Patricia Martorell

Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases Lifespan in Caenorhabditis elegans

Numerous studies have shown that resistance to oxidative stress is crucial to stay healthy and to reduce the adverse effects of aging. Accordingly, nutritional interventions using antioxidant food-grade compounds or food products are currently an interesting option to help improve health and quality of life in the elderly. Live lactic acid bacteria (LAB) administered in food, such as probiotics, may be good antioxidant candidates. Nevertheless, information about LAB-induced oxidative stress protection is scarce. To identify and characterize new potential antioxidant probiotic strains, we have developed a new functional screening method using the nematode Caenorhabditis elegans as host. C. elegans were fed on different LAB strains (78 in total) and nematode viability was assessed after oxidative stress (3 mM and 5 mM H2O2). One strain, identified as Lactobacillus rhamnosus CNCM I-3690, protected worms by increasing their viability by 30% and, also, increased average worm lifespan by 20%. Moreover, transcriptomic analysis of C. elegans fed with this strain showed that increased lifespan is correlated with differential expression of the DAF-16/insulin-like pathway, which is highly conserved in humans. This strain also had a clear anti-inflammatory profile when co-cultured with HT-29 cells, stimulated by pro-inflammatory cytokines, and co-culture systems with HT-29 cells and DC in the presence of LPS. Finally, this Lactobacillus strain reduced inflammation in a murine model of colitis. This work suggests that C. elegans is a fast, predictive and convenient screening tool to identify new potential antioxidant probiotic strains for subsequent use in humans.

Use of Saccharomyces cerevisiae and Caenorhabditis elegans as Model Organisms To Study the Effect of Cocoa Polyphenols in the Resistance to Oxidative Stress

Developing functional foods to improve the quality of life for elderly people has great economic and social impact. Searching for and validating ingredients with in vivo antioxidant effects is one of the key steps in developing this kind of food. Here we describe the combined use of simple biological models and transcriptomics to define the functional intracellular molecular targets of a polyphenol-enriched cocoa powder. Cocoa powder supplemented culture medium led to increased resistance to oxidative stress, in both the budding yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans, and, in the latter, lifespan was also increased. These effects are fully dependent on the polyphenols present in the cocoa powder and on the sirtuins Hst3 (yeast) and SIR-2.1 (worm). The transcription factor DAF-16 also plays an important role in the case of the nematode, indicating that the insulin/IGF-1 (insulin-like growth factor) signaling pathway is related with the antioxidative effect of cocoa polyphenols. All in all, these results confirm that this polyphenol-enriched cocoa powder, with antioxidant activity, has great potential use as a functional food ingredient for elderly people. Furthermore, this work reveals the value of using simple biological models to screen for compounds that are of interest for the food and pharmacological industry.

A cocoa peptide protects Caenorhabditis elegans from oxidative stress and β-amyloid peptide toxicity.

Background Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases. Methodology/Principal Findings A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aβ1–42 peptide as a pre-clinical in vivo model for Alzheimers disease. Among the peptides isolated, peptide 13L (1 µg/mL) showed the highest antioxidant activity (P≤0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24–47 h period after Aβ1–42 peptide induction (P≤0.0001). This observation is in accordance with the reduction of Aβ deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide. Conclusions/Significance These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aβ deposition in a C. elegans model of Alzheimers disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals.

A novel antioxidant beverage for body weight control based on coffee silverskin

The present research aimed to add value to coffee silverskin by looking for new innovative applications. Formulation of novel beverages based on coffee silverskin for body fat reduction and body weight control was proposed. Conditions for beverage preparation were optimised. Data on chemical composition and sensorial quality of the new drink were acquired. Health benefits were evaluated in vitro and in vivo employing as animal model Caenorhabditis elegans. An antioxidant beverage containing physiological active concentrations of caffeine and chlorogenic acid for prevention body fat accumulation and possessing acceptable sensorial properties was obtained. Our findings support that the use of coffee silverskin for obtaining bioactive extract is an innovative way for revalorisation of coffee by-product.

Caenorhabditis elegans as a Model To Study the Effectiveness and Metabolic Targets of Dietary Supplements Used for Obesity Treatment: The Specific Case of a Conjugated Linoleic Acid Mixture (Tonalin)

The antiobesity effect of conjugated linoleic acid (CLA) has previously been described in different animal models. The aim of the present study was to investigate the effect of a commercial mixture (Tonalin) on Caenorhabditis elegans to assess their potential use for functional ingredient screenings. Body-fat reduction with Tonalin was demonstrated in wild-type strain N2. The 1 μg/mL dose was the most effective, either alone or added to a food matrix, and also significantly decreased triglyceride content in nematodes fed on the CLA mixture. Furthermore, the antiobesity effect was related to the CLA isomer trans-10, cis-12. Finally, the transcriptional study showed C. elegans fed with Tonalin (1 μg/mL) underwent an upregulation of energy metabolism, reproduction, protein metabolism and oxidative stress processes. In conclusion, the results presented here clearly correlate well with other animal studies, demonstrating the value of C. elegans as a useful model to evaluate antiobesity compounds/ingredients.

Coffee Silverskin Extract Protects against Accelerated Aging Caused by Oxidative Agents.

Nowadays, coffee beans are almost exclusively used for the preparation of the beverage. The sustainability of coffee production can be achieved introducing new applications for the valorization of coffee by-products. Coffee silverskin is the by-product generated during roasting, and because of its powerful antioxidant capacity, coffee silverskin aqueous extract (CSE) may be used for other applications, such as antiaging cosmetics and dermaceutics. This study aims to contribute to the coffee sector’s sustainability through the application of CSE to preserve skin health. Preclinical data regarding the antiaging properties of CSE employing human keratinocytes and Caenorhabditis elegans are collected during the present study. Accelerated aging was induced by tert-butyl hydroperoxide (t-BOOH) in HaCaT cells and by ultraviolet radiation C (UVC) in C. elegans. Results suggest that the tested concentrations of coffee extracts were not cytotoxic, and CSE 1 mg/mL gave resistance to skin cells when oxidative damage was induced by t-BOOH. On the other hand, nematodes treated with CSE (1 mg/mL) showed a significant increased longevity compared to those cultured on a standard diet. In conclusion, our results support the antiaging properties of the CSE and its great potential for improving skin health due to its antioxidant character associated with phenols among other bioactive compounds present in the botanical material.

Probiotic Strain Bifidobacterium animalis subsp. lactis CECT 8145 Reduces Fat Content and Modulates Lipid Metabolism and Antioxidant Response in Caenorhabditis elegans

Recently, microbial changes in the human gut have been proposed as a possible cause of obesity. Therefore, modulation of microbiota through probiotic supplements is of great interest to support obesity therapeutics. The present study examines the functional effect and metabolic targets of a bacterial strain, Bifidobacterium animalis subsp. lactis CECT 8145, selected from a screening in Caenorhabditis elegans. This strain significantly reduced total lipids (40.5% ± 2.4) and triglycerides (27.6% ± 0.5), exerting antioxidant effects in the nematode (30% ± 2.8 increase in survival vs control); activities were also preserved in a final food matrix (milk). Furthermore, transcriptomic and metabolomic analyses in nematodes fed with strain CECT 8145 revealed modulation of the energy and lipid metabolism, as well as the tryptophan metabolism (satiety), as the main metabolic targets of the probiotic. In conclusion, our study describes for the first time a new B. animalis subsp. lactis strain, CECT 8145, as a promising probiotic for obesity disorders. Furthermore, the data support future studies in obesity murine models.

Draft Genome Sequence of Bifidobacterium animalis subsp. lactis Strain CECT 8145, Able To Improve Metabolic Syndrome In Vivo

ABSTRACT Bifidobacterium animalis subsp. lactis strain CECT 8145 is able to reduce body fat content and improve metabolic syndrome biomarkers. Here, we report the draft genome sequence of this strain, which may provide insights into its safety status and functional role.

A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid β peptide toxicity in Caenorhabditis elegans

Abstract Lactoferrin is a highly multifunctional glycoprotein involved in many physiological functions, including regulation of iron absorption and immune responses. Moreover, there is increasing evidence for neuroprotective effects of lactoferrin. We used Caenorhabditis elegans as a model to test the protective effects, both on phenotype and transcriptome, of a nutraceutical product based on lactoferrin liposomes. In a dose‐dependent manner, the lactoferrin‐based product protected against acute oxidative stress and extended lifespan of C. elegans N2. Furthermore, Paralysis of the transgenic C. elegans strain CL4176, caused by Aβ1‐42 aggregates, was clearly ameliorated by treatment. Transcriptome analysis in treated nematodes indicated immune system stimulation, together with enhancement of processes involved in the oxidative stress response. The lactoferrin‐based product also improved the protein homeostasis processes, cellular adhesion processes, and neurogenesis in the nematode. In summary, the tested product exerts protection against aging and neurodegeneration, modulating processes involved in oxidative stress response, protein homeostasis, synaptic function, and xenobiotic metabolism. This lactoferrin‐based product is also able to stimulate the immune system, as well as improving reproductive status and energy metabolism. These findings suggest that oral supplementation with this lactoferrin‐based product could improve the immune system and antioxidant capacity. Further studies to understand the molecular mechanisms related with neuronal function would be of interest.

Bioprospecting the solar panel microbiome: high-throughput screening for antioxidant bacteria in a Caenorhabditis elegans model

Microbial communities that are exposed to sunlight typically share a series of adaptations to deal with the radiation they are exposed to, including efficient DNA repair systems, pigment production and protection against oxidative stress, which makes these environments good candidates for the search of novel antioxidant microorganisms. In this research project, we isolated potential antioxidant pigmented bacteria from a dry and highly-irradiated extreme environment: solar panels. High-throughput in vivo assays using Caenorhabiditis elegans as an experimental model demonstrated the high antioxidant and ultraviolet-protection properties of these bacterial isolates that proved to be rich in carotenoids. Our results suggest that solar panels harbor a microbial community that includes strains with potential applications as antioxidants.