Healthy human gut phageome.

The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

Isolation and Characterization of Metallosphaera Turreted Icosahedral Virus, a Founding Member of a New Family of Archaeal Viruses.

Our understanding of archaeal virus diversity and structure is just beginning to emerge. Here we describe a new archaeal virus, tentatively named Metallosphaera turreted icosahedral virus (MTIV), that was isolated from an acidic hot spring in Yellowstone National Park, USA. Two strains of the virus were identified and were found to replicate in an archaeal host species closely related to Metallosphaera yellowstonensis Each strain encodes a 9.8- to 9.9-kb linear double-stranded DNA (dsDNA) genome with large inverted terminal repeats. Each genome encodes 21 open reading frames (ORFs). The ORFs display high homology between the strains, but they are quite distinct from other known viral genes. The 70-nm-diameter virion is built on a T=28 icosahedral lattice. Both single particle cryo-electron microscopy and cryotomography reconstructions reveal an unusual structure that has 42 turret-like projections: 12 pentameric turrets positioned on the icosahedral 5-fold axes and 30 turrets with apparent hexameric symmetry positioned on the icosahedral 2-fold axes. Both the virion structural properties and the genome content support MTIV as the founding member of a new family of archaeal viruses.IMPORTANCE Many archaeal viruses are quite different from viruses infecting bacteria and eukaryotes. Initial characterization of MTIV reveals a virus distinct from other known bacterial, eukaryotic, and archaeal viruses; this finding suggests that viruses infecting Archaea are still an understudied group. As the first known virus infecting a Metallosphaera sp., MTIV provides a new system for exploring archaeal virology by examining host-virus interactions and the unique features of MTIV structure-function relationships. These studies will likely expand our understanding of virus ecology and evolution.

Viral Strain-Specific Differential Alterations in Arabidopsis Developmental Patterns.

Turnip mosaic virus (TuMV) infections affect many Arabidopsis developmental traits. This paper analyzes, at different levels, the development-related differential alterations induced by different strains of TuMV, represented by isolates UK 1 and JPN 1. The genomic sequence of JPN 1 TuMV isolate revealed highest divergence in the P1 and P3 viral cistrons, upon comparison with the UK 1 sequence. Infectious viral chimeras covering the whole viral genome uncovered the P3 cistron as a major viral determinant of development alterations, excluding the involvement of the PIPO open reading frame. However, constitutive transgenic expression of P3 in Arabidopsis did not induce developmental alterations nor modulate the strong effects induced by the transgenic RNA silencing suppressor HC-Pro from either strain. This highlights the importance of studying viral determinants within the context of actual viral infections. Transcriptomic and interactomic analyses at different stages of plant development revealed large differences in the number of genes affected by the different infections at medium infection times but no significant differences at very early times. Biological functions affected by UK 1 (the most severe strain) included mainly stress response and transport. Most cellular components affected cell-wall transport or metabolism. Hubs in the interactome were affected upon infection.

Past, present, and future of microbiome-based therapies.

Technological advances in studying the human microbiome in depth have enabled the identification of microbial signatures associated with health and disease. This confirms the crucial role of microbiota in maintaining homeostasis and the host health status. Nowadays, there are several ways to modulate the microbiota composition to effectively improve host health; therefore, the development of therapeutic treatments based on the gut microbiota is experiencing rapid growth. In this review, we summarize the influence of the gut microbiota on the development of infectious disease and cancer, which are two of the main targets of microbiome-based therapies currently being developed. We analyze the two-way interaction between the gut microbiota and traditional drugs in order to emphasize the influence of gut microbial composition on drug effectivity and treatment response. We explore the different strategies currently available for modulating this ecosystem to our benefit, ranging from 1st generation intervention strategies to more complex 2nd generation microbiome-based therapies and their regulatory framework. Lastly, we finish with a quick overview of what we believe is the future of these strategies, that is 3rd generation microbiome-based therapies developed with the use of artificial intelligence (AI) algorithms.

Gut bacteriophage dynamics during fecal microbial transplantation in subjects with metabolic syndrome.

Metabolic Syndrome (MetS) is a growing public health concern worldwide. Individuals with MetS have an increased risk for cardiovascular (CV) disease and type 2 diabetes (T2D). These diseases - in part preventable with the treatment of MetS - increase the chances of premature death and pose a great economic burden to health systems. A healthy gut microbiota is associated with a reduction in MetS, T2D, and CV disease. Treatment of MetS with fecal microbiota transplantation (FMT) can be effective, however, its success rate is intermediate and difficult to predict. Because bacteriophages significantly affect the microbiota membership and function, the aim of this pilot study was to explore the dynamics of the gut bacteriophage community after FMT in MetS subjects. We performed a longitudinal study of stool bacteriophages from healthy donors and MetS subjects before and after FMT treatment. Subjects were assigned to either a control group (self-stool transplant, n = 3) or a treatment group (healthy-donor-stool transplant; n-recipients = 6, n-donors = 5). Stool samples were collected over an 18-week period and bacteriophage-like particles were purified and sequenced. We found that FMT from healthy donors significantly alters the gut bacteriophage community. Subjects with better clinical outcome clustered closer to the heathy donor group, suggesting that throughout the treatment, their bacteriophage community was more similar to healthy donors. Finally, we identified bacteriophage groups that could explain these differences and we examined their prevalence in individuals from a larger cohort of MetS FMT trial.Trial information- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2705; NTR 2705.

The Human Gut Phage Community and Its Implications for Health and Disease.

In this review, we assess our current understanding of the role of bacteriophages infecting the human gut bacterial community in health and disease. In general, bacteriophages contribute to the structure of their microbial communities by driving host and viral diversification, bacterial evolution, and by expanding the functional diversity of ecosystems. Gut bacteriophages are an ensemble of unique and shared phages in individuals, which encompass temperate phages found predominately as prophage in gut bacteria (prophage reservoir) and lytic phages. In healthy individuals, only a small fraction of the prophage reservoir is activated and found as extracellular phages. Phage community dysbiosis is characterized by a shift in the activated prophage community or an increase of lytic phages, and has been correlated with disease, suggesting that a proper balance between lysis and lysogeny is needed to maintain health. Consequently, the concept of microbial dysbiosis might be extended to the phage component of the microbiome as well. Understanding the dynamics and mechanisms to restore balance after dysbiosis is an active area of research. The use of phage transplants to re-establish health suggests that phages can be used as disease treatment. Such advances represent milestones in our understanding of gut phages in human health and should fuel research on their role in health and disease.

Plant-made potyvirus-like particles used for log-increasing antibody sensing capacity.

Deployment of the elongated flexuous virions of Turnip mosaic virus (TuMV), a potyvirus, for peptide display on their external surface has been previously reported by us. Nonetheless, both in TuMV and other potyviruses some peptides hinder the ability of the virus to infect host plants. We found that a peptide derived from the human thrombin receptor (TR) inhibited TuMV infectivity. In an effort to get around this problem, TuMV virus-like particles (VLPs) were produced in plants by transient high-level expression of wild-type or recombinant coat protein (CP). Significant production of both recombinant and non-recombinant CP proteins was obtained from plant leaves. Assembled particles of each of these two proteins into VLPs were observed under the electron microscope. The capacity of TR-CP VLPs to log-increase the ability of TR antibody-sensing was confirmed. These results confirm that the use of VLPs is an effective way to overcome the problem of displaying infectivity-interfering peptides. This is yet another way of exploiting the use of plant-made flexuous elongated VLPs for nanobiotechnological purposes.

Type 2 Diabetes Screening Test by Means of a Pulse Oximeter.

In this paper, we propose a method for screening for the presence of type 2 diabetes by means of the signal obtained from a pulse oximeter. The screening system consists of two parts: the first analyzes the signal obtained from the pulse oximeter, and the second consists of a machine-learning module. The system consists of a front end that extracts a set of features form the pulse oximeter signal. These features are based on physiological considerations. The set of features were the input of a machine-learning algorithm that determined the class of the input sample, i.e., whether the subject had diabetes or not. The machine-learning algorithms were random forests, gradient boosting, and linear discriminant analysis as benchmark. The system was tested on a database of [Formula: see text] subjects (two samples per subject) collected from five community health centers. The mean receiver operating characteristic area found was [Formula: see text]% (median value [Formula: see text]% and range [Formula: see text]%), with a specificity =  [Formula: see text]% for a threshold that gave a sensitivity = [Formula: see text]%. We present a screening method for detecting diabetes that has a performance comparable to the glycated haemoglobin (haemoglobin A1c HbA1c) test, does not require blood extraction, and yields results in less than 5 min.

Greater allergenicity of topical ketoprofen in contact dermatitis confirmed by use.

The use of topical non-steroidal anti-inflammatory drugs (NSAIDs) is very popular in spite of their doubtful efficacy and high number of generally not serious, but preventable, adverse effects, especially photoallergy. The allergenic potential of different topical NSAIDs was determined by performing a retrospective observational study of the period 1996-2001 and comparing the cases of allergy and photoallergy with the use of each topical NSAID. The diagnoses were obtained from a review of the clinical records of patch/photopatch testing carried out in the dermatology departments of 2 public hospitals in Bizkaia (Spain). The use of the different topical NSAIDs was obtained from invoices sent to the National Health System and the Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) disproportionality estimates of the FEDRA database of the Spanish Pharmacovigilance System. A total of 139 contact reactions to topical NSAIDs were found with ketoprofen being responsible for 28% of the allergies and 82% of the contact photoallergies in spite of not being the most used topical NSAID (third in the ranking, diclofenac was the first). The ROR for ketoprofen was 3.9 (2.4-6.4) and the PRR 3.4 (2.1-5.5), thus confirming the possibility of a warning signal. The results support the need for regulatory action on topical ketoprofen.

[Consensus document on phototherapy: PUVA therapy and narrow-band UVB therapy]. / Documento de consenso sobre fototerapia: terapias PUVA y UVB de banda estrecha.

It is essential to develop a consensus document on phototherapy in order to adapt this procedure to the specific characteristics, needs and reality of our milieu. Using a review of existing literature on the subject and the experience of its own members as a reference, the Spanish Photobiology Group (GEF) of the Spanish Academy of Dermatology and Venereology (AEDV) has developed some therapeutic guidelines for the most widely used modes of phototherapy: PUVA therapy and narrow-band UVB (NBUVB) therapy. These guidelines deal with generalities about the equipment, calibration and regulation in phototherapy booths, and the concept and indications for these forms of treatment are reviewed. Recommendations are also proposed regarding patient selection, therapeutic procedures, associated pharmacological agents of interest and the prevention and management of adverse effects. The consensus document is designed as a flexible and practical instrument intended for use in daily clinical practice, aimed at optimizing the possibilities of phototherapy while reducing risks for patients and therapists.

Documento de consenso sobre fototerapia: terapias PUVA y UVB de banda estrecha / Consensus document on phototherapy: PUVA therapy and narrow-band UVB therapy

La elaboración de un documento de consenso en fototerapia resulta imprescindible en el objetivo de adaptar este procedimiento a las peculiaridades, necesidades y realidad de nuestro ámbito. Tomando como referencia la revisión de la literatura existente al respecto y la experiencia propia de sus miembros, el Grupo Español de Fotobiología (GEF) de la Academia Española de Dermatología y Venereología (AEDV) ha elaborado unas guías terapéuticas para las modalidades de fototerapia más empleadas: terapia con psoraleno y radiación ultravioleta de longitud de onda A (PUVA) y terapia con radiación ultravioleta de longitud de onda B de banda estrecha (UVB-BE). En ellas se abordan generalidades acerca del utillaje, calibración y reglamentación en las cabinas de fototerapia, se revisan el concepto y las indicaciones de estas formas de tratamiento y se proponen recomendaciones referidas a la selección de pacientes, los procedimientos terapéuticos, las asociaciones farmacológicas de interés y la prevención y manejo de los efectos adversos. El documento de consenso se concibe como un instrumento flexible y práctico destinado a su empleo en la clínica diaria con el objetivo de optimizar las posibilidades de la fototerapia reduciendo los riesgos para pacientes y terapeutas

It is essential to develop a consensus document on phototherapy in order to adapt this procedure to the specific characteristics, needs and reality of our milieu. Using a review of existing literature on the subject and the experience of its own members as a reference, the Spanish Photobiology Group (GEF) of the Spanish Academy of Dermatology and Venereology (AEDV) has developed some therapeutic guidelines for the most widely used modes of phototherapy: PUVA therapy and narrow-band UVB (NBUVB) therapy. These guidelines deal with generalities about the equipment, calibration and regulation in phototherapy booths, and the concept and indications for these forms of treatment are reviewed. Recommendations are also proposed regarding patient selection, therapeutic procedures, associated pharmacological agents of interest and the prevention and management of adverse effects. The consensus document is designed as a flexible and practical instrument intended for use in daily clinical practice, aimed at optimizing the possibilities of phototherapy while reducing risks for patients and therapists

Estudio epidemiológico de la dermatitis alérgica de contacto en España (2001) / Epidemiological study of allergic contact dermatitis in Spain (2001)

Introducción: El estudio mediante pruebas de contacto estándar es fundamental para diagnosticar y tratar cualquier paciente en el que se sospeche una dermatitis de contacto. El primer estudio estadístico con pruebas epicutáneas estándar del Grupo Español de Investigación de Dermatitis de Contacto (GEIDC) data de 1977. Veinticinco años más tarde, se realiza este estudio que tiene como objetivo valorar la prevalencia y la relevancia de las positividades a los alergenos de la serie estándar del GEIDC. Métodos: Todos los pacientes fueron estudiados mediante la serie estándar del GEIDC (29 alergenos) en 13 centros dermatológicos. Se valoraron los siguientes parámetros: sexo, edad, localización, diagnóstico, causa del eccema, positividades y relevancia total, presente y pasada. Resultados: El 55,11% de los 3.832 pacientes estudiados (2.300 mujeres y 1.532 varones) tuvieron alguna positividad en la serie estándar. Los diagnósticos más frecuentes fueron la dermatitis de contacto alérgica en el 31,02% e irritativa en el 15,88%. El origen más común de la dermatitis fue profesional en el 16,66% de los casos, y la metalurgia y la construcción fueron las ocupaciones más prevalentes. Más de la mitad de los pacientes sufrían eccema en manos (54,34%). El alergeno más prevalente fue el níquel (26,64%) seguido de cobalto (9,89%) y cromo (8,66%). Conclusiones: Comparando los datos de este estudio con el realizado por el GEIDC en 1977 comprobamos cómo ha aumentado la alergia a níquel mientras ha disminuido la debida a cromo y cobalto. Alergenos no incluidos años atrás como tiomersal, mezcla de perfumes y Kathon CG muestran actualmente una alta prevalencia. Es siempre fundamental establecer la relevancia de las pruebas positivas, que es alta en este estudio para las gomas y para el níquel (AU)