How to obtain an integrated picture of the molecular networks involved in adaptation to microgravity in different biological systems?

Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, "Biology in Space and Analogue Environments", focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present one of the identified topic areas, which is also an unanswered question of life science research in Space: "How to Obtain an Integrated Picture of the Molecular Networks Involved in Adaptation to Microgravity in Different Biological Systems?" The manuscript reports the main gaps of knowledge which have been identified by the community in the above topic area as well as the approach the community indicates to address the gaps not yet bridged. Moreover, the relevance that these research activities might have for the space exploration programs and also for application in industrial and technological fields on Earth is briefly discussed.

Ernica Clinical Consensus Statements on Total Colonic and Intestinal Aganglionosis.

BACKGROUND: Hirschsprung disease is a congenital intestinal motility disorder characterized by an absence of enteric ganglion cells. Total colonic aganglionosis and near total or total intestinal aganglionosis, defined as absence of ganglion cells in the entire colon and with variable length of small bowel involved, are life-threatening conditions which affect less than 10 % of all patients with Hirschsprung disease. The aim of this project was to develop clinical consensus statements within ERNICA, the European Reference Network for rare congenital digestive diseases, on four major topics: Surgical treatment of total colonic aganglionosis, surgical treatment of total intestinal aganglionosis, management of poor bowel function in total colonic and/or intestinal aganglionosis and long-term management in total colonic and or intestinal aganglionosis. METHODS: A multidisciplinary panel of representatives from ERNICA centers was invited to participate. Literature was searched, using specified search terms, in Medline (ALL), Embase and Google Scholar. Abstracts were screened and full text publications were selected. The panel was divided in four groups that extracted data from the full text publications and suggested draft statements for each of the major topics. A modified Delphi process was used to refine and agree on the statements. RESULTS: The consensus statement was conducted by a multidisciplinary panel of 24 participants from 10 European countries, 45 statements reached consensus after 3 Delphi-rounds. The availability of high-quality clinical evidence was limited, and most statements were based on expert opinion. Another 25 statements did not reach consensus. CONCLUSIONS: Total colonic and total intestinal aganglionosis are rare variants of Hirschsprung disease, with very limited availability of high-quality clinical evidence. This consensus statement provides statements on the surgical treatment, management of poor bowel function and long-term management for these rare patients. The expert panel agreed that patients benefit from multidisciplinary and personalized care, preferably in an expert center. TYPE OF STUDY: Clinical consensus statement. LEVEL OF EVIDENCE: 3a.

Yeast metagenomics: analytical challenges in the analysis of the eukaryotic microbiome.

Even if their impact is often underestimated, yeasts and yeast-like fungi represent the most prevalent eukaryotic members of microbial communities on Earth. They play numerous roles in natural ecosystems and in association with their hosts. They are involved in the food industry and pharmaceutical production, but they can also cause diseases in other organisms, making the understanding of their biology mandatory. The ongoing loss of biodiversity due to overexploitation of environmental resources is a growing concern in many countries. Therefore, it becomes crucial to understand the ecology and evolutionary history of these organisms to systematically classify them. To achieve this, it is essential that our knowledge of the mycobiota reaches a level similar to that of the bacterial communities. To overcome the existing challenges in the study of fungal communities, the first step should be the establishment of standardized techniques for the correct identification of species, even from complex matrices, both in wet lab practices and in bioinformatic tools.

Enhancing seafood traceability: tracking the origin of seabass and seabream from the tuscan coast area by the analysis of the gill bacterial communities.

BACKGROUND: The seafood consumption and trade have increased over the years, and along its expected expansion pose major challenges to the seafood industry and government institutions. In particular, the global trade in fish products and the consequent consumption are linked to reliable authentication, necessary to guarantee lawful trade and healthy consumption. Alterations or errors in this process can lead to commercial fraud and/or health threats. Consequently, the development of new investigative tools became crucial in ensuring unwanted scenarios. Here we used NGS techniques through targeted metagenomics approach on the V3-V4 region of the 16S rRNA genes to characterize the gill bacterial communities in wild-caught seabream (Sparus aurata) and seabass (Dicentrarchus labrax) within different fisheries areas of the "Costa degli Etruschi'' area in the Tuscan coast. Our challenge involved the possibility of discriminating between the microbiota of both fish species collected from three different fishing sites very close to each other (all within 100 km) in important areas from a commercial and tourist point of view. RESULTS: Our results showed a significant difference in the assembly of gill bacterial communities in terms of diversity (alpha and beta diversity) of both seabass and seabream in accordance with the three fishing areas. These differences were represented by a unique site -related bacterial signature, more evident in seabream compared to the seabass. Accordingly, the core membership of seabream specimens within the three different sites was minimal compared to the seabass which showed a greater number of sequence variants shared among the different fishing sites. Therefore, the LRT analysis highlighted the possibility of obtaining specific fish bacterial signatures associated with each site; it is noteworthy that specific taxa showed a unique association with the fishing site regardless of the fish species. This study demonstrates the effectiveness of target-metagenomic sequencing of gills in discriminating bacterial signatures of specimens collected from fishing areas located at a limited distance to each other. CONCLUSIONS: This study provides new information relating the structure of the gill microbiota of seabass and seabream in a fishing area with a crucial commercial and tourist interest, namely "Costa degli Etruschi". This study demonstrated that microbiome-based approaches can represent an important tool for validating the seafood origins with a central applicative perspective in the seafood traceability system.

Evaluation of the Impact of Near-Infrared Multiwavelength Locked System Laser Therapy on Skin Microbiome in Atopic Dogs.

Photobiomodulation (PBM) is a newly adopted consensus term to replace the therapeutic application of low-level laser therapy. It has been suggested that PMB influences the microbiome which, in turn, has increasingly been shown to be linked with health and disease. Even though the use of PBM has also grown dramatically in veterinary medicine, there is still a lack of evidence supporting its effect in vivo. Our objective was to investigate the impact of a dual-wavelength near-infrared laser source (Multiwavelength Locked Laser System, MLS®) on the skin microbiome in atopic dogs. Twenty adult-client-owned atopic dogs were enrolled in the study. The dogs were treated with MLS® laser therapy on one half of the abdominal region, whereas the contralateral side was left untreated and served as a control. Skin microbiome samples were collected before and after MLS® treatments, and then subjected to NGS-based ITS and 16S rRNA analysis. The results showed that while microbiome composition and diversity were not significantly affected, PBM could play a role in modulating the abundance of specific bacterial species, in particular Staphylococcus, that represent a major skin pathogenic strain. To the best of the authors' knowledge, this is the first study to investigate the potential impact of MLS® laser therapy on the skin microbiome in atopic dogs.

How are cell and tissue structure and function influenced by gravity and what are the gravity perception mechanisms?

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without gravity, helping us not only to understand the effects of gravitational alterations on biological systems but also the mechanisms underlying mechanoperception and cell/tissue response to mechanical and gravitational stresses. Despite the progress made so far, for future space exploration programs it is necessary to increase our knowledge on the mechanotransduction processes as well as on the molecular mechanisms underlying microgravity-induced cell and tissue alterations. This white paper reports the suggestions and recommendations of the SciSpacE Science Community for the elaboration of the section of the European Space Agency roadmap "Biology in Space and Analogue Environments" focusing on "How are cells and tissues influenced by gravity and what are the gravity perception mechanisms?" The knowledge gaps that prevent the Science Community from fully answering this question and the activities proposed to fill them are discussed.

Yeast strains isolated from fermented beverage produce extracellular vesicles with anti-inflammatory effects.

Extracellular vesicles (EVs) are lipid-bilayered particles, containing various biomolecules, including nucleic acids, lipids, and proteins, released by cells from all the domains of life and performing multiple communication functions. Evidence suggests that the interaction between host immune cells and fungal EVs induces modulation of the immune system. Most of the studies on fungal EVs have been conducted in the context of fungal infections; therefore, there is a knowledge gap in what concerns the production of EVs by yeasts in other contexts rather than infection and that may affect human health. In this work, we characterized EVs obtained by Saccharomyces cerevisiae and Pichia fermentans strains isolated from a fermented milk product with probiotic properties. The immunomodulation abilities of EVs produced by these strains have been studied in vitro through immune assays after internalization from human monocyte-derived dendritic cells. Results showed a significant reduction in antigen presentation activity of dendritic cells treated with the fermented milk EVs. The small RNA fraction of EVs contained mainly yeast mRNA sequences, with a few molecular functions enriched in strains of two different species isolated from the fermented milk. Our results suggest that one of the mechanisms behind the anti-inflammatory properties of probiotic foods could be mediated by the interactions of human immune cells with yeast EVs.

Ascomycetes yeasts: The hidden part of human microbiome.

The fungal component of the microbiota, the mycobiota, has been neglected for a long time due to its poor richness compared to bacteria. Limitations in fungal detection and taxonomic identification arise from using metagenomic approaches, often borrowed from bacteriome analyses. However, the relatively recent discoveries of the ability of fungi to modulate the host immune response and their involvement in human diseases have made mycobiota a fundamental component of the microbial communities inhabiting the human host, deserving some consideration in host-microbe interaction studies and in metagenomics. Here, we reviewed recent data on the identification of yeasts of the Ascomycota phylum across human body districts, focusing on the most representative genera, that is, Saccharomyces and Candida. Then, we explored the key factors involved in shaping the human mycobiota across the lifespan, ranging from host genetics to environment, diet, and lifestyle habits. Finally, we discussed the strengths and weaknesses of culture-dependent and independent methods for mycobiota characterization. Overall, there is still room for some improvements, especially regarding fungal-specific methodological approaches and bioinformatics challenges, which are still critical steps in mycobiota analysis, and to advance our knowledge on the role of the gut mycobiota in human health and disease. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Environmental Factors Infectious Diseases > Environmental Factors.

The yeast-human coevolution: Fungal transition from passengers, colonizers, and invaders.

Fungi are the cause of more than a billion infections in humans every year, although their interactions with the host are still neglected compared to bacteria. Major systemic fungal infections are very unusual in the healthy population, due to the long history of coevolution with the human host. Humans are routinely exposed to environmental fungi and can host a commensal mycobiota, which is increasingly considered as a key player in health and disease. Here, we review the current knowledge on host-fungi coevolution and the factors that regulate their interaction. On one hand, fungi have learned to survive and inhabit the host organisms as a natural ecosystem, on the other hand, the host immune system finely tunes the response toward fungi. In turn, recognition of fungi as commensals or pathogens regulates the host immune balance in health and disease. In the human gut ecosystem, yeasts provide a fingerprint of the transient microbiota. Their status as passengers or colonizers is related to the integrity of the gut barrier and the risk of multiple disorders. Thus, the study of this less known component of the microbiota could unravel the rules of the transition from passengers to colonizers and invaders, as well as their dependence on the innate component of the host's immune response. This article is categorized under: Infectious Diseases > Environmental Factors Immune System Diseases > Environmental Factors Infectious Diseases > Molecular and Cellular Physiology.

Species-specific gill's microbiome of eight crab species with different breathing adaptations.

Transitions to physically different environments, such as the water-to-land transition, proved to be the main drivers of relevant evolutionary events. Brachyuran crabs evolved remarkable morphological, behavioral, and physiological adaptations to terrestrial life. Terrestrial species evolved new respiratory structures devoted to replace or support the gills, a multifunctional organ devoted to gas exchanges, ion-regulation and nitrogen excretion. It was hypothesized that microorganisms associated with respiratory apparatus could have facilitated the processes of osmoregulation, respiration, and elimination of metabolites along this evolutionary transition. To test if crab species with different breathing adaptations may host similar microbial communities on their gills, we performed a comparative targeted-metagenomic analysis, selecting two marine and six terrestrial crabs belonging to different families and characterised by different breathing adaptations. We analysed anterior and posterior gills separately according to their different and specific roles. Regardless of their terrestrial or marine adaptations, microbial assemblages were strongly species-specific indicating a non-random association between the host and its microbiome. Significant differences were found in only two terrestrial species when considering posterior vs. anterior gills, without any association with species-specific respiratory adaptations. Our results suggest that all the selected species are strongly adapted to the ecological niche and specific micro-habitat they colonise.

Using wasps as a tool to restore a functioning vine grape mycobiota and preserve the mycobial "terroir".

In the last one-hundred years, the exponential expansion of wine making has artificialized the agricultural landscape as well as its microbial diversity, spreading human selected Saccharomyces cerevisiae strains. Evidence showed that social wasps can harbor a significant fraction of the yeast phenotypic diversity of a given area of wine production, allowing different strains to overwinter and mate in their gut. The integrity of the wasp-yeast ecological interaction is of paramount importance to maintain the resilience of microbial populations associated to wine aromatic profiles. In a field experiment, we verified whether Polistes dominula wasps, reared in laboratory and fed with a traceable S. cerevisiae strain, could be a useful tool to drive the controlled yeast dispersion directly on grapes. The demonstration of the biotechnological potential of social insects in organic wine farming lays the foundations for multiple applications including maintenance of microbial biodiversity and rewilding vineyards through the introduction of wasp associated microbiomes.

How do gravity alterations affect animal and human systems at a cellular/tissue level?

The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: "How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?" This is one of the five major scientific issues of the ESA roadmap "Biology in Space and Analogue Environments". Despite the many studies conducted so far on spaceflight adaptation mechanisms and related pathophysiological alterations observed in astronauts, we are not yet able to elaborate a synthetic integrated model of the many changes occurring at different system and functional levels. Consequently, it is difficult to develop credible models for predicting long-term consequences of human adaptation to the space environment, as well as to implement medical support plans for long-term missions and a strategy for preventing the possible health risks due to prolonged exposure to spaceflight beyond the low Earth orbit (LEO). The research activities suggested by the scientific community have the aim to overcome these problems by striving to connect biological and physiological aspects in a more holistic view of space adaptation effects.

Immunomodulatory Potential of Fungal Extracellular Vesicles: Insights for Therapeutic Applications.

Extracellular vesicles (EVs) are membranous vesicular organelles that perform a variety of biological functions including cell communication across different biological kingdoms. EVs of mammals and, to a lesser extent, bacteria have been deeply studied over the years, whereas investigations of fungal EVs are still in their infancy. Fungi, encompassing both yeast and filamentous forms, are increasingly recognized for their production of extracellular vesicles (EVs) containing a wealth of proteins, lipids, and nucleic acids. These EVs play pivotal roles in orchestrating fungal communities, bolstering pathogenicity, and mediating interactions with the environment. Fungal EVs have emerged as promising candidates for innovative applications, not only in the management of mycoses but also as carriers for therapeutic molecules. Yet, numerous questions persist regarding fungal EVs, including their mechanisms of generation, release, cargo regulation, and discharge. This comprehensive review delves into the present state of knowledge regarding fungal EVs and provides fresh insights into the most recent hypotheses on the mechanisms driving their immunomodulatory properties. Furthermore, we explore the considerable potential of fungal EVs in the realms of medicine and biotechnology. In the foreseeable future, engineered fungal cells may serve as vehicles for tailoring cargo- and antigen-specific EVs, positioning them as invaluable biotechnological tools for diverse medical applications, such as vaccines and drug delivery.

Differences in the inflammatory proteome of East African and Western European adults and associations with environmental and dietary factors.

Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in sub-Saharan Africa. Assessment of inflammatory and metabolic characteristics of a urbanizing African population and the comparison with populations outside Africa could provide insight in the pathophysiology of the rapidly increasing epidemic of NCDs, including the role of environmental and dietary changes. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we examined differences in the inflammatory proteome in healthy Tanzanian and healthy Dutch adults. We show that healthy Tanzanians display a pro-inflammatory phenotype compared to Dutch subjects, with enhanced activity of the Wnt/ß-catenin signalling pathway and higher concentrations of different metabolic regulators such as 4E-BP1 and fibroblast growth factor 21. Among the Tanzanian volunteers, food-derived metabolites were identified as an important driver of variation in inflammation-related molecules, emphasizing the potential importance of lifestyle changes. These findings endorse the importance of the current dietary transition and the inclusion of underrepresented populations in systems immunology studies.

Gut microbiota metabolites mediate the interplay between childhood maltreatment and psychopathology in patients with eating disorders.

Eating disorders (EDs) are syndromes with a multifactorial etiopathogenesis, involving childhood traumatic experiences, as well as biological factors. Human microbiome has been hypothesised to play a fundamental role, impacting on emotion regulation, as well as with eating behaviours through its metabolites such as short chain fatty acids (SCFAs). The present study investigated the interactions between psychopathology of EDs, the gut microbiome and SCFAs resulting from bacterial community metabolic activities in a population of 47 patients with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder and in healthy controls (HCs). Bacterial gut microbiota composition differences were found between subjects with EDs and HCs, especially in association with different pathological behaviours (binge-purge vs restricting). A mediation model of early trauma and ED-specific psychopathology linked reduction of microbial diversity to a typical microbiota-derived metabolite such as butyric acid. A possible interpretation for this model might be that childhood trauma represents a risk factor for gut dysbiosis and for a stable modification of mechanisms responsible for SCFAs production, and that this dysfunctional community is inherited in the passage from childhood to adulthood. These findings might open the way to novel interventions of butyric acid-like compounds as well as faecal transplant.

Vaginal Microbiome in Pregnant Women with and without Short Cervix.

Cervical shortening is a recognised risk factor for pre-term birth. The vaginal microbiome plays an essential role in pregnancy and in maternal and foetal outcomes. We studied the vaginal microbiome in 68 women with singleton gestation and a cervical length ≤25 mm and in 29 pregnant women with a cervix >25 mm in the second or early third trimester. Illumina protocol 16S Metagenomic Sequencing Library Preparation was used to detail amplified 16SrRNA gene. Statistical analyses were performed in R environment. Firmicutes was the phylum most represented in all pregnant women. The mean relative abundance of Proteobacteria and Actinobacteriota was higher in women with a short cervix. Bacterial abundance was higher in women with a normal length cervix compared to the group of women with a short cervix. Nonetheless, a significant enrichment in bacterial taxa poorly represented in vaginal microbiome was observed in the group of women with a short cervix. Staphylococcus and Pseudomonas, taxa usually found in aerobic vaginitis, were more common in women with a short cervix compared with the control group, while Lactobacillus iners and Bifidobacterium were associated with a normal cervical length. Lactobacillus jensenii and Gardenerella vaginalis were associated with a short cervix.

Conserved organ-specific microbial assemblages in different populations of a terrestrial crab.

Microorganisms are ubiquitous in the environment and provide genetic and physiological functions to multicellular organisms. Knowledge on the associated microbiota is becoming highly relevant to understand the host's ecology and biology. Among invertebrates, many examples of endosymbiosis have been described, such as those in corals, ants, and termites. At present, however, little is known on the presence, diversity, and putative roles of the microbiota associated to brachyuran crabs in relation to their environment. In this work we investigated the associated microbiota of three populations of the terrestrial brachyuran crab Chiromantes haematocheir to find evidence of a conserved organ-specific microbiome unrelated to the population of origin and dissimilar from environmental microbial assemblages. Bacterial 16S rRNA gene and fungal ITS sequences were obtained from selected crab organs and environmental matrices to profile microbial communities. Despite the presence of truly marine larval stages and the absence of a gregarious behaviour, favouring microbiota exchanges, we found common, organ-specific microbiota, associated with the gut and the gills of crabs from the different populations (with more than 15% of the genera detected specifically enriched only in one organ). These findings suggest the presence of possible functional roles of the organ-specific microbiota.

Mutualistic Relationships between Microorganisms and Eusocial Wasps (Hymenoptera, Vespidae).

Eusocial wasps are represented in the Vespidae by the subfamilies Stenogastrinae, Vespinae and Polistinae. These wasps present colonies that are sometimes composed of thousands of individuals which live in nests built with paper materials. The high density of the adult and larval population, as well as the stable micro environment of the nests, make very favourable conditions for the flourishing of various types of microorganisms. These microorganisms, which may be pathogens, are beneficial and certainly contribute to model the sociality of these insects. The mutualistic relationships that we observe in some species, especially in Actinomycete bacteria and yeasts, could have important fallouts for the development of new medicines and for the use of these insects in agricultural environments.

New Developments in Nutraceuticals and Functional Food Products: Microorganisms as Alternative Sources of Nutritive and Beneficial Components.

Microorganisms have long been essential to human life, playing significant roles in food and beverage production, health and disease, and the environment [...].

Adaptation of Commensal Escherichia coli in Tomato Fruits: Motility, Stress, Virulence.

Food contamination can be a serious concern for public health because it can be related to the severe spreading of pathogens. This is a main issue, especially in the case of fresh fruits and vegetables; indeed, they have often been associated with gastrointestinal outbreak events, due to contamination with pathogenic bacteria. However, little is known about the physiological adaptation and bacterial response to stresses encountered in the host plant. Thus, this work aimed to investigate the adaptation of a commensal E. coli strain while growing in tomato pericarp. Pre-adapted and non-adapted cells were compared and used to contaminate tomatoes, demonstrating that pre-adaptation boosted cell proliferation. DNA extracted from pre-adapted and non-adapted cells was sequenced, and their methylation profiles were compared. Hence, genes involved in cell adhesion and resistance against toxic compounds were identified as genes involved in adaptation, and their expression was compared in these two experimental conditions. Finally, pre-adapted and non-adapted E. coli were tested for their ability to resist the presence of toxic compounds, demonstrating that adaptation exerted a protective effect. In conclusion, this work provides new information about the physiological adaptation of bacteria colonizing the tomato fruit pericarp.