O'Hagan C.,University of Cardiff |
Li J.V.,Imperial College London |
Marchesi J.R.,Imperial College London |
Marchesi J.R.,University of Cardiff |
And 3 more authors.
Neurobiology of Learning and Memory | Year: 2017
Ageing is associated with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and production of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixture (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioural flexibility in 15–17-month-old male rats. Following behavioural testing, the hippocampus and prefrontal cortex was extracted and analysed ex vivo using 1H nuclear magnetic resonance (1H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place associations. Short–term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. 1H NMR analysis revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory. © 2017 Elsevier Inc.
Kohling H.L.,University of Duisburg - Essen |
Kohling H.L.,Cultech Ltd. |
Plummer S.F.,Cultech Ltd. |
Marchesi J.R.,University of Cardiff |
And 3 more authors.
Clinical Immunology | Year: 2017
Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject. © 2017 Elsevier Inc.
PubMed | University of Swansea and Cultech Ltd
Type: Journal Article | Journal: Archives of disease in childhood | Year: 2014
To evaluate a multistrain, high-dose probiotic in the prevention of eczema.A randomised, double-blind, placebo-controlled, parallel group trial.Antenatal clinics, research clinic, children at home.Pregnant women and their infants.Women from 36weeks gestation and their infants to age 6months received daily either the probiotic (Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subspecies lactis CUL34 and Bifidobacterium bifidum CUL20; total of 10(10) organisms/day) or matching placebo.Diagnosed eczema at age 2years. Infants were followed up by questionnaire. Clinical examination and skin prick tests to common allergens were done at 6months and 2years.The cumulative frequency of diagnosed eczema at 2years was similar in the probiotic (73/214, 34.1%) and placebo arms (72/222, 32.4%; OR 1.07, 95% CI 0.72 to 1.6). Among the secondary outcomes, the cumulative frequency of skin prick sensitivity at 2years was reduced in the probiotic (18/171; 10.5%) compared with the placebo arm (32/173; 18.5%; OR 0.52, 95% CI 0.28 to 0.98). The statistically significant differences between the arms were mainly in sensitisation to cows milk and hens egg proteins at 6months. Atopic eczema occurred in 9/171 (5.3%) children in the probiotic arm and 21/173 (12.1%) in the placebo arm (OR 0.40, 95% CI 0.18 to 0.91).The study did not provide evidence that the probiotic either prevented eczema during the study or reduced its severity. However, the probiotic seemed to prevent atopic sensitisation to common food allergens and so reduce the incidence of atopic eczema in early childhood.ISRCTN26287422.
SEROYAL United States INC. and Cultech Ltd | Date: 2012-10-23
Preparations and substances for naturopathic or therapeutic use, namely, capsules and tablets for use in the treatment of conditions arising from yeast and fungal infections and imbalances in the natural microflora; vitamin and mineral preparations and substances, namely, vitamin and mineral supplements.
PubMed | Comenius University, R.Ø.S.A. and Cultech Ltd
Type: | Journal: Free radical biology & medicine | Year: 2015
Assessment of the cardiovascular disease (CVD) risk factors in children can predict clinical manifestations of atherosclerosis in adulthood. The arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1) and lipid parameters (Total cholesterol (TCH), VLDL-cholesterol (VLDL), triacylglycerols (TAG), HDL-cholesterol (HDL), LDL-cholesterol (LDL) and LDL- and HDL-subfractions and their mutual associations in 27 hypercholesterolemic children and adolescents were investigated.Serum levels of TCH and TAG were determined using a Hitachi 911 analyser (Roche Diagnostics, Switzerland). LDL- and HDL-subfractions were determined by Lipoprint system (Quantimetrix, Corp., USA). PON1-A and PON1-L activities were determined according to Gan et al. (1991) and Aviram and Rosenblat (2008).PON1-A activity was higher compared to healthy children (134.126.2 vs. 118.167.05 U/ml) and PON1-L was not different from healthy controls. Increased levels of atherogenic risk factors TCH, VLDL, IDL1 subfraction and decreased levels of the antiatherogenic IDL3 and LDL1 subfractions were observed in the hypercholesterolemic children compared to reference values. Increased levels of large HDL subfractions, comparable levels of intermediate HDL and lower levels of small HDL subfractions were observed in hypercholesterolemic children compared to healthy adults (in absence of data available for healthy children). No significant correlation between PON1-A and HDL subfractions was found. PON1-L activity positively correlated with antiatherogenic large HDL1 subfraction and negatively correlated with intermediate HDL4, 5 and 6 subfractions.The findings suggest that the PON1-L activity rather than PON1-A activity play a protective role in atherosclerosis. We confirmed atheroprotective effect of large and atherogenic properties of small HDL subfractions. The intermediate HDL subfractions probably play no atheroprotective role.
Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2013-IAPP | Award Amount: 1.19M | Year: 2014
Graves orbitopathy (GO), also known as thyroid eye disease, affects approximately 3 million people in Europe with an estimated socioeconomic burden of 6.4 billion euros per annum. GO is a complication of Graves disease which is an autoimmune disease and the commonest cause of an overactive thyroid gland. The treatment of GO remains unsatisfactory and the majority of patients report long-term impairment of quality of life. To improve the outcomes of people with GO and thus reduce long-term illness and cost to society, research is needed to address the identification of risk factors, develop a better understanding of the pathophysiology of the disease, devise approaches for early diagnosis during the pre-clinical stage of the disease, and create novel and safe interventions. INDIGO will refine and optimise animal and in vitro models of Graves disease and GO, which are urgently required to facilitate the study of the pathogenesis of GO. INDIGO will address the identification of risk factors for the initiation and perpetuation of autoimmunity that causes disease, using the latest generation technologies to study variations in the microbiome in Graves and GO patients and controls. The interaction of the gut derived antigens, from micro-organisms and nutrients on the autoimmune response in both the animal model by probiotic and contra-biotic intervention. State of the art technology will be used to search for biomarkers that will identify patients that will progress to GO, during the preclinical phase of the disease when intervention is most likely to be successful. The successful completion of the project will be ensured by a partnership involving 2 SMEs, 3 academic institutions and the European Group on Graves Orbitopathy, each contributing complementary expertise and technology, the project will involve 5 secondments and 3 recruitments that will facilitate the exchange of knowledge and training.
Corfe B.M.,University of Sheffield |
Harden C.J.,University of Sheffield |
Bull M.,University of Cardiff |
Garaiova I.,Cultech Ltd.
Proceedings of the Nutrition Society | Year: 2015
The recent availability of high-throughput nucleic acid sequencing technologies has rapidly advanced approaches to analysing the role of the gut microbiome in governance of human health, including gut health, and also metabolic, cardiovascular and mental health, inter alia. Recent scientific studies suggest that energy intake (EI) perturbations at the population level cannot account for the current obesity epidemic, and significant work is investigating the potential role of the microbiome, and in particular its metabolic products, notably SCFA, predominantly acetate, propionate and butyrate, the last of which is an energy source for the epithelium of the large intestine. The energy yield from dietary residues may be a significant factor influencing energy balance. This review posits that the contribution towards EI is governed by EI diet composition (not just fibre), the composition of the microbiome and by the levels of physical activity. Furthermore, we hypothesise that these factors do not exist in a steady state, but rather are dynamic, with both short- and medium-term effects on appetite regulation. We suggest that the existing modelling strategies for bacterial dynamics, specifically for growth in chemostat culture, are of utility in understanding the dynamic interplay of diet, activity and microbiomic organisation. Such approaches may be informative in optimising the application of dietary and microbial therapy to promote health. Copyright © The Authors 2015.
Lloyd D.,University of Cardiff |
Williams C.F.,Cultech Ltd.
Molecular and Biochemical Parasitology | Year: 2014
The diplomonad genera are here represented by three highly diverse species, both free-living (Hexamita inflata), and parasitic (Spironucleus vortens and Giardia intestinalis). All three are moderately aerotolerant flagellates, inhabiting environments where O2 tensions are low and fluctuating. Many diplomonads are opportunistic pathogens of avian, terrestrial and aquatic animals. Hexamitids inhabit deep waters and sediments of lakes and marine basins, S. vortens commonly infects the intestinal tract of ornamental fish, particularly of cichlids and cyprinids, and G. intestinalis, the upper intestinal tracts of humans as well as domestic and farm animals. Despite these very different habitats, their known physiological and biochemical characteristics are similar, but they do differ in significant respects as their lifestyles and life cycles demand. They have efficient O2 scavenging systems, and are highly effective at countering rapid O2 fluctuations, or clustering away from its source (except for G. intestinalis when attached to the jejunal villi). Their core metabolic pathways (glycolysis using pyrophosphate), incomplete tricarboxylic acid cycle (lacking α-ketoglutarate dehydrogenase), and amino acid metabolism (with an alternative energy-generating arginine dihydrolase pathway as a possibility in some cases), largely conform to those of other protists inhabiting low-O2 environments. Mitochondrial evolutionary reduction to give hydrogenosomes as seen in Spironucleus spp. has proceeded further to its minimal state in the mitosomes of G. intestinalis. Understanding of essential redox reactions and the maintentence of redox state, especially in the infective encysted stage of G. intestinalis provide increasing possibilities for parasite control. To this aim a plethora of new synthetic chemicals and natural products (especially those from garlic, Allium sativum) show promise as replacements for the highly effective (but potentially toxic to higher organisms) 5-nitroimidazoles (e.g., metronidazole) in the treatment and/or prevention of dimplomonad infection in humans and animals. © 2014 Elsevier Ltd. All rights reserved.
Moss J.W.E.,University of Cardiff |
Davies T.S.,University of Cardiff |
Garaiova I.,Cultech Ltd |
Plummer S.F.,Cultech Ltd |
And 2 more authors.
PLoS ONE | Year: 2016
Introduction Atherosclerosis is the underlying cause of cardiovascular disease that leads to more global mortalities each year than any other ailment. Consumption of active food ingredients such as phytosterols, omega-3 polyunsaturated fatty acids and flavanols are known to impart beneficial effects on cardiovascular disease although the combined actions of such agents in atherosclerosis is poorly understood. The aim of this study was to screen a nutritional supplement containing each of these active components for its anti-atherosclerotic effect on macrophages in vitro. Results The supplement attenuated the expression of intercellular adhesion molecule-1 and macrophage chemoattractant protein-1 in human and murine macrophages at physiologically relevant doses. The migratory capacity of human monocytes was also hindered, possibly mediated by eicosapentaenoic acid and catechin, while the ability of foam cells to efflux cholesterol was improved. The polarisation of murine macrophages towards a proinflammatory phenotype was also attenuated by the supplement. Conclusion The formulation was able to hinder multiple key steps of atherosclerosis development in vitro by inhibiting monocyte recruitment, foam cell formation and macrophage polarisation towards an inflammatory phenotype. This is the first time a combination these ingredients has been shown to elicit such effects and supports its further study in preclinical in vivo models. © 2016 Moss et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PubMed | Comenius University, Juvenalia Paediatric Center and Cultech Ltd
Type: Journal Article | Journal: Acta biochimica Polonica | Year: 2016
The Lipoprint system (Quantimetrix Corp., CA, USA), enables the determination of 10 high density lipoprotein (HDL) subfractions in contrast to the 5 HDL subfractions that can be determined by ultracentrifuge analysis. HDL subfractions, and their relationships to the arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1), together with total-, very low density lipoprotein- and low density lipoprotein (LDL)-cholesterol and LDL subfractions were investigated in the serum of 27 mildly hypercholesterolemic children and 21 healthy controls. Our results suggest the antiatherogenity of large HDL (L-HDL) subfractions and the atherogenity of small HDL (S-HDL) subfractions in the study groups. However, the relationship between the intermediate HDL (I-HDL) subfractions with the LDL subfractions and other lipoproteins did not suggest that I-HDL subfractions are antiatherogenic. No significant association between PON1-A and the HDL subfractions was found. In contrast, PON1-L activity positively correlated with the antiatherogenic large HDL1 subfraction and negatively with intermediate HDL subfractions 4, 5 and 6. Our results contribute to the knowledge of the roles of total HDL and ten individual HDL subfractions in children and adolescents.