Clinical trial, phase IV, randomized, double-blind, controlled, in children aged 12 to 35 months, of the vaccine against seasonal influenza to estimate efficacy against influenza and other respiratory infections - VIGIRA

开始日期2019-09-27

申办/合作机构

Fisabio Foundation

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2024-12-31·Journal of Oral Microbiology

The effects of nitrate on the oral microbiome: a systematic review investigating prebiotic potential

Review

作者: Moran, Siobhan P ; Henriquez, Fiona L ; Rosier, Bob T ; Burleigh, Mia C

BackgroundNitrate (NO₃^-) has been suggested as a prebiotic for oral health. Evidence indicates dietary nitrate and nitrate supplements can increase the proportion of bacterial genera associated with positive oral health whilst reducing bacteria implicated in oral disease(s). In contrast, chlorhexidine-containing mouthwashes, which are commonly used to treat oral infections, promote dysbiosis of the natural microflora and may induce antimicrobial resistance.MethodsA systematic review of the literature was undertaken, surrounding the effects of nitrate on the oral microbiota.ResultsOverall, n = 12 in vivo and in vitro studies found acute and chronic nitrate exposure increased (representatives of) health-associated Neisseria and Rothia (67% and 58% of studies, respectively) whilst reducing periodontal disease-associated Prevotella (33%). Additionally, caries-associated Veillonella and Streptococcus decreased (25% for both genera). Nitrate also altered oral microbiome metabolism, causing an increase in pH levels (n = 5), which is beneficial to limit caries development. Secondary findings highlighted the benefits of nitrate for systemic health (n = 5).ConclusionsMore clinical trials are required to confirm the impact of nitrate on oral communities. However, these findings support the hypothesis that nitrate could be used as an oral health prebiotic. Future studies should investigate whether chlorhexidine-containing mouthwashes could be replaced or complemented by a nitrate-rich diet or nitrate supplementation.

2024-12-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

A disturbed metabolite-GPCR axis is associated with microbial dysbiosis in IBD patients: Potential role of GPR109A in macrophages

Article

作者: Cosín-Roger, Jesús ; Ortiz-Masiá, Dolores ; Macias-Ceja, Dulce Carolina ; Calatayud, Sara ; Cejudo-Garcés, Andrea ; Bauset, Cristina ; Buetas, Elena ; Navarro-Vicente, Francisco ; Esplugues, Juan Vicente ; Barrachina, María Dolores ; Mira, Álex ; Carda-Diéguez, Miguel ; Seco-Cervera, Marta

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by disrupted immune function. Indeed, gut microbiota dysbiosis and metabolomic profile alterations, are hallmarks of IBD. In this scenario, metabolite-sensing G-protein coupled receptors (GPCRs), involved in several biological processes, have emerged as pivotal players in the pathophysiology of IBD. The aim of this study was to characterize the axis microbiota-metabolite-GPCR in intestinal surgical resections from IBD patients. Results showed that UC patients had a lower microbiota richness and bacterial load, with a higher proportion of the genus Cellulosimicrobium and a reduced proportion of Escherichia, whereas CD patients showed a decreased abundance of Enterococcus. Furthermore, metabolomic analysis revealed alterations in carboxylic acids, fatty acids, and amino acids in UC and CD samples. These patients also exhibited upregulated expression of most metabolite-sensing GPCRs analysed, which positively correlated with pro-inflammatory and pro-fibrotic markers. The role of GPR109A was studied in depth and increased expression of this receptor was detected in epithelial cells and cells from lamina propria, including CD68+ macrophages, in IBD patients. The treatment with β-hydroxybutyrate increased gene expression of GPR109A, CD86, IL1B and NOS2 in U937-derived macrophages. Besides, when GPR109A was transiently silenced, the mRNA expression and secretion of IL-1β, IL-6 and TNF-α were impaired in M1 macrophages. Finally, the secretome from siGPR109A M1 macrophages reduced the gene and protein expression of COL1A1 and COL3A1 in intestinal fibroblasts. A better understanding of metabolite-sensing GPCRs, such as GPR109A, could establish their potential as therapeutic targets for managing IBD.

2024-06-01·Biofilm

Multimodal evaluation of drug antibacterial activity reveals cinnamaldehyde analog anti-biofilm effects against Haemophilus influenzae

Article

作者: Burgui, Saioa ; Lázaro-Díez, María ; Monteserín, María ; Arroyo-Urea, Eva M ; Buetas, Elena ; González-Paredes, Ana ; Garmendia, Junkal ; Hernández-Cruz, Tania M ; Blanco-Cabra, Núria ; Asensio-López, Javier ; Sorzabal-Bellido, Ioritz ; Ortiz de Solórzano, Carlos ; Torrents, Eduard

Biofilm formation by the pathobiont Haemophilus influenzae is associated with human nasopharynx colonization, otitis media in children, and chronic respiratory infections in adults suffering from chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). β-lactam and quinolone antibiotics are commonly used to treat these infections. However, considering the resistance of biofilm-resident bacteria to antibiotic-mediated killing, the use of antibiotics may be insufficient and require being replaced or complemented with novel strategies. Moreover, unlike the standard minimal inhibitory concentration assay used to assess antibacterial activity against planktonic cells, standardization of methods to evaluate anti-biofilm drug activity is limited. In this work, we detail a panel of protocols for systematic analysis of drug antimicrobial effect on bacterial biofilms, customized to evaluate drug effects against H. influenzae biofilms. Testing of two cinnamaldehyde analogs, (E)-trans-2-nonenal and (E)-3-decen-2-one, demonstrated their effectiveness in both H. influenzae inhibition of biofilm formation and eradication or preformed biofilms. Assay complementarity allowed quantifying the dynamics and extent of the inhibitory effects, also observed for ampicillin resistant clinical strains forming biofilms refractory to this antibiotic. Moreover, cinnamaldehyde analog encapsulation into poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles allowed drug vehiculization while maintaining efficacy. Overall, we demonstrate the usefulness of cinnamaldehyde analogs against H. influenzae biofilms, present a test panel that can be easily adapted to a wide range of pathogens and drugs, and highlight the benefits of drug nanoencapsulation towards safe controlled release.

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