Our skin is the largest organ of the body, serving as an important barrier against the harsh extrinsic environment. Alongside preventing desiccation, chemical damage and hypothermia, this barrier protects the body from invading pathogens through a sophisticated innate immune response and co-adapted consortium of commensal microorganisms, collectively termed the microbiota. These microorganisms inhabit distinct biogeographical regions dictated by skin physiology. Thus, it follows that perturbations to normal skin homeostasis, as occurs with ageing, diabetes and skin disease, can cause microbial dysbiosis and increase infection risk. In this review, we discuss emerging concepts in skin microbiome research, highlighting pertinent links between skin ageing, the microbiome and cutaneous repair. Moreover, we address gaps in current knowledge and highlight key areas requiring further exploration. Future advances in this field could revolutionise the way we treat microbial dysbiosis associated with skin ageing and other pathologies.

/pdf/the-skin-microbiome-current-landscape-and-future-1t8q0rr0.pdf

The Skin Microbiome: Current Landscape and Future Opportunities

SARS-CoV-2 has become one of the most studied viruses of the last century. It was assumed that the only possible host for these types of viruses was mammalian eukaryotic cells. Our recent studies show that microorganisms in the human gastrointestinal tract affect the severity of COVID-19 and for the first time provide indications that the virus might replicate in gut bacteria. In order to further support these findings, in the present work, cultures of bacteria from the human microbiome and SARS-CoV-2 were analyzed by electron and fluorescence microscopy. The images presented in this article, in association with the nitrogen (15N) isotope-labeled culture medium experiment, suggest that SARS-CoV-2 could also infect bacteria in the gut microbiota, indicating that SARS-CoV-2 could act as a bacteriophage. Our results add new knowledge to the understanding of the mechanisms of SARS-CoV-2 infection and fill gaps in the study of the interactions between SARS-CoV-2 and non-mammalian cells. These findings could be useful in suggesting specific new pharmacological solutions to support the vaccination campaign.

/pdf/could-sars-cov-2-have-bacteriophage-behavior-or-induce-the-j206vk4g.pdf

Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?

SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in gut microbiome bacteria. Many studies emphasize the importance of surface immunity and also that the mucosal system is critical in the interaction of the pathogen with the cells of the oral, nasal, pharyngeal, and intestinal epithelium. Recent studies have shown how bacteria in the human gut microbiome produce toxins capable of altering the classical mechanisms of interaction of viruses with surface cells. This paper presents a simple approach to highlight the initial behavior of a novel pathogen, SARS-CoV-2, on the human microbiome. The immunofluorescence microscopy technique can be combined with spectral counting performed at mass spectrometry of viral peptides in bacterial cultures, along with identification of the presence of D-amino acids within viral peptides in bacterial cultures and in patients’ blood. This approach makes it possible to establish the possible expression or increase of viral RNA viruses in general and SARS-CoV-2, as discussed in this study, and to determine whether or not the microbiome is involved in the pathogenetic mechanisms of the viruses. This novel combined approach can provide information more rapidly, avoiding the biases of virological diagnosis and identifying whether a virus can interact with, bind to, and infect bacteria and epithelial cells. Understanding whether some viruses have bacteriophagic behavior allows vaccine therapies to be focused either toward certain toxins produced by bacteria in the microbiome or toward finding inert or symbiotic viral mutations with the human microbiome. This new knowledge opens a scenario on a possible future vaccine: the probiotics vaccine, engineered with the right resistance to viruses that attach to both the epithelium human surface and gut microbiome bacteria.

/pdf/analysis-of-bacteriophage-behavior-of-a-human-rna-virus-sars-1ez7f5bk.pdf

Analysis of Bacteriophage Behavior of a Human RNA Virus, SARS-CoV-2, through the Integrated Approach of Immunofluorescence Microscopy, Proteomics and D-Amino Acid Quantification

Biophilic design based on indoor planting plays an important role in human physical and mental well-being. To investigate and assess the effects of indoor planting on air quality, we sequenced 16S rRNA gene amplicons to compare the airborne bacterial microbiomes of three planting rooms before and after installing natural materials (plants, soil, water, etc.) with distinct biophilic attributes. Incorporation of indoor plantings significantly increased the taxonomic diversity of the airborne microbiome in each room, and we observed different microbiome compositions in each room. The proportional contribution of each bacterial source to the airborne microbiome in the indoor planting rooms was estimated by SourceTracker2. This analysis revealed that the proportion of airborne microbial sources (e.g., plants and soil) varied depending on the natural materials installed. Our results have important implications for indoor planting with biophilic design to control the indoor airborne microbiome. 

/pdf/diversity-and-compositional-differences-of-the-airborne-166cxh19.pdf

Diversity and compositional differences of the airborne microbiome in a biophilic indoor environment

Following descriptive studies on skin microbiota in health and disease, mechanistic studies on the interplay between skin and microbes are on the rise, for which experimental models are in great demand. Here, we present a novel methodology for microbial colonization of organotypic skin and analysis thereof.An inoculation device ensured a standardized application area on the stratum corneum and a homogenous distribution of bacteria, while preventing infection of the basolateral culture medium even during prolonged culture periods for up to 2 weeks at a specific culture temperature and humidity. Hereby, host-microbe interactions and antibiotic interventions could be studied, revealing diverse host responses to various skin-related bacteria and pathogens.Our methodology is easily transferable to a wide variety of organotypic skin or mucosal models and different microbes at every cell culture facility at low costs. We envision that this study will kick-start skin microbiome studies using human organotypic skin cultures, providing a powerful alternative to experimental animal models in pre-clinical research. Video Abstract. 

Novel methodologies for host-microbe interactions and microbiome-targeted therapeutics in 3D organotypic skin models

The skin microbiota has been recognized to play an integral role in the physiology and pathology of the skin. The crosstalk between skin and the resident microbes has been extensively investigated using two-dimensional (2D) and three-dimensional (3D) cell cultures in vitro; however, skin colonization by multiple species and the effects of interspecific interactions on the structure and function of skin remains to be elucidated. This study reports the establishment of a mixed infection model, incorporating both commensal (Staphylococcus epidermidis) and pathogenic (Staphylococcus aureus) bacteria, based on a 3D human epidermal model. We observed that co-infecting the 3D epidermal model with S. aureus and S. epidermidis restricted the growth of S. aureus. In addition, S. aureus induced epidermal cytotoxicity, and the release of proinflammatory cytokines was attenuated by the S. aureus-S. epidermidis mixed infection model. S. epidermidis also inhibited the invasion of the deeper epidermis by S. aureus, eliciting protective effects on the integrity of the epidermal barrier. This 3D culture-based mixed infection model would be an effective replacement for existing animal models and 2D cell culture approaches for the evaluation of diverse biotic and abiotic factors involved in maintaining skin health.

/pdf/an-in-vitro-mixed-infection-model-with-commensal-and-heprj9srzd.pdf

An In Vitro Mixed Infection Model With Commensal and Pathogenic Staphylococci for the Exploration of Interspecific Interactions and Their Impacts on Skin Physiology

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An In Vitro Mixed Infection Model With Commensal and Pathogenic Staphylococci for the Exploration of Interspecific Interactions and Their Impacts on Skin Physiology