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3. Inorganic phosphate modifies stationary phase fitness and metabolic pathways in Lactiplantibacillus paraplantarum CRL 1905

Author

Mario Araoz, Mariana Grillo-Puertas, Alejandra de Moreno de LeBlanc, Elvira María Hebert, Josefina María Villegas, and Viviana Andrea Rapisarda

Subjects
lactic acid bacteria, stationary phase, polyphosphate, proteomics, biofilm, Microbiology, QR1-502
Abstract

Inorganic phosphate (Pi) concentration modulates polyphosphate (polyP) levels in diverse bacteria, affecting their physiology and survival. Lactiplantibacillus paraplantarum CRL 1905 is a lactic acid bacterium isolated from quinoa sourdough with biotechnological potential as starter, for initiating fermentation processes in food, and as antimicrobial-producing organism. The aim of this work was to evaluate the influence of the environmental Pi concentration on different physiological and molecular aspects of the CRL 1905 strain. Cells grown in a chemically defined medium containing high Pi (CDM + P) maintained elevated polyP levels up to late stationary phase and showed an enhanced bacterial survival and tolerance to oxidative stress. In Pi sufficiency condition (CDM-P), cells were ~ 25% longer than those grown in CDM + P, presented membrane vesicles and a ~ 3-fold higher capacity to form biofilm. Proteomic analysis indicated that proteins involved in the “carbohydrate transport and metabolism” and “energy production and conversion” categories were up-regulated in high Pi stationary phase cells, implying an active metabolism in this condition. On the other hand, stress-related chaperones and enzymes involved in cell surface modification were up-regulated in the CDM-P medium. Our results provide new insights to understand the CRL 1905 adaptations in response to differential Pi conditions. The adjustment of environmental Pi concentration constitutes a simple strategy to improve the cellular fitness of L. paraplantarum CRL 1905, which would benefit its potential as a microbial cell factory.

Published
2024
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4. Oral administration of a probiotic Lactobacillus modulates cytokine production and TLR expression improving the immune response against Salmonella enterica serovar Typhimurium infection in mice

Author

Perdigón Gabriela, Castillo Natalia A, and de Moreno de LeBlanc Alejandra

Subjects
Microbiology, QR1-502
Abstract

Abstract Background Diarrheal infections caused by Salmonella, are one of the major causes of childhood morbidity and mortality in developing countries. Salmonella causes various diseases that range from mild gastroenteritis to enteric fever, depending on the serovar involved, infective dose, species, age and immune status of the host. Probiotics are proposed as an attractive alternative possibility in the prevention against this pathogen infection. Previously we demonstrated that continuous Lactobacillus casei CRL 431 administration to BALB/c mice before and after challenge with Salmonella enterica serovar Typhimurium (S. Typhimurium) decreased the severity of Salmonella infection. The aim of the present work was to deep into the knowledge about how this probiotic bacterium exerts its effect, by assessing its impact on the expression and secretion of pro-inflammatory (TNFα, IFNγ) and anti-inflammatory (IL-10) cytokines in the inductor and effector sites of the gut immune response, and analyzing toll-like receptor (TLR2, TLR4, TLR5 and TLR9) expressions in both healthy and infected mice. Results Probiotic administration to healthy mice increased the expression of TLR2, TLR4 and TLR9 and improved the production and secretion of TNFα, IFNγ and IL-10 in the inductor sites of the gut immune response (Peyer's patches). Post infection, the continuous probiotic administration, before and after Salmonella challenge, protected the host by modulating the inflammatory response, mainly in the immune effector site of the gut, decreasing TNFα and increasing IFNγ, IL-6 and IL-10 production in the lamina propria of the small intestine. Conclusions The oral administration of L. casei CRL 431 induces variations in the cytokine profile and in the TLRs expression previous and also after the challenge with S. Typhimurium. These changes show some of the immune mechanisms implicated in the protective effect of this probiotic strain against S. Typhimurium, providing an alternative way to reduce the severity of the infection.

Published
2011
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5. Impact of a probiotic fermented milk in the gut ecosystem and in the systemic immunity using a non-severe protein-energy-malnutrition model in mice

Author

Carmuega Esteban, de Moreno de LeBlanc Alejandra, Núñez Ivanna, Galdeano Carolina, Weill Ricardo, and Perdigón Gabriela

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Malnutrition affects the immune response, causing a decrease of defence mechanisms and making the host more susceptible to infections. Probiotics can reconstitute the intestinal mucosa and stimulate local and systemic immunity. The aim of this work was evaluate the effects of a probiotic fermented milk as a complement of a re-nutrition diet, on the recovery of the intestinal barrier, and mucosal and systemic immune functions in a murine model of non-severe protein-energy-malnutrition. Its potential protection against Salmonella enterica serovar Typhimurium (S. Typhimurium) infection was also analyzed. Methods Mice were undernourished and divided into 3 groups according to the dietary supplement received during re-nutrition (milk, probiotic fermented milk or its bacterial free supernatant) and compared to well-nourished and malnourished mice. They were sacrificed previous to the re-nutrition and 5 days post re-nutrition. The phagocytic activity of macrophages from spleen and peritoneum and the changes in the intestinal histology and microbiota were evaluated. Different immune cell populations and cytokine productions were analyzed in the small intestine tissues. The effect of the re-nutrition supplements on the systemic immunity using OVA antigen and against an infection with S. Typhimurium was also studied. Results Probiotic fermented milk was the most effective re-nutrition diet that improved the intestinal microbiota. Its administration also increased the number of IgA+ cells, macrophages and dendritic cells. The production of different cytokine (IFN-γ, TNF-α, IL-12) by these cells and the phagocytic activity in peritoneum and spleen was also increased. This re-nutrition diet also stimulated the systemic immune response against OVA antigen which was diminished after the malnutrition period and also improved the host response against S. Typhimurium, decreasing the spread of pathogenic bacteria to the liver and the spleen. The importance of the metabolites released during milk fermentation was also demonstrated through the analysis of the bacterial free supernatant obtained from the probiotic fermented milk, but the whole product showed the best effects in the parameters evaluated in this study. Conclusions The administration of probiotic fermented milk as a dietary supplement during the re-nutrition process in a murine immunodeficiency model by malnutrition could be a good adjuvant diet to improve the gut and systemic immune response for the protection against Salmonella infection.

Published
2011
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6. Effect of the administration of a fermented milk containing Lactobacillus casei DN-114001 on intestinal microbiota and gut associated immune cells of nursing mice and after weaning until immune maturity

Author

Carmuega Esteban, Galdeano Carolina, Dogi Cecilia A, de Moreno de LeBlanc Alejandra, Weill Ricardo, and Perdigón Gabriela

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Microbial colonization of the intestine after birth is an important step for the development of the gut immune system. The acquisition of passive immunity through breast-feeding may influence the pattern of bacterial colonization in the newborn. The aim of this work was to evaluate the effect of the administration of a probiotic fermented milk (PFM) containing yogurt starter cultures and the probiotic bacteria strain Lactobacillus casei DN-114001 to mothers during nursing or their offspring, on the intestinal bacterial population and on parameters of the gut immune system. Results Fifteen mice of each group were sacrificed at ages 12, 21, 28 and 45 days. Large intestines were taken for determination of intestinal microbiota, and small intestines for the study of secretory-IgA (S-IgA) in fluid and the study of IgA+ cells, macrophages, dendritic cells and goblet cells on tissue samples. The consumption of the PFM either by the mother during nursing or by the offspring after weaning modified the development of bifidobacteria population in the large intestine of the mice. These modifications were accompanied with a decrease of enterobacteria population. The administration of this PFM to the mothers improved their own immune system and this also affected their offspring. Offspring from mice that received PFM increased S-IgA in intestinal fluids, which mainly originated from their mother's immune system. A decrease in the number of macrophages, dendritic cells and IgA+ cells during the suckling period in offspring fed with PFM was observed; this could be related with the improvement of the immunity of the mothers, which passively protect their babies. At day 45, the mice reach maturity of their own immune system and the effects of the PFM was the stimulation of their mucosal immunity. Conclusion The present work shows the beneficial effect of the administration of a PFM not only to the mothers during the suckling period but also to their offspring after weaning and until adulthood. This effect positively improved the intestinal microbiota that are related with a modulation of the gut immune response, which was demonstrated with the stimulation of the IgA + cells, macrophages and dendritic cells.

Published
2008
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9. Beneficial Effects of Lactobacilli Species on Intestinal Homeostasis in Low-Grade Inflammation and Stress Rodent Models and Their Implication in the Modulation of the Adhesive Junctional Complex

Author

Célia Chamignon, Geoffroy Mallaret, Julie Rivière, Marthe Vilotte, Sead Chadi, Alejandra de Moreno de LeBlanc, Jean Guy LeBlanc, Frédéric Antonio Carvalho, Marco Pane, Pierre-Yves Mousset, Philippe Langella, Sophie Lafay, and Luis G. Bermúdez-Humarán

Subjects
leaky gut, chronic diseases, barrier functions, probiotics, Lactobacillus, Microbiology, QR1-502
Abstract

Intestinal barrier integrity is essential in order to maintain the homeostasis of mucosal functions and efficient defensive reactions against chemical and microbial challenges. An impairment of the intestinal barrier has been observed in several chronic diseases. The gut microbiota and its impact on intestinal homeostasis is well described and numerous studies suggest the ability of some probiotic strains to protect the intestinal epithelial integrity and host homeostasis. In this work, we aimed to assess the beneficial effects of three Lactobacillus strains (Lacticaseibacillus rhamnosus LR04, Lacticaseibacillus casei LC03, and Lactiplantibacillus plantarum CNCM I-4459) and their mechanism of action in low-grade inflammation or neonatal maternal separation models in mice. We compared the impact of these strains to that of the well-known probiotic Lacticaseibacillus rhamnosus GG. Our results demonstrated that the three strains have the potential to restore the barrier functions by (i) increasing mucus production, (ii) restoring normal permeability, and (iii) modulating colonic hypersensitivity. Moreover, gene expression analysis of junctional proteins revealed the implication of Claudin 2 and Cingulin in the mechanisms that underlie the interactions between the strains and the host. Taken together, our data suggest that LR04, CNCM I-4459, and LC03 restore the functions of an impaired intestinal barrier.

Published
2023
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13. Maternal dietary omega-3 deficiency worsens the deleterious effects of prenatal inflammation on the gut-brain axis in the offspring across lifetime

Author

Leyrolle, Q., Decoeur, F., Briere, G., Amadieu, C., Quadros, A. R. A. A., Voytyuk, I., Lacabanne, C., Benmamar-Badel, A., Bourel, J., Aubert, A., Sere, A., Chain, F., Schwendimann, L., Matrot, B., Bourgeois, T., Grégoire, S., Leblanc, J. G., De Moreno De Leblanc, A., Langella, P., Fernandes, G. R., Bretillon, L., Joffre, C., Uricaru, R., Thebault, P., Gressens, P., Chatel, J. M., Layé, S., and Nadjar, A.

Published
2021
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18. List of contributors

Author

Aadil, Rana Muhammad, primary, Adegoke, Samuel Chetachukwu, additional, Ahmad, Aziz, additional, Ahmad, Talha, additional, Ahmad Magry, Muneer, additional, Ahmed, Waqar, additional, Aksun Tümerkan, Elif Tuğçe, additional, Ala-Rämi, Katariina, additional, Albuquerque, Marcela Albuquerque Cavalcanti de, additional, Albuquerque, Tânia Gonçalves, additional, Alexandri, Maria, additional, Álvarez-Castillo, Estefanía, additional, Alves, Rita Carneiro, additional, Annegowda, H.V., additional, Ascenso, A., additional, Ayala-Zavala, J. Fernando, additional, Barragán-Huerta, Blanca E., additional, Barretti, Barbara Ruivo Valio, additional, Bengoechea, Carlos, additional, Bento, M., additional, Bhat, Rajeev, additional, Bhushan, Brij, additional, Bhuyan, Nilutpal, additional, Blaise, D., additional, Brooks, Marianne Su-Ling, additional, Caligiani, Augusta, additional, Campos-Vega, Rocio, additional, Carvalheiro, M., additional, Cavalheiro, Carlos Pasqualin, additional, Ceballos-Duque, S.M., additional, Chakkaravarthi, Saravanan, additional, Choo, Wee Sim, additional, Choudhury, Nabajit Dev, additional, Chuah, Wei Chean, additional, Chuen, Ng Lee, additional, Chye, Fook Yee, additional, Costa, A., additional, Costa, Helena S., additional, da Cruz, Adriano Gomes, additional, da Silva, Maurício Costa Alves, additional, da Silva Araújo, Íris Braz, additional, de Carvalho, Julio Cesar, additional, de Medeiros, Igor Ucella Dantas, additional, de Moreno de LeBlanc, Alejandra, additional, de Souza, Simone Lorena Quitério, additional, Dey, Gargi, additional, do Nascimento Alves, Rerisson, additional, Dufoo-Hurtado, Elisa, additional, Enríquez-Valencia, Salma A., additional, Faria-Silva, A.C., additional, Felix, Manuel, additional, Fichtner, Maximilian, additional, Fierascu, Irina, additional, Fierascu, Radu Claudiu, additional, Fowler, Scott W., additional, Franco, Bernadette Dora Gombossy de Melo, additional, Garcia-Ortega, Maria Patricia Guerrero, additional, Ghazali, Mohd Sabri Mohd, additional, Gonçalves, L.M., additional, González, Almudena González, additional, González-Aguilar, Gustavo A., additional, Gore, Anil H., additional, Goswami, Luna, additional, Goula, Athanasia M., additional, Guerrero, Antonio, additional, Guimarães, Jonas Toledo, additional, Gunjal, Datta B., additional, Gutiérrez-Macías, Paulina, additional, Hassim, Muhamad Fairus Noor, additional, Herrero, Ana M., additional, Jinadasa, B.K.K.K., additional, Kataki, Rupam, additional, Khan, Moazzam Rafiq, additional, Kikas, Timo, additional, Kloth, Marcela, additional, Kolekar, Govind B., additional, Kourmentza, Konstantina, additional, Koutinas, Apostolis, additional, Krebsz, Melinda, additional, Krishna C. Doddapaneni, Tharaka Rama, additional, Kumar, Sonia, additional, Lacerda, Luiz Gustavo, additional, LeBlanc, Jean Guy, additional, Lehtinen, Ulla, additional, Leni, Giulia, additional, Leong, Boon Fung, additional, Long, Jade M., additional, Lopez, Christelle, additional, López-Martínez, Leticia X., additional, Luzardo-Ocampo, Ivan, additional, Macedo, Gabriela A., additional, Maicas, Sergi, additional, Maina, Sofia, additional, Majumder, Pulak, additional, Maldonado-Celis, Ma. Elena, additional, Marques, M., additional, Marto, J., additional, Mateo, José Juan, additional, Minakshi, Manickam, additional, Mirón-Mérida, Vicente A., additional, Mohan, Anand, additional, Moreda-Piñeiro, Antonio, additional, Moreira Fernandes Santos, Miriane, additional, Naik, Vaibhav M., additional, Narula, Sapna A., additional, Narzari, Rumi, additional, Nayak, Arunima, additional, Nikoo, Mehdi, additional, Nille, Omkar S., additional, Nunes, Patrícia, additional, Oliveira, M. Beatriz P.P., additional, Oomah, B. Dave, additional, Paiva, A., additional, Panda, Sandeep K., additional, Papapostolou, Harris, additional, Pasinszki, Tibor, additional, Patil, Akshay S., additional, Pereira Da Silva, Fábio Anderson, additional, Pharino, Chanathip, additional, Pimentel, Tatiana Colombo, additional, Ramos, Gustavo Luis de Paiva Anciens, additional, Ribeiro, H.M., additional, Rodríguez-Nava, C. Odín, additional, Ruiz-Capillas, Claudia, additional, Saad, Susana Marta Isay, additional, Saha, Niharendu, additional, Saik, Amy Yi Hsan, additional, Saikia, Ruprekha, additional, Santana, Ádina L., additional, Savitha, S., additional, Schneider, Philip A., additional, Seth, Dibyakanta, additional, Sforza, Stefano, additional, Shabbir, Muhammad Asim, additional, Sieniawska, Elwira, additional, Silva, Mafalda Alexandra, additional, Šimat, Vida, additional, Simões, P., additional, Simões, S., additional, Soccol, Carlos Ricardo, additional, Sydney, Alessandra Cristine Novak, additional, Sydney, Eduardo Bittencourt, additional, Tahergorabi, Reza, additional, Tsiviki, Maria, additional, Tsouko, Erminta, additional, Velmourougane, K., additional, Vendramel, Simone Maria Ribas, additional, Waghmare, Ravindra D., additional, Waghmare, V.N., additional, Wichienchot, Santad, additional, and Woiciechowski, Adenise Lorenci, additional

Published
2021
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22. Beneficial Effects of Lactobacilli Species on Intestinal Homeostasis in Low-Grade Inflammation and Stress Rodent Models and Their Implication in the Modulation of the Adhesive Junctional Complex

Author

Chamignon, Célia, primary, Mallaret, Geoffroy, additional, Rivière, Julie, additional, Vilotte, Marthe, additional, Chadi, Sead, additional, de Moreno de LeBlanc, Alejandra, additional, LeBlanc, Jean Guy, additional, Carvalho, Frédéric Antonio, additional, Pane, Marco, additional, Mousset, Pierre-Yves, additional, Langella, Philippe, additional, Lafay, Sophie, additional, and Bermúdez-Humarán, Luis G., additional

Published
2023
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23. Oral administration of milk fermented by Lactobacillus casei CRL431 was able to decrease metastasis from breast cancer in a murine model by modulating immune response locally in the lungs

Author

Virginia Emilce Mendez Utz, Gabriela Perdigón, and Alejandra de Moreno de LeBlanc

Subjects
Probiotic, Lung metastasis, Breast cancer, Immune response, Nutrition. Foods and food supply, TX341-641
Abstract

The host immune system is an important factor to combat metastasis. In this work, it was evaluated the immunomodulation exerted by milk fermented with the probiotic strain Lactobacillus casei CRL431 (PFM) when was administered to mice in the metastatic stage of breast cancer. Mice received PFM were compared to animals given milk. PFM administration diminished metastasis in the lungs and increased the survival of the animals. Systemically, PFM administration decreased pro-inflammatory cytokines and locally in the lungs (metastatic organs) decreased F4/80+ cells, principally IL-10/F4/80+ cells. The highest percentages for CD4+ and CD4+CD8+ cells were observed in PFM group. Finally, immune cells from lungs of mice given PFM showed lower production of most cytokines evaluated when they were re-stimulated in vitro with tumour cells. The results obtained suggest that modulation of immune cells in the lungs by PFM could be a strategy to fight against tumour cells in the metastatic sites.

Published
2019
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24. Tropical fruit by-products water extracts as sources of soluble fibres and phenolic compounds with potential antioxidant, anti-inflammatory, and functional properties

Author

Marcela Albuquerque Cavalcanti de Albuquerque, Romina Levit, Carolina Beres, Raquel Bedani, Alejandra de Moreno de LeBlanc, Susana Marta Isay Saad, and Jean Guy LeBlanc

Subjects
Probiotic, Fruit by-products, Dietary fibre, Phenolic compounds, Anti-inflammatory effect, Folate, Nutrition. Foods and food supply, TX341-641
Abstract

Fibre content, phenolic content, antioxidant and anti-inflammatory activities were evaluated for water extracts of fruit by-products (passion fruit, orange, acerola, and mango). The impact of these extracts on microbial growth, folate production, and adhesion ability of Streptococcus thermophilus TH-4 and Lactobacillus rhamnosus LGG was investigated. Mango water extract (MWE) presented the highest phenolic content and antioxidant activity. Orange water extract (OWE) and MWE showed the best anti-inflammatory potential by decreasing the highest nitric oxide levels. When TH-4 and LGG were grown together, folate production was only stimulated by MWE. Passion fruit water extract and OWE increased the TH-4 adhesion whereas acerola water extracts and MWE improved LGG adhesion when strains were used individually. These results showed that fruit by-product water extracts (FWE), especially from mango, presented potential beneficial biological and functional properties. These FWE could be used to develop new functional antioxidant foods and natural pharmaceutical ingredients.

Published
2019
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26. The Ability of Riboflavin-Overproducing Lactiplantibacillus plantarum Strains to Survive Under Gastrointestinal Conditions

Author

Annel M. Hernández-Alcántara, Sandra Pardo, Mari Luz Mohedano, Graciela M. Vignolo, Alejandra de Moreno de LeBlanc, Jean Guy LeBlanc, Rosa Aznar, and Paloma López

Subjects
lactic acid bacteria (LAB), riboflavin, protein mCherry, Lactiplantibacillus plantarum, tolerance to gastrointestinal stress of Lactiplantibacillus, Microbiology, QR1-502
Abstract

Riboflavin, vitamin B2, is essential for humans and has to be obtained from the diet. Some lactic acid bacteria (LAB) produce this vitamin, and they can be used for in-situ fortification of foods. This could be an alternative to supplementation with chemically synthesized vitamin, to palliate riboflavin deficiencies in specific groups of people. Moreover, if the producing LAB could survive in the gastrointestinal stress (GIT) they could be added as probiotics in this environment. In the present study we tested two riboflavin-overproducing Lactiplantibacillus plantarum strains (M5MA1-B2 and M9MG6-B2), spontaneous mutants of LAB isolated from chicha, a traditional Andean beverage. These two LAB, and also their isogenic strains M5MA1-B2[pRCR12] and M9MG6-B2[pRCR12], expressing the mCherry protein from the pRCR12 plasmid, were evaluated in vitro under simulated GIT conditions. Among other, specifically developed protein fluorescence assays were used. The four LAB showed similar levels of adhesion (>6.0%) to Caco-2 cells, higher than that of the probiotic Lacticaseibacillus rhamnosus GG strain (4.51%). Thus, LAB biofilm formation was assessed in the labeled cells by intracellular mCherry fluorescence and in the unlabeled parental strains by crystal violet staining. Both methods detected the formation of consistent biofilms by the L. plantarum strains. The quantification of mCherry fluorescence was also used to analyze LAB auto-aggregation properties. High levels of auto-aggregation were detected for both M5MA1-B2[pRCR12] and M9MG6-B2[pRCR12]. Survival of LAB included in a commercial cereal-based food matrix (Incaparina) under GIT conditions was also evaluated. The four LAB were resistant in vitro to the stomach and intestinal stresses, and proliferated in this environment, indicating a protective and nutritional effect of the Incaparina on the bacteria. Also, M9MG6-B2 survival in the presence or absence of Incaparina was evaluated in vivo in a BALB/c mouse model. The administration of the M9MG6-B2 strain alone or together with Incaparina had no adverse effect on the health, growth and/or well-being of the rodents. In addition, an increment in the villus length/crypt depth ratio was observed. The overall results obtained indicate that the LAB studied have probiotic characteristics of interest for the development of functional foods.

Published
2020
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27. Evaluation of the bioavailability and intestinal effects of milk fermented by folate producing lactic acid bacteria in a depletion/repletion mice model

Author

Ana Clara C. Cucick, Katia Gianni, Svetoslav D. Todorov, Alejandra de Moreno de LeBlanc, JeanGuy LeBlanc, and Bernadette D.G.M. Franco

Subjects
Folate, Vitamin deficiency, Lactic acid bacteria, Bioavailability, Fermented milk, Nutrition. Foods and food supply, TX341-641
Abstract

This study aimed to evaluate the bioavailability and effects on the intestinal mucosa of a bioenriched fermented milk (BFM) prepared with folate-producing lactic acid bacteria, using a depletion/repletion BALB/c mice model. Five Streptococcus thermophilus strains were combined with Lactobacillus plantarum 16cv and the combination that resulted in the best folate production was used for preparation of BFM. The folate content in BFM, prepared under controlled conditions (pH 6.0, 42 °C, 70 rpm, 24 h), was 321.1 ± 14.1 ng/mL. Results for mice fed with BFM were compared to those fed with other diets. The BFM group presented an increase in hemoglobin, hematocrit and red blood cells, and the villi height/crypt depth ratio was similar to that of animals receiving milk supplemented with commercial folic acid. The strains were sensitive to most tested antibiotics and lacked virulence genes, indicating that consumption of BFM may be a promising alternative to increase intake of folate.

Published
2020
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28. Probiotics and Trained Immunity

Author

Naima G. Cortes-Perez, Alejandra de Moreno de LeBlanc, Jorge G. Gomez-Gutierrez, Jean Guy LeBlanc, and Luis G. Bermúdez-Humarán

Subjects
probiotics, trained immunity, immune response, human health, Microbiology, QR1-502
Abstract

The characteristics of innate immunity have recently been investigated in depth in several research articles, and original findings suggest that innate immunity also has a memory capacity, which has been named “trained immunity”. This notion has revolutionized our knowledge of the innate immune response. Thus, stimulation of trained immunity represents a therapeutic alternative that is worth exploring. In this context, probiotics, live microorganisms which when administered in adequate amounts confer a health benefit on the host, represent attractive candidates for the stimulation of trained immunity; however, although numerous studies have documented the beneficial proprieties of these microorganisms, their mechanisms of action are not yet fully understood. In this review, we propose to explore the putative connection between probiotics and stimulation of trained immunity.

Published
2021
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30. Neuroprotective Effect of Riboflavin Producing Lactic Acid Bacteria in Parkinsonian Models

Author

Daiana Perez Visñuk, María del Milagro Teran, Graciela Savoy de Giori, Jean Guy LeBlanc, and Alejandra de Moreno de LeBlanc

Subjects
Male, Mice, Inbred C57BL, Disease Models, Animal, Mice, Cellular and Molecular Neuroscience, Neuroprotective Agents, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Lactobacillales, Dopaminergic Neurons, Riboflavin, Animals, General Medicine, Biochemistry
Abstract

Oxidative stress and inflammatory processes might contribute to the cascade of events leading Parkinson disease (PD); and vitamins such as riboflavin can exert protection on vulnerable neurons in neurodegenerative conditions. Previously, it was demonstrated that a mixture of lactic acid bacteria (including a riboflavin-producing strain) improved motor skills in a parkinsonian model. The aim of the present work was to investigate the neuroprotective potential of Lactiplantibacillus (L.) plantarum CRL2130, a riboflavin-producing strain in PD models. In vitro, N2a differentiated neurons were exposed the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or commercial riboflavin. In vivo, adult male C57BL/6 mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid, and received orally L. plantarum CRL2130, L. plantarum CRL725 (parent strain that produces low levels of riboflavin) or commercial vitamin. Results showed that when N2a cells were incubated with intracellular extract from L. plantarum CRL2130 maintained the viability, and significantly decreased the release of IL-6 and the formation of reactive oxygen species (ROS), all affected by MPP+. In vivo, the administration of L. plantarum CRL2130 attenuated motor deficits and prevented dopaminergic neuronal death. Decrease of pro-inflammatory cytokines and increase of IL-10 in both serum and brain were observed in samples from mice that received L. plantarum CRL2130 compared to MPTP control group (without treatment). In addition, these beneficial effects were similar or improved when compared with animals that received commercial riboflavin. In conclusion, L. plantarum CRL2130 showed a neuroprotective effect in both PD models through anti-oxidant/anti-inflammatory mechanisms.

Published
2022

31. Functional Food Biotechnology

Author

de Moreno de LeBlanc, Alejandra, primary, Luerce, Tessalia D., additional, Miyoshi, Anderson, additional, Azevedo, Vasco, additional, and LeBlanc, Jean Guy, additional

Published
2018
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32. List of Contributors

Author

García Yu, Irene Ai-Ling, primary, Alavi, Farhad, additional, AL-Ayadhi, Laila, additional, Albenzio, Marzia, additional, Alférez, Maria J.M., additional, Anadón, Arturo, additional, Ares, Irma, additional, Barancelli, Giovana V., additional, Bauman, Dale E., additional, Beck, Kathryn L., additional, Birch, John, additional, Bremer, Phil, additional, Burrow, Keegan, additional, Caldwell, Kathleen L., additional, Cardoso, Felipe C., additional, Carminati, Domenico, additional, Carne, Alan, additional, Caroprese, Mariangela, additional, Chia, Jade, additional, Chilibeck, Philip D., additional, Coad, Jane, additional, Collier, Robert J., additional, Conte, Giuseppe, additional, Corassin, Carlos H., additional, Da Silva, Marine S., additional, Day, Li, additional, de Melo Pereira, Gilberto V., additional, de Moreno de LeBlanc, Alejandra, additional, de Oliveira, Carlos Augusto F., additional, Diaz-Castro, Javier, additional, Duff, Whitney, additional, Bekhit, Alaa El-Din A., additional, Emam-Djomeh, Zahra, additional, Fernandes, Maurício J., additional, Galdeano, Carolina M., additional, Galhotra, Rohin, additional, Ghiasvand, Reza, additional, Gonçalves, Bruna L., additional, Halepoto, Dost M., additional, Hettinga, Kasper, additional, Iqbal, Furhan, additional, Jones, Robert L., additional, Kalebich, Caroline C., additional, Kalyankar, Shrikant D., additional, Kanca, Halit, additional, Kapila, Rajeev, additional, Kapila, Suman, additional, Khatoon, Humera, additional, Khedkar, Chaitali C., additional, Khedkar, Chandraprakash D., additional, Kontulainen, Saija, additional, Kumar, Naresh, additional, LeBlanc, Jean Guy, additional, Lee, Sarah H.I., additional, Levit, Romina, additional, López-Aliaga, Inmaculada, additional, Makhmudov, Amir, additional, Martínez-Larrañaga, María R., additional, Martínez, María A., additional, Mason, Sue, additional, McConnell, Michelle, additional, Mele, Marcello, additional, Miraghajani, Maryam, additional, Mizelman, Eliran, additional, Mohammadian, Mehdi, additional, Moreno-Fernandez, Jorge, additional, Morton, James D., additional, Najam, Rahela, additional, Nuñez, Ivanna N., additional, Oey, Indrawati, additional, Ozturkoglu-Budak, Sebnem, additional, Pagnoncelli, Maria G.B., additional, Parker, Alyssa M., additional, Patel, Ami R., additional, Perdigón, Gabriela, additional, Pereira, Paula C., additional, Polito, Anna N., additional, Pourmasoumi, Makan, additional, Raghavendra, Midathala, additional, Rashidinejad, Ali, additional, Recio-Rodríguez, José I., additional, Rudkowska, Iwona, additional, Salami, Maryam, additional, Samuelsson, Linda, additional, Sánchez-Aguadero, Natalia, additional, Santillo, Antonella, additional, Savoy de Giori, Graciela, additional, Serra, Andrea, additional, Shahbazi, Yasser, additional, Singal, Hari R., additional, Soccol, Carlos R., additional, Tanobe, Valcineide O.A., additional, Tidona, Flavio, additional, Tokas, Jayanti, additional, Turkmen, Nazli, additional, van Valenberg, Hein, additional, Vance, Kathryn A., additional, Vicente, Filipa, additional, Vij, Rishika, additional, Wang, Ye, additional, Watson, Ronald Ross, additional, Xiao, Yao, additional, and Young, Wayne, additional

Published
2018
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33. List of Contributors

Author

Afzaal, Hasan, primary, Ali, Amjad, additional, Ali, Zeeshan, additional, Arora, Jaspreet S., additional, Arunkumar, Kulanthaiyesu, additional, Azevedo, Marcela S.P., additional, Azevedo, Vasco, additional, Babar, Mustafeez M., additional, Barh, Debmalya, additional, Bisen, Kartikay, additional, Carvalho, Isabel S., additional, Chawla, Rekha, additional, Chinnannan, Karthik, additional, Coelho, Ana, additional, De Almeida, Sintia S., additional, De Castro Soares, Siomar, additional, de Moreno de LeBlanc, Alejandra, additional, De Sousa, Cassiana S., additional, Dubey, Rajesh K., additional, Grover, Atul, additional, Gul, Alvina, additional, Gupta, Sanjay M., additional, Hassan, Syed S., additional, Hassan, Yousef I., additional, Iqbal, Shahid, additional, Irfan, Rija, additional, Jadaun, Jyoti S., additional, Kalia, Anu, additional, Keswani, Chetan, additional, Khan, Faria, additional, Khan, Md Gulam M., additional, Khatodia, Surender, additional, Kumar, Sathiya, additional, Kumaran, Sekar, additional, LeBlanc, Jean Guy, additional, Luerce, Tessalia D., additional, Meher, Lekha C., additional, Miah, Mohammad F., additional, Misbah, Zujaja T., additional, Mishra, Bhawana, additional, Miyoshi, Anderson, additional, Mukhopadhyay, Chandra S., additional, Munshi, Anjana, additional, Mustafa, Malik G., additional, Narnoliya, Lokesh K., additional, Nasim, Mohammed, additional, Nguyen, Duy, additional, Nunes, Ricardo, additional, Padikasan, Indra A., additional, Parveen, Sajida, additional, Patade, Vikas Y., additional, Paul Khurana, S.M., additional, Pinto, Anne C., additional, Pothineni, Venkata R., additional, Rathinam, Raja, additional, Ram, Ratul M., additional, Rocha, Clarissa S., additional, Samuleev, Pavel, additional, Sangwan, Neelam S., additional, Sangwan, Rajender S., additional, Sathasivam, Ramaraj, additional, Shaheen, Kanwal, additional, Shanmugam, Hemaiswarya, additional, Sharma, Manju, additional, Sharma, S.P., additional, Sharma, Vandana, additional, Silva, Wanderson M., additional, Singh, Harikesh B., additional, Singh, Surya P., additional, Subramaniyan, Govindaraju, additional, Sudhakar, Natesan, additional, Tanveer, Tehreem, additional, Tripathi, Ruchi, additional, Tripathi, Sandhya, additional, Trofimova, Daria, additional, Waqar, Kinza, additional, Zahid, Muhammad A., additional, Zaidi, Najam-us-Sahar S., additional, and Zhou, Ting, additional

Published
2018
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37. Use of genetically modified lactic acid bacteria and bifidobacteria as live delivery vectors for human and animal health

Author

Romina Levit, Naima G. Cortes-Perez, Alejandra de Moreno de Leblanc, Jade Loiseau, Anne Aucouturier, Philippe Langella, Jean Guy LeBlanc, and Luis G. Bermúdez-Humarán

Subjects
Microbiology (medical), Vaccines, Infectious Diseases, Lactobacillales, Genetic Vectors, Gastroenterology, Animals, Humans, Bifidobacterium, Microbiology, Gastrointestinal Microbiome
Abstract

There is now strong evidence to support the interest in using lactic acid bacteria (LAB)in particular, strains of lactococci and lactobacilli, as well as bifidobacteria, for the development of new live vectors for human and animal health purposes. LAB are Gram-positive bacteria that have been used for millennia in the production of fermented foods. In addition, numerous studies have shown that genetically modified LAB and bifodobacteria can induce a systemic and mucosal immune response against certain antigens when administered mucosally. They are therefore good candidates for the development of new mucosal delivery strategies and are attractive alternatives to vaccines based on attenuated pathogenic bacteria whose use presents health risks. This article reviews the most recent research and advances in the use of LAB and bifidobacteria as live delivery vectors for human and animal health.

Published
2022

41. List of Contributors

Author

Abreu, Sandra, primary, Akal, Ceren, additional, Alavi, Farhad, additional, Aoi, Wataru, additional, Aziz, Monowar, additional, Bagwe, Siddhi M., additional, Benatar, Jocelyne R., additional, Bergholdt, Helle Kirstine Mørup, additional, Bhullar, Sukhwinder K., additional, Bourlieu, Claire, additional, Brück, Wolfram M., additional, Buttar, Harpal S., additional, Clifton, Peter, additional, da Silva Miglioranza, Lucia H., additional, De Bourdeaudhuij, Ilse, additional, de Moreno de LeBlanc, Alejandra, additional, De Pelsmaeker, Sara, additional, De Steur, Hans, additional, de Vries, Ronald P., additional, Deci, Eda, additional, Dichi, Isaias, additional, Ellervik, Christina, additional, Emam-Djomeh, Zahra, additional, Fontecha, Javier, additional, Galli, Claudio, additional, Garrido, Daniel, additional, Gellynck, Xavier, additional, Girard, Christiane L., additional, Graulet, Benoît, additional, Grosso, Giuseppe, additional, Hansen, Laura W., additional, Haraldsdottir, Alfheidur, additional, Hellgren, Lars I., additional, Horowitz, Michael, additional, Hsieh, Ying-Hsin, additional, Iwasa, Masayo, additional, Juárez, Manuela, additional, Kapaj, Ana, additional, Kapila, Rajeev, additional, Kapila, Suman, additional, Kaur, Ginpreet, additional, Kumar, Naresh, additional, Lagast, Sofie, additional, Lecomte, Manon, additional, Li, Alina, additional, Li, Jie, additional, Liu, Simin, additional, Lovozoy, Marcell A.B., additional, Machin, Daniel R., additional, Méndez Utz, Virginia E., additional, Michalski, Marie-Caroline, additional, Mohammadian, Mehdi, additional, Nero, Luís A., additional, Nestel, Paul, additional, Neyestani, Tirang R., additional, Nikooyeh, Bahareh, additional, Nordby, Pernille, additional, Nordestgaard, Børge Grønne, additional, Ozturkoglu-Budak, Sebnem, additional, Perdigón, Gabriela, additional, Perin, Luana M., additional, Prince, Jose M., additional, Raghavendra, Midathala, additional, Rayner, Christopher K., additional, Risé, Patrizia, additional, Salami, Maryam, additional, Scavuzzi, Bruna M., additional, Schouteten, Joachim Jietse, additional, Sgarbieri, Valdemiro C., additional, Sharma, Rohit, additional, Simão, Andréa N.C., additional, Singal, Hari R., additional, Song, Yan, additional, Sulaiman, Irshad M., additional, Tanaka, Hirofumi, additional, Thomson, Pamela, additional, Tokas, Jayanti, additional, Torfadottir, Johanna E., additional, Turkmen, Nazli, additional, Varbo, Anette, additional, Wang, Ping, additional, Watson, Linda E., additional, Wiley, Andrea S., additional, and Wu, Tongzhi, additional

Published
2017
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43. Streptomyces genus as a source of probiotics and its potential for its use in health

Author

S. Cuozzo, A. de Moreno de LeBlanc, J.G. LeBlanc, N. Hoffmann, and G.R. Tortella

Subjects
Probiotics, Microbiota, Animals, Microbiology, Streptomyces, Gastrointestinal Microbiome, Anti-Bacterial Agents
Abstract

The effect of a probiotic on gut microbiota depends not only on the species of microorganism but specifically on the strain. In human beings, as in other animals, specific probiotics have been associated with numerous beneficial properties, which include weight modulation (gain or loss), immune modulation, and prevention of many disorders such as lactose intolerance, cardiovascular diseases, and antibiotic-associated diarrhoea. Streptomyces are an essential group of soil bacteria in the Actinomycetes family. They are related to producing a wide range of secondary metabolites known for their beneficial effects on human health. However, according to the human microbiome analysis, a lower prevalence of Streptomyces genus exists than in other non-human microbiomes. This difference can be associated with current lifestyles. In this article, we review the benefits associated with different compounds produced by Streptomyces, with a particular focus on the production of exopolysaccharides, antibiotics, and other secondary metabolites and the potential innovative use of Streptomyces spp. as probiotics.

Published
2022

45. Thiamine-producing lactic acid bacteria and their potential use in the prevention of neurodegenerative diseases

Author

María del Milagro Teran, Graciela Savoy de Giori, Jean Guy LeBlanc, and Alejandra de Moreno de LeBlanc

Subjects
Vitamin, 0303 health sciences, 030306 microbiology, Neurotoxicity, food and beverages, General Medicine, medicine.disease, Applied Microbiology and Biotechnology, Neuroprotection, Lactic acid, 03 medical and health sciences, chemistry.chemical_compound, Biochemistry, chemistry, Amprolium, medicine, Extracellular, Thiamine, human activities, Intracellular, 030304 developmental biology, Biotechnology
Abstract

Thiamine or vitamin B1, an essential micronutrient mainly involved in energy production, has a beneficial impact on the nervous system, and its deficiency can be associated with the development and progression of neurodegenerative diseases. The aim of this work was to select thiamine-producing lactic acid bacteria (LAB) and study their physiological effects using neuron cell cultures. In this study, 23 LAB able to produce thiamine were identified by growth in thiamine-free synthetic medium. Intra- and extracellular thiamine concentrations were determined using a microbiological method and results confirmed by HPLC techniques. A wide variation in vitamin production was found showing that this property was not only species specific but also a strain-dependent trait. Five of these strains were pre-selected for their capacity to produce higher concentrations of thiamine. Only the pre-treatment with the intracellular extract of Lactiplantibacillus (L.) plantarum CRL 1905 increased significantly neuronal survival in N2a cells' model of neurotoxicity (MPP+) with thiamine deficiency conditions (amprolium). Furthermore, amprolium-resistant variants of CRL 1905 were isolated by exposition of the strain to increasing concentrations of this toxic thiamine analogue. The variant A9 was able to increase more than 2 times the intracellular thiamine production of the original strain. A9 bacterial extract significantly prevented neuronal cell death and the increase of IL-6. The amprolium-resistant strain A9 showed a modulating and neuroprotective effect in an in vitro model of neurotoxicity constituting a potential bio-strategy to counteract thiamine deficiencies and thus prevent or treat neurodegenerative diseases. KEY POINTS: • LAB can produce thiamine in a species- and strain-dependant manner. • L. plantarum CRL 1905 significantly reduce MPP+-induced neurotoxicity in N2a cells. • Amprolium-resistant strain A9 has neuroprotective effect and prevents IL-6 increase.

Published
2021

46. The ability of Riboflavin-overproducing Lactiplantibacillus plantarum strains to survive under gastrointestinal conditions

Author

Ministerio de Ciencia, Innovación y Universidades (España), Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo, European Cooperation in Science and Technology, Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Mohedano Bonillo, Mari Luz [0000-0001-6748-9443], Vignolo, Graciela [0000-0003-2368-9050], De Moreno de LeBlanc, A. [0000-0003-0352-374X], Leblanc, Jean Guy [0000-0002-4634-8630], Aznar, Rosa [0000-0002-8761-8887], López, Paloma [0000-0001-8755-8952], Hernández-Alcántara, Annel M., Pardo, S., Mohedano Bonillo, Mari Luz, Vignolo, Graciela, De Moreno de LeBlanc, A., Leblanc, Jean Guy, Aznar, Rosa, López García, Paloma, Ministerio de Ciencia, Innovación y Universidades (España), Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo, European Cooperation in Science and Technology, Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Mohedano Bonillo, Mari Luz [0000-0001-6748-9443], Vignolo, Graciela [0000-0003-2368-9050], De Moreno de LeBlanc, A. [0000-0003-0352-374X], Leblanc, Jean Guy [0000-0002-4634-8630], Aznar, Rosa [0000-0002-8761-8887], López, Paloma [0000-0001-8755-8952], Hernández-Alcántara, Annel M., Pardo, S., Mohedano Bonillo, Mari Luz, Vignolo, Graciela, De Moreno de LeBlanc, A., Leblanc, Jean Guy, Aznar, Rosa, and López García, Paloma

Abstract

Riboflavin, vitamin B2, is essential for humans and has to be obtained from the diet. Some lactic acid bacteria (LAB) produce this vitamin, and they can be used for in-situ fortification of foods. This could be an alternative to supplementation with chemically synthesized vitamin, to palliate riboflavin deficiencies in specific groups of people. Moreover, if the producing LAB could survive in the gastrointestinal stress (GIT) they could be added as probiotics in this environment. In the present study we tested two riboflavin-overproducing Lactiplantibacillus plantarum strains (M5MA1-B2 and M9MG6-B2), spontaneous mutants of LAB isolated from chicha, a traditional Andean beverage. These two LAB, and also their isogenic strains M5MA1-B2[pRCR12] and M9MG6-B2[pRCR12], expressing the mCherry protein from the pRCR12 plasmid, were evaluated in vitro under simulated GIT conditions. Among other, specifically developed protein fluorescence assays were used. The four LAB showed similar levels of adhesion (>6.0%) to Caco-2 cells, higher than that of the probiotic Lacticaseibacillus rhamnosus GG strain (4.51%). Thus, LAB biofilm formation was assessed in the labeled cells by intracellular mCherry fluorescence and in the unlabeled parental strains by crystal violet staining. Both methods detected the formation of consistent biofilms by the L. plantarum strains. The quantification of mCherry fluorescence was also used to analyze LAB auto-aggregation properties. High levels of auto-aggregation were detected for both M5MA1-B2[pRCR12] and M9MG6-B2[pRCR12]. Survival of LAB included in a commercial cereal-based food matrix (Incaparina) under GIT conditions was also evaluated. The four LAB were resistant in vitro to the stomach and intestinal stresses, and proliferated in this environment, indicating a protective and nutritional effect of the Incaparina on the bacteria. Also, M9MG6-B2 survival in the presence or absence of Incaparina was evaluated in vivo in a BALB/c mouse model. The adm

Published
2020

47. Milk fermented by Lactobacillus casei CRL431 administered as an immune adjuvant in models of breast cancer and metastasis under chemotherapy

Author

A. de Moreno de LeBlanc, D. Pérez Visñuk, V. E. Méndez Utz, and Gabriela Perdigón

Subjects
0303 health sciences, Chemotherapy, 030306 microbiology, business.industry, medicine.medical_treatment, General Medicine, Immunopotentiator, medicine.disease, Applied Microbiology and Biotechnology, Metastasis, Capecitabine, 03 medical and health sciences, Cytokine, Immune system, Breast cancer, medicine, Mucositis, Cancer research, business, 030304 developmental biology, Biotechnology, medicine.drug
Abstract

Chemotherapy is the most common treatment for breast cancer and its metastasis; however, it affects the patients' quality of life. Previously, it was demonstrated that milk fermented by Lactobacillus casei CRL431 (probiotic fermented milk (PFM)) exerted benefits against breast cancer metastasis by modulating the immune response in a mouse model. The aim of this work was to evaluate PFM administration on the side effects of capecitabine and on its anti-tumour/anti-metastatic effects. In vitro, 4T1 breast cancer cells were treated with capecitabine in the presence of immune cells' conditioned media from mice administered with PFM. Cell viability was evaluated by MTT assay. In vivo, BALB/c mice (healthy, bearing breast cancer or with potential metastasis) were treated or not with capecitabine and administered with PFM. Blood cell counts, intestinal damages, lung histology and serum cytokines were evaluated. Results showed that capecitabine's toxicity on 4T1 cells was improved by the immune cells from mice that received PFM when the lower dose of capecitabine was evaluated. PFM reduced capecitabine side effects in all the mouse models and decreased intestinal mucositis and mortality. PFM administration to mice under chemotherapy maintained the anti-cancer/anti-metastasis effect of capecitabine with similar or decreased values for serum IL-10 and TNF-α and decreased IL-6, a cytokine related to poor prognosis in advanced cancer patients. In addition, PFM by itself reduced metastasis without side effects and improved the host's immune response. PFM has a potential to be administered as an immune adjuvant in patients under chemotherapy without affecting the treatment. KEY POINTS: • Milk fermented by L. casei CRL431 (PFM) diminished capecitabine side effects. • Capecitabine's toxicity on 4T1 cells was improved by the PFM-stimulated immune cells. • PFM maintained anti-cancer/anti-metastasis effect of capecitabine in mouse models. Graphical abstract.

Published
2020

50. Contributors

Author

Abdolghaffari, Amir Hossein, primary, Abdollahi, Mohammad, additional, Ahanchian, Hamid, additional, Ahmad, Farah N., additional, Akbarzadeh, Fariborz, additional, Alighieri, Giovanni, additional, Amini, Amir, additional, Anadón, Arturo, additional, Anania, Caterina, additional, Annibale, Bruno, additional, Arena, Mattia Pia, additional, Arena, Angela, additional, Arés, Irma, additional, Argyri, Anthoula A., additional, Aslim, Belma, additional, Aydaş, Selcen Babaoğlu, additional, Azimi, Amirreza, additional, Ballesteros, Antonio O., additional, Barbosa, Joana, additional, Bastani, Parvin, additional, Bedani, Raquel, additional, Betta, Pasqua, additional, Biglu, Mohammad-Hossein, additional, Borges, Sandra, additional, Bucci, C., additional, Buriti, Flávia C.A., additional, Camacho-Ruiz, R.M., additional, Capozzi, Vittorio, additional, Catenazzi, Piero, additional, Celani, Camilla, additional, Chaluvadi, Saikiran, additional, Champagne, Claude P., additional, Chiesa, Claudio, additional, Clark, Eva H., additional, Collier, Robert J., additional, Colombo, Jacopo, additional, de Moreno de LeBlanc, Alejandra, additional, de Morais, Elisa Carvalho, additional, Dekker, M., additional, Di Venere, D., additional, Drago, Lorenzo, additional, Farnworth, Edward R., additional, Feleszko, Wojciech, additional, Fernandez-Arrojo, Lucia, additional, Fernández-López, J., additional, Finamore, Alberto, additional, Fiocco, Daniela, additional, Gatesoupe, F.J., additional, Ghasemi-Niri, Farnaz, additional, Giacchi, Valentina, additional, Golkhalkhali, Babak, additional, Gomez-Zavaglia, A., additional, Gooshe, Maziar, additional, Gundogdu, Zuhal, additional, Hanning, Irene, additional, Hashemi, Seyed Mohammad Bagher, additional, Hemalatha, Rajkumar, additional, Homayouni, Aziz, additional, Hotchkiss, Arland T., additional, Iovino, P., additional, Saad, Susana Marta Isay, additional, Jafarabadi, Mohammad Asghari, additional, Jafari, Seyed Ali, additional, Jamaluddin, Rosita, additional, Jeong, Ji-Kang, additional, Jirillo, Felicita, additional, Jirillo, Emilio, additional, Jones, Rheinallt M., additional, Kaur, Baljinder, additional, Kaur, Gaganjot, additional, Keshtiban, Ata K., additional, Khalili, Mohammad, additional, Khalili, Leyla, additional, Khalili, Leila, additional, Kirmiz, Nina, additional, Kumar, Manoj, additional, Lahner, Edith, additional, Lavermicocca, P., additional, LeBlanc, Jean Guy, additional, Likotrafiti, Eleni, additional, Lim, Ying-Jye, additional, Lingbeck, Jody, additional, López, Paloma, additional, Mohedano, Mª Luz, additional, Magrone, Thea, additional, Mahdavi, Reza, additional, Maleki, Davood, additional, Mallah, Fatemeh, additional, Marathe, Shreesh J., additional, Marotta, Francesco, additional, Martínez, María Aránzazu, additional, Martinez-Augustin, O., additional, Martínez-Larrañaga, María Rosa, additional, Mehrabany, Elnaz Vaghef, additional, Mills, David A., additional, Stover, Mitchel Graham, additional, Mobili, P., additional, Mohammad, Diya, additional, Mohammad-Alizadeh-Charandabi, Sakineh, additional, Redzwan, S. Mohd, additional, Monedero, Vicente, additional, Moreno Villares, Jose M., additional, Moreno-Vilet, L., additional, Morrow, Lee E., additional, Motoori, Masaaki, additional, Murthy, Jayasimha N., additional, Nácher-Vázquez, Montserrat, additional, Nagpal, Ravinder, additional, Nielsen, Dennis Sandris, additional, Nikniaz, Hossein, additional, Nikniaz, Leila, additional, Nikniaz, Zeinab, additional, Notararigo, Sara, additional, Nunes, Vânia dos Santos, additional, Orel, Rok, additional, Osman, Ali, additional, Ouwehand, Arthur C., additional, Pacifico, Lucia, additional, Panagou, Efstathios Z., additional, Park, Kun-Young, additional, Payahoo, Laleh, additional, Peluso, Ilaria, additional, Pérez-Alvarez, J.A., additional, Pérez-Ramos, Adrian, additional, Plou, Francisco J., additional, Poorbaghi, Seyedeh Leila, additional, Portales-Pérez, D.P., additional, Quigley, Eamonn M.M., additional, Ranjbar, Fatemeh, additional, Reberšak, Lea Vodušek, additional, Rhoades, Jonathan, additional, Ricke, Steven C., additional, Rodriguez-Colinas, Barbara, additional, Rodríguez-Díaz, Jesús, additional, Romano, N., additional, Russo, Pasquale, additional, Russo, F., additional, Ruszczyński, Marek, additional, Saad, Susana M.I., additional, de Medina, F. Sánchez, additional, Santonicola, A., additional, Sayas-Barberá, M.E., additional, Sciacca, Pietro, additional, Scorrano, Antonio, additional, Sendra, E., additional, Sepehrimanesh, Masood, additional, Serafini, Mauro, additional, Shek, Lynette Pei-Chi, additional, Shokrvash, Behjat, additional, Sisto, A., additional, Sivieri, Katia, additional, Skalkam, Maria Lena, additional, Soh, Shu-E, additional, Spano, Giuseppe, additional, Sugimura, Keijiro, additional, Tanaka, Koji, additional, Tassou, Chrysoula C., additional, Teixeira, Paula, additional, Tennilä, Julia, additional, Toscano, Marco, additional, Tripathi, Alok S., additional, Tymczyszyn, E., additional, Valerio, F., additional, van Zanten, Gabriella, additional, Villas Boas, Paulo José Fortes, additional, Wachholz, Patrick Alexander, additional, Watson, Ronald Ross, additional, Wiese, Maria, additional, Yadav, Hariom, additional, Yam, Kit L., additional, Yano, Masahiko, additional, Zeng, Hongliang, additional, Zhang, Yi, additional, Zheng, Baodong, additional, Ziyadi, Somayeh, additional, and Zuppa, Antonio Alberto, additional

Published
2016
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