La microbiota oral: una revisión de literatura para la actualización de profesionales en odontología. Parte I

In recent decades, a body of literature examining the relationships between oral health and general health has rapidly developed. However, the biological mechanisms involved in explaining such relationships have not been fully described. Recent evidence has suggested that these relationships could be partially explained by the composition and interaction of the microbiome/microbiota between local and systemic body sites. For instance, it has been suggested that intestinal microbiota could have effects on non-communicable diseases, such as diabetes or cardiovascular diseases. The objective of this study is to explore current evidence of the link between oral and systemic diseases, to discuss whether oral microbiome/microbiota could represent an unexplored biological pathway partially explaining those relationships. A non-systematic review of the literature was carried out using keyword searches in Pubmed from February to May 2019. The ultimate goal was to present recent scientific evidence to update the general knowledge on this topic to professionals in dentistry. This review is divided in two parts for journal publication; however, it is intended to be used as one piece. In this first part, we will summarize the conceptual background of oral microbiome/microbiota, we will describe the main methods used in microbiology to characterize oral organisms, and will present the main composition of bacteria in oral microbiome/microbiota. The second part highlights the main evidence regarding the biological plausibility that links oral microbiome and systemic diseases and we will conclude with some future research recommendations. Taking into account the role of oral microbiota in the development of systemic diseases could change the main paradigm of how oral health is currently conceptualized by dental professionals.En las últimas décadas, se ha acumulado evidencia sobre las relaciones existentes entre la salud oral y la salud general. Sin embargo, los mecanismos biológicos implicados en la explicación de tales relaciones no se han logrado describir completamente. Investigaciones recientes han sugerido que parte de esta relación se podría explicar por la composición e interacción del microbioma o la microbiota a nivel local y sistémico. Por ejemplo, la evidencia ha mostrado que la microbiota intestinal parece tener efectos sobre enfermedades crónicas no transmisibles, como la diabetes o las enfermedades cardiovaculares. En esta revisión bibliográfica, se han seleccionado algunos estudios que han tratado de hipotetizar que el microbioma y la microbiota oral podrían representar un mecanismo biológico poco explorado que podría explicar parcialmente las relaciones que se han observado entre condiciones orales y enfermedades sistémicas. El objetivo de esta revisión es analizar la evidencia actual que explica los posibles mecanismos que desempeñan un papel en las asociaciones entre la salud oral y la salud sistémica. La hipótesis discutida es que el microbioma y microbiota oral podría ser un mecanismo biológico que podría explicar parcialmente las influencias de las enfermedades orales sobre la salud general. Se realizó una revisión no sistemática de la literatura entre febrero y mayo del 2019 en la plataforma PubMed. El objetivo final es presentar evidencia científica reciente para actualizar el conocimiento general sobre este tema para los profesionales en odontología. Esta revisión se presenta en dos partes por consideraciones editoriales, sin embargo, la intención es que ambas sean leídas como una sola pieza. En esta primera parte, se presentarán las bases conceptuales, se describirán los principales métodos utilizados en microbiología para caracterizar los organismos orales y se mencionará la composición descrita en la literatura de los principales microorganismos presentes en la microbiota oral. En la segunda parte, se sintetizará la evidencia principal sobre la plausibilidad biológica que vincula el microbioma oral y las enfermedades sistémicas, y concluiremos con algunas recomendaciones de investigación futuras. Esta perspectiva podría cambiar el paradigma principal de cómo se conceptualiza actualmente la salud oral por parte de los profesionales en odontología.UCR::Vicerrectoría de Docencia::Salud::Facultad de Odontologí

Porphyromonas spp. have an extensive host range in ill and healthy individuals and an unexpected environmental distribution: a systematic review and meta-analysis

Studies on the anaerobic bacteria Porphyromonas, mainly focused on P. gingivalis, have revealed new bacterial structures, metabolic pathways, and physiologic functionalities. Porphyromonas are mainly described as being associated with mammals and involved in chronic oral infections and secondary pathologies such as cancers or neurodegenerative diseases. In this review, we collected and analyzed information regarding Porphyromonas isolation sites and associated conditions and showed that Porphyromonas are detected in numerous pristine and anthropic environments and that their host range appears wider than previously believed, including aquatic animals, arthropods, and birds, even if their predominant hosts remain humans, pets, and farm animals. Our analyses also revealed their presence in multiple organs and in a substantial proportion of healthy contexts. Overall, the growing numbers of microbiota studies have allowed unprecedented advances in the understanding of Porphyromonas ecology but raise questions regarding their phylogenic assignment. In conclusion, this systematic and meta-analysis provides an overview of current knowledge regarding Porphyromonas ecological distribution and encourages additional research to fill the knowledge gaps to better understand their environmental distribution and inter- and intra-species transmission.Universidad de Costa Rica, Vicerrectoría de InvestigaciónInstitut Français d'Amérique CentraleUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Síndrome inflamatorio multisistémico asociado a COVID-19 en pacientes pediátricos

Introduction: since the first cases of COVID-19 appeared, it has spread around the world dangerously fast. At the beginning, it was thought that it mainly affected adults and the elderly, but in early May 2020, cases of children began to be described, who after being infected, developed a multisystemic inflammatory syndrome, causing death in some cases. Objective: to describe the multisystemic inflammatory syndrome associated with COVID-19 in children, for which a total of 17 bibliographies were consulted. Development: this syndrome is a recent pathology with little incidence, but it evolves in a torpid way. It manifests itself with several symptoms and signs, among the most frequent are the fever and gastrointestinal manifestations.Conclusions: without a proven treatment yet, detecting patients in the early stages of the disease is the key to avoiding future complications.Introducción: desde la aparición de los primeros casos de COVID-19, esta se ha propagado por todo el mundo a una velocidad vertiginosa. En su inicio se pensaba que afectaba mayormente a adultos y ancianos, pero a principios de mayo del 2020 se comienzan a describir casos de niños que luego del contagiado, desarrollaban un síndrome inflamatorio multisistémico, llegando en algunos casos hasta la muerte. Objetivo: describir el síndrome inflamatorio multisistémico asociado a la COVID-19 en niños, para ello se consultó un total de 17 bibliografías. Desarrollo: este síndrome es una patología reciente con poca incidencia, pero que evoluciona de manera tórpida. Se manifiesta con varios síntomas y signos, entre la más frecuente fiebre y manifestaciones gastrointestinales. Conclusiones: sin un tratamiento aún comprobado, el detectar a los pacientes en los primeros estadios de la enfermedad constituye la clave para evitar futuras complicaciones

Multisystemic inflammatory syndrome associated with COVID-19 in pediatric patients

Introduction: since the first cases of COVID-19 appeared, it has spread around the world dangerously fast. At the beginning, it was thought that it mainly affected adults and the elderly, but in early May 2020, cases of children began to be described, who after being infected, developed a multisystemic inflammatory syndrome, causing death in some cases. Objective: to describe the multisystemic inflammatory syndrome associated with COVID-19 in children, for which a total of 17 bibliographies were consulted. Development: this syndrome is a recent pathology with little incidence, but it evolves in a torpid way. It manifests itself with several symptoms and signs, among the most frequent are the fever and gastrointestinal manifestations. Conclusions: without a proven treatment yet, detecting patients in the early stages of the disease is the key to avoiding future complications

Emergence of an Outbreak-Associated Clostridium difficile Variant with Increased Virulence

The prevalence of Clostridium difficile infections has increased due to the emergence of epidemic variants from diverse genetic lineages. Here we describe the emergence of a novel variant during an outbreak in a Costa Rican hospital that was associated with severe clinical presentations. This C. difficile variant elicited higher white blood cell counts and caused disease in younger patients than did other strains isolated during the outbreak. Furthermore, it had a recurrence rate, a 30-day attributable disease rate, and disease severity as great as those of the epidemic strain NAP1. Pulsed-field gel electrophoresis genotyping indicated that the outbreak strains belong to a previously undescribed variant, designated NAPCR1. Whole-genome sequencing and ribotyping indicated that the NAPCR1 variant belongs to C. difficile ribotype 012 and sequence type 54, as does the reference strain 630. NAPCR1 strains are resistant to fluoroquinolones due to a mutation in gyrA, and they possess an 18-bp deletion in tcdC that is characteristic of the epidemic, evolutionarily distinct, C. difficile NAP1 variant. NAPCR1 genomes contain 10% more predicted genes than strain 630, most of which are of hypothetical function and are present on phages and other mobile genetic elements. The increased virulence of NAPCR1 was confirmed by mortality rates in the hamster model and strong inflammatory responses induced by bacteria-free supernatants in the murine ligated loop model. However, NAPCR1 strains do not synthesize toxin A and toxin B at levels comparable to those in NAP1 strains. Our results suggest that the pathogenic potential of this emerging C. difficile variant is due to the acquisition of hypothetical functions associated with laterally acquired DNA.Universidad de Costa Rica/[803-B1-654]/UCR/Costa RicaUniversidad de Costa Rica/[803-B1-602]/UCR/Costa RicaConsejo Nacional de Ciencia y Tecnología/[FV-0004-13]/CONICIT/Costa Rica. Fondo gestionado a través de FORINVESPrograma de Cooperación Internacional/[130621650]/FA0/BrasilWellcome Trust/[098051}//Reino UnidoWellcome Trust/[086418]//Reino UnidoWellcome Trust/[098051]//Reino UnidoUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Étude bioinformatique des génomes de Porphyromonas

Bacteria of Bacteroidetes phylum, Bacteroidia class, are amongst the more important in gastrointestimal microbiota, either human or from other mammals. The mouth, digestive tube entry, is an environment with varied anatomic sites, each having a particular microbiota with different composition. The union between gingiva and teeth, the gingival sulcus, is a site for biofilm (dental plaque) formation and accumulation. Porphyromonas gingivalis, a bacterium from this phylum, can modulate the inmune system and produce an oral biofilm desequilibrium called dysbiosis. This triggers the formation of a periodontal pocket, a pathological deepening of the gingival sulcus, and the emergence of periodontitis. Other Porphyromonas species are also associated to periodontitis, mainly in canids. P. gingivalis populations are panmictic and their genomes are highly plastic. Bioinformatics can help to identify the causes of this genomic mosaicity, to study Porphyromonas virulence factors in order to explain why some species are pathogens and other are commensal, and to describe the dysbiosis linked to periodontitis. P. gingivalis comparative genomics showed a correlation between the number of contigs in draft genomes and genomic repeats, mainly insertion sequences. We resequenced, reassembled and reannotated three reference strains of this bacterium that already had complete published genomes, using long-read sequencing. We showed that misassemblies were present in the three published genomes, and we corrected them. A pangenome study of the three strains showed that the core genome is preponderant. The species plasticity might be related more to the genome organization than to different coding capacities. A subpart of th core genome, with genes having a nucleotidic identity percentage lower than the majority (variable core genome), is interesting for explaining the phenotypic differences of bacteria. We analysed the repertoire of a virulence factor, fimbriae, adhesion structures, in the Porphyromonas genus to link the loci to phylogeny and pathogenicity of its species. Finally, we described the dysbiosis occuring with periodontitis, analysing gingival microbiota of patients having the illness and healthy individuals. Preponderant genera in both states are highlighted. With this work, we demonstrate the importance of biocuration and its added value for genomic and bioinformatic studies in general. Only with this slow and arduous work, the answers to biological questions will be relevant.Les bactéries du phylum Bacteroidetes, classe Bacteroidia, sont parmi les plus importantes dans microbiotes gastrointestinaux des humains et d'autres mammifères. La bouche, entrée du tube digestif, est un environnement avec des sites anatomiques variés, auxquels s'associent des microbiotes de composition différente. L'union de la gencive et des dents, le sillon gingivo-dentaire ou sulcus, est un site de dépôt d'un biofilm complexe appelé plaque dentaire. Une bactérie de ce phylum, Porphyromonas gingivalis, est capable de perturber le système immunitaire humain et de produire un déséquilibre du biofilm oral également nommée dysbiose. Ceci déclenche la formation de la poche parodontale, un creusement pathologique du sulcus, et l'apparition de la parodontite. D’autres espèces du genre Porphyromonas sont également associées à la parodontite notamment chez les canidés. Les populations de P. gingivalis sont panmictiques et la plasticité de leurs génomes importante. La bioinformatique peut aider à identifier les causes de la mosaïcité des génomes de cette bactérie, à étudier les facteurs de virulence au niveau du genre bactérien pour expliquer l'existence d'espèces pathogènes et d'autres commensales et à décrire la dysbiose liée à la parodontite. La génomique comparative de P. gingivalis a démontré une corrélation entre le nombre de contigs dans les génomes draft de cette espèce et les répétitions génomiques, notamment des séquences d'insertion. Nous avons re-séquencé, re-assemblé et re-annoté trois souches de référence de cette bactérie qui avaient des génomes complets, en utilisant un séquençage en long-read. Nous avons mis en évidence des erreurs d'assemblage sur les trois génomes publiés, que nous avons corrigé. Une étude du pangénome de ces trois souches montre un génome core important. La plasticité de l'espèce serait donc plus dans l'organisation du génome que dans les différentes capacités de codage. Une sous partie du génome core, dont les gènes ont un pourcentage d'identité nucléotidique plus faible que la plupart (génome core variant) est intéressante pour expliquer les différences phénotypiques de ces bactéries. Nous avons étudié la répartition d'un facteur de virulence, les fimbriae, structures d'adhésion, au sein du genre Porphyromonas et lié les loci à la phylogénie et au caractère pathogène des espèces. Finalement, une description de la dysbiose qui a lieu lors d'une parodontite est faite par une analyse du microbiote de patients atteints de parodontite et d'individus sains. Les genres prépondérants lors des deux états sont mis en évidence. Au cours de ces travaux, nous montrons l'importance de la biocuration et sa valeur ajoutée dans les travaux de génomique et bioinformatique en général. Seulement en faisant ce travail lent et lourd de biocuration, les réponses apportées aux questions biologiques seront pertinentes

Bioinformatic study of Porphyromonas genomes

Les bactéries du phylum Bacteroidetes, classe Bacteroidia, sont parmi les plus importantes dans microbiotes gastrointestinaux des humains et d'autres mammifères. La bouche, entrée du tube digestif, est un environnement avec des sites anatomiques variés, auxquels s'associent des microbiotes de composition différente. L'union de la gencive et des dents, le sillon gingivo-dentaire ou sulcus, est un site de dépôt d'un biofilm complexe appelé plaque dentaire. Une bactérie de ce phylum, Porphyromonas gingivalis, est capable de perturber le système immunitaire humain et de produire un déséquilibre du biofilm oral également nommée dysbiose. Ceci déclenche la formation de la poche parodontale, un creusement pathologique du sulcus, et l'apparition de la parodontite. D’autres espèces du genre Porphyromonas sont également associées à la parodontite notamment chez les canidés. Les populations de P. gingivalis sont panmictiques et la plasticité de leurs génomes importante. La bioinformatique peut aider à identifier les causes de la mosaïcité des génomes de cette bactérie, à étudier les facteurs de virulence au niveau du genre bactérien pour expliquer l'existence d'espèces pathogènes et d'autres commensales et à décrire la dysbiose liée à la parodontite. La génomique comparative de P. gingivalis a démontré une corrélation entre le nombre de contigs dans les génomes draft de cette espèce et les répétitions génomiques, notamment des séquences d'insertion. Nous avons re-séquencé, re-assemblé et re-annoté trois souches de référence de cette bactérie qui avaient des génomes complets, en utilisant un séquençage en long-read. Nous avons mis en évidence des erreurs d'assemblage sur les trois génomes publiés, que nous avons corrigé. Une étude du pangénome de ces trois souches montre un génome core important. La plasticité de l'espèce serait donc plus dans l'organisation du génome que dans les différentes capacités de codage. Une sous partie du génome core, dont les gènes ont un pourcentage d'identité nucléotidique plus faible que la plupart (génome core variant) est intéressante pour expliquer les différences phénotypiques de ces bactéries. Nous avons étudié la répartition d'un facteur de virulence, les fimbriae, structures d'adhésion, au sein du genre Porphyromonas et lié les loci à la phylogénie et au caractère pathogène des espèces. Finalement, une description de la dysbiose qui a lieu lors d'une parodontite est faite par une analyse du microbiote de patients atteints de parodontite et d'individus sains. Les genres prépondérants lors des deux états sont mis en évidence. Au cours de ces travaux, nous montrons l'importance de la biocuration et sa valeur ajoutée dans les travaux de génomique et bioinformatique en général. Seulement en faisant ce travail lent et lourd de biocuration, les réponses apportées aux questions biologiques seront pertinentes.Bacteria of Bacteroidetes phylum, Bacteroidia class, are amongst the more important in gastrointestimal microbiota, either human or from other mammals. The mouth, digestive tube entry, is an environment with varied anatomic sites, each having a particular microbiota with different composition. The union between gingiva and teeth, the gingival sulcus, is a site for biofilm (dental plaque) formation and accumulation. Porphyromonas gingivalis, a bacterium from this phylum, can modulate the inmune system and produce an oral biofilm desequilibrium called dysbiosis. This triggers the formation of a periodontal pocket, a pathological deepening of the gingival sulcus, and the emergence of periodontitis. Other Porphyromonas species are also associated to periodontitis, mainly in canids. P. gingivalis populations are panmictic and their genomes are highly plastic. Bioinformatics can help to identify the causes of this genomic mosaicity, to study Porphyromonas virulence factors in order to explain why some species are pathogens and other are commensal, and to describe the dysbiosis linked to periodontitis. P. gingivalis comparative genomics showed a correlation between the number of contigs in draft genomes and genomic repeats, mainly insertion sequences. We resequenced, reassembled and reannotated three reference strains of this bacterium that already had complete published genomes, using long-read sequencing. We showed that misassemblies were present in the three published genomes, and we corrected them. A pangenome study of the three strains showed that the core genome is preponderant. The species plasticity might be related more to the genome organization than to different coding capacities. A subpart of th core genome, with genes having a nucleotidic identity percentage lower than the majority (variable core genome), is interesting for explaining the phenotypic differences of bacteria. We analysed the repertoire of a virulence factor, fimbriae, adhesion structures, in the Porphyromonas genus to link the loci to phylogeny and pathogenicity of its species. Finally, we described the dysbiosis occuring with periodontitis, analysing gingival microbiota of patients having the illness and healthy individuals. Preponderant genera in both states are highlighted. With this work, we demonstrate the importance of biocuration and its added value for genomic and bioinformatic studies in general. Only with this slow and arduous work, the answers to biological questions will be relevant

The Oral Microbiota: A Literature Review for Updating Professionals in Dentistry. Part I

In recent decades, a body of literature examining the relationships between oral health and general health has rapidly developed. However, the biological mechanisms involved in explaining such relationships have not been fully described. Recent evidence has suggested that these relationships could be partially explained by the composition and interaction of the microbiome/microbiota between local and systemic body sites. For instance, it has been suggested that intestinal microbiota could have effects on non-communicable diseases, such as diabetes or cardiovascular diseases. The objective of this study is to explore current evidence of the link between oral and systemic diseases, to discuss whether oral microbiome/microbiota could represent an unexplored biological pathway partially explaining those relationships. A non-systematic review of the literature was carried out using keyword searches in Pubmed from February to May 2019. The ultimate goal was to present recent scientific evidence to update the general knowledge on this topic to professionals in dentistry. This review is divided in two parts for journal publication; however, it is intended to be used as one piece. In this first part, we will summarize the conceptual background of oral microbiome/microbiota, we will describe the main methods used in microbiology to characterize oral organisms, and will present the main composition of bacteria in oral microbiome/microbiota. The second part highlights the main evidence regarding the biological plausibility that links oral microbiome and systemic diseases and we will conclude with some future research recommendations. Taking into account the role of oral microbiota in the development of systemic diseases could change the main paradigm of how oral health is currently conceptualized by dental professionals.En las últimas décadas, se ha acumulado evidencia sobre las relaciones existentes entre la salud oral y la salud general. Sin embargo, los mecanismos biológicos implicados en la explicación de tales relaciones no se han logrado describir completamente. Investigaciones recientes han sugerido que parte de esta relación se podría explicar por la composición e interacción del microbioma o la microbiota a nivel local y sistémico. Por ejemplo, la evidencia ha mostrado que la microbiota intestinal parece tener efectos sobre enfermedades crónicas no transmisibles, como la diabetes o las enfermedades cardiovaculares. En esta revisión bibliográfica, se han seleccionado algunos estudios que han tratado de hipotetizar que el microbioma y la microbiota oral podrían representar un mecanismo biológico poco explorado que podría explicar parcialmente las relaciones que se han observado entre condiciones orales y enfermedades sistémicas. El objetivo de esta revisión es analizar la evidencia actual que explica los posibles mecanismos que desempeñan un papel en las asociaciones entre la salud oral y la salud sistémica. La hipótesis discutida es que el microbioma y microbiota oral podría ser un mecanismo biológico que podría explicar parcialmente las influencias de las enfermedades orales sobre la salud general. Se realizó una revisión no sistemática de la literatura entre febrero y mayo del 2019 en la plataforma PubMed. El objetivo final es presentar evidencia científica reciente para actualizar el conocimiento general sobre este tema para los profesionales en odontología. Esta revisión se presenta en dos partes por consideraciones editoriales, sin embargo, la intención es que ambas sean leídas como una sola pieza. En esta primera parte, se presentarán las bases conceptuales, se describirán los principales métodos utilizados en microbiología para caracterizar los organismos orales y se mencionará la composición descrita en la literatura de los principales microorganismos presentes en la microbiota oral. En la segunda parte, se sintetizará la evidencia principal sobre la plausibilidad biológica que vincula el microbioma oral y las enfermedades sistémicas, y concluiremos con algunas recomendaciones de investigación futuras. Esta perspectiva podría cambiar el paradigma principal de cómo se conceptualiza actualmente la salud oral por parte de los profesionales en odontología

The Oral Microbiota: a Literature Review for Updating Professionals in Dentistry-Part II

In the first part of this literature review, published in October 2019 in this journal, we summarized the conceptual background of the oral microbiota, and the main methods used in microbiology to characterize oral organisms. We also presented the most studied bacteria species in the oral microbiota. In this second part, we will discuss the evidence regarding the biological plausibility linking the oral microbiota dysbiosis and systemic diseases, as well as the main factors and mechanisms suspected in this association.En la primera parte de esta revisión de literatura, publicada en esta revista en octubre de 2019, se resumieron los antecedentes conceptuales de la microbiota oral y describieron los principales métodos utilizados en microbiología para caracterizar los microorganismos orales. Asimismo, se presentaron las especies bacterianas mejor estudiadas de la microbiota oral. En esta segunda parte, se explorará la plausibilidad biológica que vincularía la disbiosis de la microbiota oral y las enfermedades sistémicas, así como las características que podrían influenciar la composición de la microbiota oral.UCR::Vicerrectoría de Docencia::Salud::Facultad de Odontologí

Maternal Linoleic Acid Overconsumption Alters Offspring Gut and Adipose Tissue Homeostasis in Young but Not Older Adult Rats.

Maternal -6 polyunsaturated fatty acids (PUFA) consumption during gestation and lactation can predispose offspring to the development of metabolic diseases such as obesity later in life. However, the mechanisms underlying the potential programming effect of -6 PUFA upon offspring physiology are not yet all established. Herein, we investigated the effects of maternal and weaning linoleic acid (LA)-rich diet interactions on gut intestinal and adipose tissue physiology in young (3-month-old) and older (6-month-old) adult offspring. Pregnant rats were fed a control diet (2% LA) or an LA-rich diet (12% LA) during gestation and lactation. At weaning, offspring were either maintained on the maternal diet or fed the other diet for 3 or 6 months. At 3 months of age, the maternal LA-diet favored low-grade inflammation and greater adiposity, while at 6 months of age, offspring intestinal barrier function, adipose tissue physiology and hepatic conjugated linoleic acids were strongly influenced by the weaning diet. The maternal LA-diet impacted offspring cecal microbiota diversity and composition at 3 months of age, but had only few remnant effects upon cecal microbiota composition at 6 months of age. Our study suggests that perinatal exposure to high LA levels induces a differential metabolic response to weaning diet exposure in adult life. This programming effect of a maternal LA-diet may be related to the alteration of offspring gut microbiota