, taken twice per d over 6 weeks, in hypercholesterolaemic adults. A total of 114 subjects completed this double-blind, placebo-controlled, randomised, parallel-arm, multi-centre study. This interventional study included a 2-week washout, 2-week run-in and 6-week treatment period. Subjects were randomised to consume either yoghurts containing microencapsulated L. reuteri NCIMB 30242 or placebo yoghurts. Over the intervention period, subjects consuming yoghurts containing microencapsulated L. reuteri NCIMB 30242 attained significant reductions in LDL-cholesterol (LDL-C) of 8·92 % (P = 0·016), total cholesterol (TC) of 4·81 % (P = 0·031) and non-HDL-cholesterol (HDL-C) of 6·01 % (P = 0·029) over placebo, and a significant absolute change in apoB-100 of - 0·19 mmol/l (P = 0·049). Serum concentrations of TAG and HDL-C were unchanged over the course of the study. Present results show that consumption of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurt is efficacious and safe for lowering LDL-C, TC, apoB-100 and non-HDL-C in hypercholesterolaemic subjects. The efficacy of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurts appears to be superior to traditional probiotic therapy and akin to that of other cholesterol-lowering ingredients.

In vitro study of alginate-chitosan microcapsules : an alternative to liver cell transplants for the treatment of liver failure

The application of alginate–chitosan (AC) microcapsules to liver cell transplantation has not been previously investigated. In the current in vitro study, we have investigated the potential of AC microcapsules for the encapsulation of liver cells and show that the AC membrane supports the survival, proliferation and protein secretion by entrapped hepatocytes. The AC membrane provides cell immuno-isolation and has the potential for cell cryopreservation. The AC microcapsule has several advantages compared to more widely used alginate–poly-L-lysine (APA) microcapsules for the application of cell therapy.

Erratum of “Investigation of Microencapsulated BSH Active Lactobacillus in the Simulated Human GI Tract”

This is to confirm that there is an error in the article “Investigation of Microencapsulated BSH Active Lactobacillus in the Simulated Human GI Tract” by Martoni et al. Published online December 25, 2007, doi: 10.1155/2007/13684. Figure 5 should be replaced by Figure 5 below. Figure 5 Evaluation of microcapsule integrity and morphological changes during simulated GI transit. (a) Pre-stomach transit (b) Post-stomach transit (60 minutes) (c) Post-stomach (60 minutes) and intestinal (10 hours) transit.Microcapsule size (a) 608 ± ...

Cholesterol lowering with bile salt hydrolase-active probiotic bacteria, mechanism of action, clinical evidence, and future direction for heart health applications.

Introduction: Cardiovascular diseases (CVD) are the leading cause of global mortality and morbidity. Current CVD treatment methods include dietary intervention, statins, fibrates, niacin, cholesterol absorption inhibitors, and bile acid sequestrants. These formulations have limitations and, thus, additional treatment modalities are needed. Probiotic bacteria, especially bile salt hydrolase (BSH)-active probiotic bacteria, have demonstrated cholesterol-lowering efficacy in randomized controlled trials. Areas covered: This review describes the current treatments for CVD and the need for additional therapeutics. Gut microbiota etiology of CVD, cholesterol metabolism, and the role of probiotic formulations as therapeutics for the treatment and prevention of CVD are described. Specifically, we review studies using BSH-active bacteria as cholesterol-lowering agents with emphasis on their cholesterol-lowering mechanisms of action. Potential limitations and future directions are also highlighted. Expert opinion: Numerous clinical studies have concluded that BSH-active probiotic bacteria, or products containing them, are efficient in lowering total and low-density lipoprotein cholesterol. However, the mechanisms of action of BSH-active probiotic bacteria need to be further supported. There is also the need for a meta-analysis to provide better information regarding the therapeutic use of BSH-active probiotic bacteria. The future of BSH-active probiotic bacteria most likely lies as a combination therapy with already existing treatment options.

The human microbiome and bile acid metabolism: dysbiosis, dysmetabolism, disease and intervention

Introduction: Recent evidence indicates that the human gut microbiome plays a significant role in health and disease. Dysbiosis, defined as a pathological imbalance in a microbial community, is becoming increasingly appreciated as a ‘central environmental factor’ that is both associated with complex phenotypes and affected by host genetics, diet and antibiotic use. More recently, a link has been established between the dysmetabolism of bile acids (BAs) in the gut to dysbiosis. Areas covered: BAs, which are transformed by the gut microbiota, have been shown to regulate intestinal homeostasis and are recognized as signaling molecules in a wide range of metabolic processes. This review will examine the connection between BA metabolism as it relates to the gut microbiome and its implication in health and disease. Expert opinion: A disrupted gut microbiome, including a reduction of bile salt hydrolase (BSH)-active bacteria, can significantly impair the metabolism of BAs and may result in an inability to maintain glucose homeostasis as well as normal cholesterol breakdown and excretion. To better understand the link between dysbiosis, BA dysmetabolism and chronic degenerative disease, large-scale metagenomic sequencing studies, metatranscriptomics, metaproteomics and metabolomics should continue to catalog functional diversity in the gastrointestinal tract of both healthy and diseased populations. Further, BSH-active probiotics should continue to be explored as treatment options to help restore metabolic levels.

Estimation of the Potential Antitumor Activity of Microencapsulated Lactobacillus acidophilus Yogurt Formulation in the Attenuation of Tumorigenesis in Apc(Min/+) Mice

There is a strong correlation between orally administered probiotics and suppression of the low-grade inflammation that can lead to restoration of normal local immune functions. We studied the potential immunomodulatory and antitumorigenic properties of microencapsulated probiotic bacterial cells in a yogurt formulation in Min mice carrying a germline APC mutation. Daily oral administration of microencapsulated Lactobacillus acidophilus bacterial cells in the yogurt formulation mice resulted in significant suppression of colon tumor incidence, tumor multiplicity, and reduced tumor size. Results show that oral administration of microencapsulated L. acidophilus contributed to the stabilization of animal body weight and decreased the release of bile acids. Histopathological analyses revealed fewer adenomas in treated versus untreated animals. Furthermore, treated animals exhibited fewer gastrointestinal intra-epithelial neoplasias with a lower grade of dysplasia in detected tumors. Results suggest that oral administration of microencapsulated probiotic L. acidophilus exerts anti-tumorous activity, which consequently leads to reduced tumor outcome.

Orally delivered microencapsulated live probiotic formulation lowers serum lipids in hypercholesterolemic hamsters.

Elevated serum cholesterol is a major risk factor for coronary artery disease. Nutritional therapies such as probiotics have been suggested to manage elevated cholesterol. This study investigates the cholesterol and triglyceride lowering potential of a microencapsulated feruloyl esterase-producing Lactobacillus fermentum 11976 (LF11976) probiotic formulation. Male Bio F(1)B hamsters were assigned to two groups to receive either the microcapsule probiotic formulation (containing LF11976 cells at 12.51 log colony-forming units/mL) or placebo formulation (empty) microcapsules, twice daily, by oral gavage for 18 weeks. For the duration of the study, animals were fed a hypercholesterolemic diet. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and the atherogenic index were 21.36%, 31.43%, and 32.59% lower in the group gavaged with the microencapsulated probiotic formulation than in the placebo control group after 18 weeks (P < .05). Histology studies showed reduced progression of atherosclerotic lesions in animals treated with microencapsulated LF11976 as compared to control animals. Treatment with microencapsulated LF11976 formulation produces significant reductions in serum total cholesterol, LDL cholesterol, and serum triglyceride levels in diet-induced hypercholesterolemic hamsters. Findings suggest the potential of the oral microencapsulated probiotic cell formulation as a functional nutritional alternative for managing excessive serum cholesterol and triglyceride levels.

Preparation and characterization of novel polymeric microcapsules for live cell encapsulation and therapy.

This article describes the preparation and in vitro characterization of novel genipin cross-linked alginate-chitosan (GCAC) microcapsules that have potential for live cell therapy applications. This microcapsule system, consisting of an alginate core with a covalently cross-linked chitosan membrane, was formed via ionotropic gelation between calcium ions and alginate, followed by chitosan coating by polyelectrolyte complexation and covalent cross-linking of chitosan by naturally derived genipin. Results showed that, using this design concept and the three-step procedure, spherical GCAC microcapsules with improved membrane strength, suppressed capsular swelling, and suitable permeability can be prepared. The suitability of this novel membrane formulation for live cell encapsulation was evaluated, using bacterial Lactobacillus plantarum 80 (pCBH1) (LP80) and mammalian HepG2 as model cells. Results showed that capsular integrity and bacterial cell viability were sustained 6 mo postencapsulation, suggesting the feasibility of using this microcapsule formulation for lives bacterial cell encapsulation. The metabolic activity of the encapsulated HepG2 was also investigated. Results suggested the potential capacity of this GCAC microcapsule in cell therapy and the control of cell signaling; however, further research is required.

Investigation of Microencapsulated BSH Active Lactobacillus in the Simulated Human GI Tract

This study investigated the use of microencapsulated bile salt hydrolase (BSH) overproducing Lactobacillus plantarum 80 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 above 109 cfu/mL at pH 2.5 and 3.0 and above 106 cfu/mL at pH 2.0 after 2-hour residence times. In the simulated intestine, encased cell viability was maintained above 1010 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 vivo testing is required.

Evaluation of clinical safety and tolerance of a Lactobacillus reuteri NCIMB 30242 supplement capsule: a randomized control trial.

A significant number of human clinical trials have reported no adverse effects associated with consumption of Lactobacillus reuteri (L. reuteri). In the present study, the clinical safety and toxicology of oral ingestion of supplement capsules containing L. reuteri NCIMB 30242 was investigated. A randomized group of 131 subjects received a dose of 2.9×10⁹ CFU L. reuteri NCIMB 30242 capsules (n=67) or placebo capsules (n=64) twice daily for 9 weeks. Clinical chemistry and hematological parameters of safety were analyzed. The frequency, duration and intensity of adverse events (AE)s and clinical significance of safety parameters were recorded for both groups. No clinically significant differences between the probiotic capsule and placebo capsule treated groups were detected in either the blood clinical chemistry or hematology results. The frequency and intensity of AEs was similar in the two groups. These results demonstrate that administration of a twice daily dose of 2.9×10⁹ CFU was safe and well tolerated in the population evaluated over 9 weeks.