Publication: Actividad antimicrobiana de ácidos grasos Omega 3 frente a bacterias patógenas orales en un modelo subgingival multiespecie validado de biofilm in vitro
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2019
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Abstract
Antecedentes y Objetivos: Investigaciones previas han demostrado la capacidad antimicrobiana de los extractos de ácidos grasos poliinsaturados (PUFAs) n-3 de cadena larga frente a varios patógenos periodontales en estado planctónico. Sin embargo, la mayor parte de las bacterias en la naturaleza, y por ende en la cavidad oral, se encuentran organizadas en biofilms. No obstante, la literatura existente sobre el efecto de estos extractos en los patógenos periodontales organizados en modelos de biofilm in vitro es todavía escasa, o se trata de modelos de biofilms mono-especie. Por esta razón, el objetivo de este estudio es analizar de manera independiente la capacidad antibacteriana de dos extractos de ácidos grasos n-3 de cadena larga: ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA), en un modelo validado de biofilm multi-especie formado in vitro, constituido por Streptococcus oralis, Actinomyces naeslundii, Veillonela parvula y los patógenos periodontales Fusobacterium nucleatum, Porphyromonas gingivalis y Aggregatibacter actinomycetemcomitans.
Material y Métodos: Teniendo en cuenta las MBCs y las MICs observadas de las seis especies bacterianas implicadas, se utilizó un modelo validado de biofilm multi-especie in vitro, para evaluar la capacidad antibacteriana de los extractos de EPA y DHA (100 µM), frente a las especies bacterianas organizadas en biofilm, tras 60 segundos de exposición. Para ello, se realizó el recuento de las bacterias -expresadas como unidades formadoras de colonias por mililitro (UFC/mL)- mediante la técnica reacción cuantitativa en cadena de la polimerasa en tiempo real (qPCR, por sus siglas en inglés). Además, la vitalidad celular de los biofilms fue analizadas por microscopía de barrido laser confocal (CLSM, por sus siglas en inglés). Con relación al análisis estadístico, la variable dependiente seleccionada -para valorar el efecto antibacteriana de DHA y EPA de manera independiente- fue el número de UFC/mL viables presentes en el biofilm. Para contrastar la normalidad de la distribución de los datos estos fueron sometidos al test de Shapiro-Wilk. El efecto de cada extracto (variables independientes) y su interacción con las variables dependientes, se evaluó mediante el test paramétrico ANOVA y las correcciones de Bonferroni para comparaciones múltiples. Los datos se expresaron como medias ± desviación estándar y como el porcentaje medio de inhibición. Los resultados se consideraron estadísticamente significativos con p<0,05.
Resultados: Con respecto a la capacidad antibacteriana, los extractos de DHA y EPA (100 µM) provocaron reducciones estadísticamente significativas en las UFC/mL viables de todas las bacterias en el modelo de biofilm in vitro S. oralis, A. naeslundii, V. parvula, F. nucleatum, P. gingivalis y A. actinomycetemcomitans- tras 60 segundos de exposición. Alcanzándose reducciones de hasta tres órdenes de magnitud con respecto al control negativo (PBS) en el caso de DHA y de dos (A. naeslundii, F. nucleatum, P. gingivalis) o uno (S. oralis, V. parvula, A. actinomycetemcomitans) en el caso de EPA.
Conclusiones: Los extractos de EPA y DHA presentan capacidad antimicrobiana frente a seis especies bacterianas (S. oralis, A. naeslundii, V. parvula, y los patógenos periodontales F. nucleatum, P. gingivalis y A. actinomycetemcomitans y) organizadas en biofilm, de manera significativa frente a todas ellas.
Background and Objectives: Previous studies have reported the antimicrobial effects of long chain omega-3 polyunsaturated fatty acids extracts against periodontal pathogens in planktonic state. Nonetheless, most of the bacteria in nature, and thus in the oral cavity, are organized in biofilm state. Notwithstanding, the existing literature on the effect of these extracts on periodontal pathogens organized in in vitro biofilm models is still limited or is linked to mono-species biofilm models. Accordingly, the aim of this study is to analyze, in an independent approach, the antimicrobial capacity of long chain omega-3 fatty acids extracts: docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in a validated multi-species in vitro biofilm model, constituted by Streptococcus oralis, Actinomyces naeslundii, Veillonela parvula, and the periodontal pathogens Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Material and Methods: Based on the MBCs and the MICs of the six bacterial species involved, a validated in vitro biofilm model was used to evaluate the antibacterial activity of EPA and DHA extracts (100 µM) against bacteria organized in biofilms, after 60 seconds of exposure. With this objective, bacterial counts were performed using the real-time quantitative polymerase chain reaction (qPCR) technique. Besides, the cellular vitality of the biofilms was assessed by confocal laser scanning microscopy (CLSM). In regard to the statistical analysis, the dependent variable selected -to analyze the antibacterial effect of EPA and DHA in an independent approach- was the viable CFU/mL of the six bacterial species present on the biofilm. To check the normality of the data distribution, the Shapiro-Wilk test was performed. The effect of each extract (independent variables) and its interplay with the dependent variables was assessed by the parametric ANOVA test and Bonferroni´s corrections for multiple comparisons. Data were expressed as means ± standard deviation and as mean percentage of inhibition. The results were considered statistically significant at p<0.05. 21 Results: According to the antibacterial capacity, EPA and DHA extracts (100 µM) triggered significant reductions on viable CFU/mL of all bacteria included in the biofilm in vitro model - S. oralis, A. naeslundii, V. parvula, F. nucleatum, P. gingivalis and A. actinomycetemcomitans- after 60 seconds of exposure. Achieving reductions up to three orders of magnitude with regard to the negative control (PBS) in the case of DHA and of two (A. naeslundii, F. nucleatum, P. gingivalis) or one (S. oralis, V. parvula, A. actinomycetemcomitans) in the case of EPA. Conclusions: Natural extracts of EPA and DHA display antibacterial capacity against six bacterial species (S. oralis, A. naeslundii, V. parvula, and the periodontal pathogens F. nucleatum, P. gingivalis and A. actinomycetemcomitans) organized in biofilm, in a statistically significant way against all of them.
Background and Objectives: Previous studies have reported the antimicrobial effects of long chain omega-3 polyunsaturated fatty acids extracts against periodontal pathogens in planktonic state. Nonetheless, most of the bacteria in nature, and thus in the oral cavity, are organized in biofilm state. Notwithstanding, the existing literature on the effect of these extracts on periodontal pathogens organized in in vitro biofilm models is still limited or is linked to mono-species biofilm models. Accordingly, the aim of this study is to analyze, in an independent approach, the antimicrobial capacity of long chain omega-3 fatty acids extracts: docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in a validated multi-species in vitro biofilm model, constituted by Streptococcus oralis, Actinomyces naeslundii, Veillonela parvula, and the periodontal pathogens Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Material and Methods: Based on the MBCs and the MICs of the six bacterial species involved, a validated in vitro biofilm model was used to evaluate the antibacterial activity of EPA and DHA extracts (100 µM) against bacteria organized in biofilms, after 60 seconds of exposure. With this objective, bacterial counts were performed using the real-time quantitative polymerase chain reaction (qPCR) technique. Besides, the cellular vitality of the biofilms was assessed by confocal laser scanning microscopy (CLSM). In regard to the statistical analysis, the dependent variable selected -to analyze the antibacterial effect of EPA and DHA in an independent approach- was the viable CFU/mL of the six bacterial species present on the biofilm. To check the normality of the data distribution, the Shapiro-Wilk test was performed. The effect of each extract (independent variables) and its interplay with the dependent variables was assessed by the parametric ANOVA test and Bonferroni´s corrections for multiple comparisons. Data were expressed as means ± standard deviation and as mean percentage of inhibition. The results were considered statistically significant at p<0.05. 21 Results: According to the antibacterial capacity, EPA and DHA extracts (100 µM) triggered significant reductions on viable CFU/mL of all bacteria included in the biofilm in vitro model - S. oralis, A. naeslundii, V. parvula, F. nucleatum, P. gingivalis and A. actinomycetemcomitans- after 60 seconds of exposure. Achieving reductions up to three orders of magnitude with regard to the negative control (PBS) in the case of DHA and of two (A. naeslundii, F. nucleatum, P. gingivalis) or one (S. oralis, V. parvula, A. actinomycetemcomitans) in the case of EPA. Conclusions: Natural extracts of EPA and DHA display antibacterial capacity against six bacterial species (S. oralis, A. naeslundii, V. parvula, and the periodontal pathogens F. nucleatum, P. gingivalis and A. actinomycetemcomitans) organized in biofilm, in a statistically significant way against all of them.
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