Limosilactobacillus fermentum CECT5716: Mechanisms and Therapeutic Insights

This work was supported by the Junta de Andalucía (CTS 164) and Instituto de Salud Carlos III (PI19/01058) with funds from the European Union.M.J. Rodríguez-Sojo is a predoctoral fellow from University of Granada (“Programa de Doctorado en Biomedicina”); A.J. Ruiz-Malagón is a predoctoral fellow from Formación de Profesorado Universitario Program (“Programa de Doctorado en Medicina Clínica y Salud Pública”), and A. Rodríguez-Nogales is a postdoctoral fellow of Instituto de Salud Carlos III (Miguel Servet Program).Probiotics microorganisms exert their health-associated activities through some of the following general actions: competitive exclusion, enhancement of intestinal barrier function, production of bacteriocins, improvement of altered microbiota, and modulation of the immune response. Among them, Limosilactobacillus fermentum CECT5716 has become one of the most promising probiotics and it has been described to possess potential beneficial effects on inflammatory processes and immunological alterations. Different studies, preclinical and clinical trials, have evidenced its anti-inflammatory and immunomodulatory properties and elucidated the precise mechanisms of action involved in its beneficial effects. Therefore, the aim of this review is to provide an updated overview of the effect on host health, mechanisms, and future therapeutic approaches.Junta de Andalucia CTS 164Instituto de Salud Carlos III European Commission PI19/01058European Commissio

Compact Embedded Wireless Sensor-Based Monitoring of Concrete Curing

This work presents the design, construction and testing of a new embedded sensor system for monitoring concrete curing. A specific mote has been implemented to withstand the aggressive environment without affecting the measured variables. The system also includes a real-time monitoring application operating from a remote computer placed in a central location. The testing was done in two phases: the first in the laboratory, to validate the functional requirements of the developed devices; and the second on civil works to evaluate the functional features of the devices, such as range, robustness and flexibility. The devices were successfully implemented resulting in a low cost, highly reliable, compact and non-destructive solution.Fondos FEDER IDI-2010044

Tigecycline reduces tumorigenesis in colorectal cancer via inhibition of cell proliferation and modulation of immune response

Junta de Andalucía (CTS 164)Instituto de Salud Carlos III (Spain)Fondo Europeo de Desarrollo Regional (FEDER)European Union, through the research grants PI18/00826, P18-RT-4930, PI0206–2016, PIE16/00045 and PI19/01058Spanish Ministry of Science and Innovation (MCIN/AEI/ 10.13039/501100011033/FEDER)RTI2018–101309-BC22Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963Spanish Ministry of Science and Innovation (“Programa de Doctorado: Medicina Clínica y Salud Pública” B12.56.1).Instituto de Salud Carlos III (FI17/00176)Junta de Andalucía (P18-RT-4930)University of GranadaCIBER-EHD is funded by the Instituto de Salud Carlos II

Silk fibroin nanoparticles enhance quercetin immunomodulatory properties in DSS-induced mouse colitis

This work has been supported from the European Commission ERDF/FEDER Operational Programme `Murcia' CCI N. 2007ES161PO001 (Project No. 14-20/20), the Junta de Andalucia (CTS164), Instituto de Salud Carlos III (PI19/01058) and the Spanish MINECO (Ref. CTQ201787708-R). P.D.-E. is a postdoctoral from Junta de Andalucia (European Commission FEDER); A.J.R.-M and L.H.-G. are predoctoral fellows from University of Granada ("Programa de Doctorado: Medicina Clinica y Salud Publica"); A.A.L.-P's research contract was supported by the ERDF/FEDER Operational Programme `Murcia' CCI N 2007ES161PO001 (Project No. 14-20/20); A.R.-N. is a postdoctoral fellow of Instituto de Salud Carlos III (Miguel Servet Program); T.V. is a postdoctoral fellow from Instituto de Investigación Biosanitaria de Granada.Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disorder affecting the gastrointes-tinal tract. The pharmacological treatments used currently for its treatment lack efficacy, so new therapeutic strategies should be developed. In this context, flavonoids loaded in biopolymeric nanoparticles can be considered as novel promising candidates. The aim of the present study was to evaluate the intestinal anti-inflammatory effects of quercetin when is administered loaded in silk fibroin nanoparticles (QSFN) in the dextran sulphate sodium experimental model of mouse colitis, which displays some similarities to human IBD. Previously characterized quercetin-loaded silk fibroin nanoparticles (QSFN). QSFN showed a reversible aggre-gation profile induced by the acidification of the solution but did not affect the loaded quercetin. Daily administration of QSFN significantly reduced disease activity index values compared to the control colitic group. This beneficial effect was not only corroborated by the histological examination of the colonic specimens but also the improvement of the colonic expression of the different proinflammatory cytokines (Tnf-alpha, Il-1 beta, Il-6, Mcp-1, Icam-1, Nlrp3 and iNOS). Therefore, these data suggest that QSFN could be a promising alternative to current treatments as a drug delivery system for IBD treatment.European Commission ERDF/FEDER Operational Programme `Murcia' CCI 2007ES161PO001- 14-20/20Junta de Andalucia CTS164Instituto de Salud Carlos III European Commission PI19/01058Spanish MINECO CTQ201787708-RERDF/FEDER Operational Programme 'Murcia' CCI 2007ES161PO001- 14-20/2

The Antioxidant Properties of Lavandula multifida Extract Contribute to Its Beneficial Effects in High-Fat Diet-Induced Obesity in Mice

Obesity is a worldwide public health problem whose prevalence rate has increased steadily over the last few years. Therefore, it is urgent to improve the management of obesity and its comorbidities, and plant-based treatments are receiving increasing attention worldwide. In this regard, the present study aimed to investigate a well-characterized extract of Lavandula multifida (LME) in an experimental model of obesity in mice and explore the underlying mechanisms. Interestingly, the daily administration of LME reduced weight gain as well as improved insulin sensitivity and glucose tolerance. Additionally, LME ameliorated the inflammatory state in both liver and adipose tissue by decreasing the expression of various proinflammatory mediators (Il-6, Tnf-a, Il-1b, Jnk-1, Ppara, Pparg, and Ampk) and prevented increased gut permeability by regulating the expression of mucins (Muc-1, Muc-2, and Muc-3) and proteins implicated in epithelial barrier integrity maintenance (Ocln, Tjp1, and Tff-3). In addition, LME showed the ability to reduce oxidative stress by inhibiting nitrite production on macrophages and lipid peroxidation. These results suggest that LME may represent a promising complementary approach for the management of obesity and its comorbidities.Junta de Andalucía (CTS 164), by the Instituto de Salud Carlos III (ISCIII) (PI19.01058)Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R)European Commission (FEDER/ERDF). The CIBEREHDInstituto de Salud Carlos II

The Antioxidant Activity of Thymus serpyllum Extract Protects against the Inflammatory State and Modulates Gut Dysbiosis in Diet-Induced Obesity in Mice

Nowadays, there is an increasing interest in alternative therapies in the treatment of metabolic syndrome that combine efficacy and safety profiles. Therefore, this study aimed to evaluate the effect of an extract of Thymus serpyllum, containing rosmarinic acid, on high-fat diet (HFD)- induced obesity mice, highlighting the impact of its antioxidant activity on the inflammatory status and gut dysbiosis. The extract was administered daily (50, 100 and 150 mg/kg) in HFD-fed mice. The treatment reduced body weight gain, glucose and lipid metabolic profiles. Moreover, the extract ameliorated the inflammatory status, with the c-Jun N-terminal kinases (JUNK) pathway being involved, and showed a significant antioxidant effect by the reduction of radical scavenging activity and the mitigation of lipid peroxidation. Moreover, the extract was able to modulate the altered gut microbiota, restoring microbial richness and diversity, and augmenting the counts of short-chain fatty acid producing bacteria, which have been associated with the maintenance of gut permeability and weight regulation. In conclusion, the antioxidant activity of Thymus serpyllum extract displayed a positive impact on obesity and its metabolic alterations, also reducing systemic inflammation. These effects may be mediated by modulation of the gut microbiota.Junta de Andalucia CTS 164Instituto de Salud Carlos III European Commission PI19.01058Spanish Government AGL201567995-C3-3-REuropean CommissionInstituto de Salud Carlos II

The Antioxidant Properties of Salvia verbenaca Extract Contribute to Its Intestinal Antiinflammatory Effects in Experimental Colitis in Rats

La enfermedad inflamatoria intestinal (EII) es una inflamación gastrointestinal crónica con fluctuaciones de síntomas impredecibles. Si bien no existe una cura eficaz para la EII, varios tratamientos tienen como objetivo controlar los síntomas y mejorar la calidad de vida de las personas afectadas. En los últimos años, ha habido un interés creciente en los beneficios potenciales de ciertas plantas y hierbas naturales en el tratamiento de la EII. En este sentido, este estudio tuvo como objetivo evaluar los efectos inmunomoduladores y antiinflamatorios de un extracto bien caracterizado de Salvia verbenaca (S. verbenaca) en un modelo experimental de colitis en ratas. Curiosamente, la administración diaria de S. verbenaca (10 y 25 mg/kg) alivió eficazmente los síntomas de la colitis, como lo demuestra la reducción de la relación peso/longitud y el daño colónico. Además, redujo los marcadores de estrés oxidativo (MPO y GSH), disminuyó la expresión de citocinas proinflamatorias (Il-6, Il-12a, Il-1β, Il-23, Icam-1, Mcp-1, Cinc-1) y conservó la integridad de la barrera intestinal (Villin, Muc-2, Muc-3). Estos efectos sugieren que el extracto de S. verbenaca podría representar un potencial candidato complementario para tratar los trastornos gastrointestinales. Sus acciones beneficiosas pueden estar relacionadas con sus propiedades antioxidantes, así como con la regulación negativa de la respuesta inmune, lo que puede resultar en la mejora de la barrera epitelial del intestino.Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammation with unpredictable symptom fluctuations. While there is no effective cure for IBD, various treatments aim to manage symptoms and improve the quality of life for affected individuals. In recent years, there has been growing interest in the potential benefits of certain natural plants and herbs in the management of IBD. In this regard, this study aimed to evaluate the immunomodulatory and anti-inflammatory effects of a well-characterized extract of Salvia verbenaca (S. verbenaca) in an experimental model of colitis in rats. Interestingly, the daily administration of S. verbenaca (10 and 25 mg/kg) effectively alleviated colitis symptoms, as evidenced by reduced weight/length ratio and colonic damage. Moreover, it reduced oxidative stress markers (MPO and GSH), decreased pro-inflammatory cytokine expression (Il-6, Il-12a, Il-1β, Il-23, Icam-1, Mcp-1, Cinc-1), and preserved the integrity of the intestinal barrier (Villin, Muc-2, Muc-3). These effects suggest S. verbenaca extract could represent a potential complementary candidate to treat gastrointestinal disorders. Its beneficial actions can be related to its antioxidant properties as well as the downregulation of the immune response, which can result in the improvement in the intestine epithelial barrier.Junta de Andalucia (AGR-6826)Junta de Andalucia (CTS-164)Ministerio de Economía y Competitividad (SAF2011-29648)Instituto de Salud Carlos III (pFIS (FI20/00159)Instituo de Saud Carlos III (Miguel Servet CP22/00153

The Prebiotic Effects of an Extract with Antioxidant Properties from Morus alba L. Contribute to Ameliorate High-Fat Diet-Induced Obesity in Mice

Obesity is a global health issue, in which modifications in gut microbiota composition have a key role. Different therapeutic strategies are being developed in combination with diet and exercise, including the use of plant extracts, such as those obtained from Morus alba L. leaves. Recent studies have revealed their anti-inflammatory and antioxidant properties. The aim of the present work was to evaluate whether the beneficial effects of M. alba L. leaf extract in high-fat diet-induced obesity in mice is correlated with its impact on gut microbiota. The extract reduced body weight gain and attenuated lipid accumulation, as well as increased glucose sensitivity. These effects were associated with an amelioration of the obesity-associated inflammatory status, most probably due to the described antioxidant properties of the extract. Moreover, M. alba L. leaf extract mitigated gut dysbiosis, which was evidenced by the restoration of the Firmicutes/Bacteroidota ratio and the decrease in plasma lipopolysaccharide (LPS) levels. Specifically, the extract administration reduced Alistipes and increased Faecalibaculum abundance, these effects being correlated with the beneficial effects exerted by the extract on the obesity-associated inflammation. In conclusion, anti-obesogenic effects of M. alba L. leaf extract may be mediated through the amelioration of gut dysbiosis.Junta de Andalucia CTS 164Instituto de Salud Carlos III PI19.01058Spanish Government AGL2015-67995-C3-3-Rperational Programme of the Region of Murcia (CCI) 2007ES161PO001 14-20/20European CommissionInstituto de Salud Carlos IIIi-pFIS, Instituto de Salud Carlos III; Programa de Doctorado BiomedicinapFIS, Instituto de Salud Carlos III; Programa de Doctorado Nutricio

Beneficial Effects of Limosilactobacillus fermentum in the DCA Experimental Model of Irritable Bowel Syndrome in Rats

Limosilactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, has reported beneficial effects on different gastrointestinal disorders. Moreover, it has shown its ability to restore altered immune responses, in association with microbiome modulation in different pathological conditions. Therefore, our aim was to assess the effects of a Limosilacbacillus fermentum CECT5716 in a rat experimental model of irritable bowel syndrome (IBS) that resembles human IBS. The experimental IBS was induced by deoxycholic acid (DCA) in rats and then, Limosilactobacillus fermentum CECT5716 (109 CFU/day/rat) was administered. Behavioral studies, hyperalgesia and intestinal hypersensitivity determinations were performed and the impact of the probiotic on the inflammatory and intestinal barrier integrity was evaluated. Additionally, the gut microbiota composition was analyzed. Limosilactobacillus fermentum CECT5716 attenuated the anxiety-like behavior as well as the visceral hypersensitivity and referred pain. Moreover, this probiotic ameliorated the gut inflammatory status, re-establishing the altered intestinal permeability, reducing the mast cell degranulation and re-establishing the gut dysbiosis in experimental IBS. Therefore, our results suggest a potential use of Limosilactobacillus fermentum CECT5716 in clinical practice for the management of IBS patients.Junta de Andalucia A-CTS-447-UGR18 CTS 164Instituto de Salud Carlos IIIEuropean Commission PI19/01058 PI20/0144

Intestinal mesenchymal cells regulate immune responses and promote epithelial regeneration in vitro and in dextran sulfate sodium-induced experimental colitis in mice

This work was funded by the Junta de Andalucia (CTS 164) and by the Instituto de Salud Carlos III (Spain) and Fondo Europeo de Desarrollo Regional (FEDER), from the European Union, through the research grants PI18/00826, PI0206-2016 and PI19/01058. L.H-G and A.J.R-M are predoctoral fellows funded by the Spanish Ministry of Science and Innovation ("Programa de Doctorado: Medicina Clinica y Salud Publica" B12.56.1). J.A.M-T is a predoctoral fellow from the Instituto de Salud Carlos III (FI17/00176). P.A is supported by the Consejeria de Salud, Junta de Andalucia through the contract "Nicolas Monardes" (C-0013-2018). A. R-N is a postdoctoral fellow from the Instituto de Salud Carlos III (Miguel Servet program [CP19/00191]). CIBER-EHD is funded by the Instituto de Salud Carlos III.We would like to express our gratitude to Dr E. Aksoy and Dr L. Medrano Gonzalez (William Harvey Research Institute, Queen Mary University of London, London, UK) for providing us the cell line NCM356. Additionally, we thank Juan N. Moliz, Ana Santos and Mohamed Tassi of the Centre for Scientific Instrumentation (CIC, University of Granada) for their technical guidance and assistance.Aim Disruption of the intestinal mucosal tolerance, that is, the immunological unresponsiveness to innocuous food antigens and the commensal microbiota, in the colon is associated with several chronic diseases including inflammatory bowel disease (IBD). Understanding the mechanisms responsible for intestinal mucosal tolerance has potential translational value for its therapy and management. Human intestinal mesenchymal cells (iMCs) play important roles in colonic mucosal tolerance, but further studies on their tissue regenerative and immunomodulatory capacities are necessary in order to fully understand their function in health and disease. Methods In this study, we have isolated and analysed the capacity of human iMCs to promote wound healing and modulate immune responses in vitro and in vivo, using the dextran sulfate sodium (DSS)-induced colitis model. Results Cultured iMCs were CD45(-)CD73(+)CD90(+)CD105(+) and accelerated the wound closure in a normal colon mucosa (NCM) 356 human epithelial cell wound healing assay. Furthermore, iMCs blocked the LPS-mediated induction of TNF-alpha in THP-1 macrophages and inhibited the proliferation of peripheral blood mononuclear cells, partly through the induction of indoleamine-2,3-dioxygenase. In DSS colitic mice, iMCs administration reduced the disease activity index and ameliorated intestinal tissue damage and permeability. Furthermore, iMCs reduced intestinal inflammation, evidenced by a decreased mRNA expression of pro-inflammatory cytokines, reduced IL-1 beta secretion by intestinal explants and inhibited colonic iNOS protein expression. Conclusions Our data show that human iMCs isolated from the noninflamed intestine possess tissue-regenerative and immunomodulatory capacities that could potentially be harnessed/restored in order to reduce IBD severity.Junta de Andalucia CTS 164Instituto de Salud Carlos III European CommissionFondo Europeo de Desarrollo Regional (FEDER), from the European Union PI18/00826 PI0206-2016 PI19/01058Spanish Ministry of Science and Innovation ("Programa de Doctorado: Medicina Clinica y Salud Publica") B12.56.1Junta de Andalucia C-0013-2018Miguel Servet program CP19/00191Instituto de Salud Carlos III European Commissio