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.

Histological healing as a predictor of sustained clinical remission in paediatric ulcerative colitis.

BACKGROUND: The study aimed to assess the longitudinal impact of endoscopic healing (EH) and histological healing (HH) in a cohort of paediatric patients affected by ulcerative colitis (UC). METHODS: This was a retrospective single-centre longitudinal study. 86 children with UC who underwent endoscopic re-assessment while in clinical and biochemical remission were included. Partial EH was defined as a Mayo Endoscopic Subscore (MES) of 1 and complete EH was defined as a MES of 0. HH was defined as the absence of active inflammation in all biopsies. The cumulative incidence of clinical relapse was evaluated during follow-up. RESULTS: At the second endoscopic re-evaluation, 59 (68.6%) patients achieved EH (MES ≤1). Of these patients, 39 (66%) achieved complete EH. 20 of the 39 patients who achieved complete EH attained complete HH. Patients who achieved partial and complete EH showed higher recurrence-free survival rates compared to those who did not (p < 0.01 and p < 0.01, respectively). Amongst patients with complete EH, those who achieved complete HH had lower recurrence rates when compared to patients who still showed microscopic inflammation (p = 0.049). CONCLUSION: Achievement of EH and HH is associated with fewer disease relapses, with patients achieving HH showing longer relapse-free survival rates.

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.

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.

Induction of Remission With Exclusive Enteral Nutrition in Children With Crohn's Disease: Determinants of Higher Adherence and Response.

BACKGROUND: Exclusive enteral nutrition (EEN) is the first choice to induce remission and promote mucosal healing in pediatric Crohn's disease (CD). However, full adherence to EEN treatment may be problematic for children with CD. METHODS: The goal of the current multicenter retrospective study was to define predictive factors of nonadherence to treatment and nonremission at the end of induction treatment. Those data together were analyzed with the ultimate goal of trying to define an individualized induction treatment for children with CD. RESULTS: Three hundred seventy-six children with CD from 14 IBD pediatric referral centers were enrolled in the study. The rate of EEN adherence was 89%. Colonic involvement and fecal calprotectin >600 µg/g at diagnosis were found to be associated with a reduced EEN adherence. Exclusive enteral nutrition administered for 8 weeks was effective for inducing clinical remission in 67% of the total cohort. Factors determining lower remission rates were age >15 years and Pediatric Crohn's Disease Activity Index >50. CONCLUSION: Although EEN is extremely effective in promoting disease remission, several patients' related factors may adversely impact EEN adherence and response. Personalized treatments should be proposed that weigh benefits and risks based on the patient's disease location, phenotype, and disease activity and aim to promote a rapid control of inflammation to reduce long-term bowel damage.

Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain.

The composition of the intestinal microbiota plays a critical role in shaping the immune system. Modern lifestyle, the inappropriate use of antibiotics, and exposure to pollution have significantly affected the composition of commensal microorganisms. The intestinal microbiota has been shown to sustain inappropriate autoimmune responses at distant sites in animal models of disease, and may also have a role in immune-mediated central nervous system (CNS) diseases such as multiple sclerosis (MS). We studied the composition of the gut mycobiota in fecal samples from 27 persons with MS (pwMS) and in 18 healthy donors (HD), including 5 pairs of homozygous twins discordant for MS. We found a tendency towards higher fungal abundance and richness in the MS group, and we observed that MS twins showed a higher rate of food-associated strains, such as Saccharomyces cerevisiae. We then found that in pwMS, a distinct population of cells with antibacterial and antifungal activity is expanded during the remitting phase and markedly decreases during clinically and/or radiologically active disease. These cells, named MAIT (mucosal-associated invariant T cells) lymphocytes, were significantly more activated in pwMS compared to HD in response to S. cerevisiae and Candida albicans strains isolated from fecal samples. This activation was also mediated by fungal-induced IL-23 secretion by innate immune cells. Finally, immunofluorescent stainings of MS post-mortem brain tissues from persons with the secondary progressive form of the disease showed that MAIT cells cross the blood-brain barrier (BBB) and produce pro-inflammatory cytokines in the brain. These results were in agreement with the hypothesis that dysbiosis of the gut microbiota might determine the inappropriate response of a subset of pathogenic mucosal T cells and favor the development of systemic inflammatory and autoimmune diseases.

Resistance to Arsenite and Arsenate in Saccharomyces cerevisiae Arises through the Subtelomeric Expansion of a Cluster of Yeast Genes.

Arsenic is one of the most prevalent toxic elements in the environment, and its toxicity affects every organism. Arsenic resistance has mainly been observed in microorganisms, and, in bacteria, it has been associated with the presence of the Ars operon. In Saccharomyces cerevisiae, three genes confer arsenic resistance: ARR1, ARR2, and ARR3. Unlike bacteria, in which the presence of the Ars genes confers per se resistance to arsenic, most of the S. cerevisiae isolates present the three ARR genes, regardless of whether the strain is resistant or sensitive to arsenic. To assess the genetic features that make natural S. cerevisiae strains resistant to arsenic, we used a combination of comparative genomic hybridization, whole-genome sequencing, and transcriptomics profiling with microarray analyses. We observed that both the presence and the genomic location of multiple copies of the whole cluster of ARR genes were central to the escape from subtelomeric silencing and the acquisition of resistance to arsenic. As a result of the repositioning, the ARR genes were expressed even in the absence of arsenic. In addition to their relevance in improving our understanding of the mechanism of arsenic resistance in yeast, these results provide evidence for a new cluster of functionally related genes that are independently duplicated and translocated.

Changing Dietary Habits: The Impact of Urbanization and Rising Socio-Economic Status in Families from Burkina Faso in Sub-Saharan Africa.

(1) Background: Sub-Saharan Africa is experiencing the fastest urbanization worldwide. People in rural areas still have a traditional and rural lifestyle, whereas the Westernization of diet and lifestyle is already evident in urban areas. This study describes dietary habits of families in Burkina Faso living at different levels of urbanization. (2) Methods: Data on lifestyle, socio-economic conditions, health status and anthropometry were collected from 30 families living in rural villages, a small town and the capital city. A food frequency questionnaire and a 24 h recall diary were used to estimate dietary habits and macronutrients intake. (3) Results: The urban cohort showed a more diversified diet, with a higher intake of animal protein and, especially in children, a higher consumption of simple sugars. Fiber intake was significantly higher in the rural and semi-urbanized cohorts. As expected, overweight and obesity gradually increased with the level of urbanization. In semi-urbanized and urban families, we observed coexistence of under- and over-nutrition, whereas in rural families, a portion of children were wasted and stunted, and adults were underweight. (4) Conclusions: These three cohorts represent a model of the effect on diet of rural-to-urban migration. Rural diet and traditional habits are replaced by a Western-oriented diet when families move to urbanized areas. This dietary transition and increased socio-economic status in newly developing urban areas have a major impact on disease epidemiology, resembling the past evolution in Western countries.

Intestinal microbiota profiles in a genetic model of colon tumorigenesis correlates with colon cancer biomarkers.

Faecal (FM) and colon mucosal associated microbiota (MAM) were studied in a model of colorectal cancer (CRC), the Apc-mutated Pirc rats, and in age-paired wt F344 rats. Principal Coordinates Analysis indicated that samples' distribution was driven by age, with samples of young rats (1 month old; without tumours) separated from older ones (11-month-old; bearing tumours). Diversity analysis showed significant differences between FM and MAM in older Pirc rats, and between MAM of both Pirc and wt rats and the tumour microbiota, enriched in Enterococcus, Escherichia/Shigella, Proteus and Bifidobacteriaceae. In young animals, Pirc FM was enriched in the genus Delftia, while wt FM was enriched in Lactobacillus and Streptococcus. Some CRC biomarkers and faecal short chain fatty acids (SCFAs) were also measured. Colon proliferation and DClK1 expression, a pro-survival mucosal marker, were higher in Pirc than in wt rats, while the mucin MUC2, was lower in Pirc rats. Branched SCFAs were higher in Pirc than in wt animals. By Spearman analysis CRC biomarkers correlated with FM (in both young and old rats) and with MAM (in young rats), suggesting a specific relationship between the gut microbiota profile and these functional mucosal parameters deserving further investigation.

Anti-Tumor Necrosis Factor-Alpha Withdrawal in Children With Inflammatory Bowel Disease in Endoscopic and Histologic Remission.

BACKGROUND: The aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdrawal in selected pediatric patients with inflammatory bowel disease who achieved clinical remission and mucosal and histological healing (MH and HH). METHODS: A retrospective analysis was performed on children and adolescents affected by Crohn disease (CD) and ulcerative colitis (UC) who were followed up at 2 tertiary referral centers from 2008 through 2018. The main outcome measure was clinical relapse rates after ATA withdrawal. RESULTS: One hundred seventy patients received scheduled ATA treatment; 78 patients with CD and 56 patients with UC underwent endoscopic reassessment. We found that MH was achieved by 32 patients with CD (41%) and 30 patients with UC (53.6%); 26 patients with CD (33.3%) and 22 patients with UC (39.3%) achieved HH. The ATA treatment was suspended in 45 patients, 24 affected by CD and 21 by UC, who all achieved concurrently complete MH (Simplified Endoscopic Score for CD, 0; Mayo score, 0, respectively) and HH. All the patients who suspended ATA shifted to an immunomodulatory agent or mesalazine. In contrast, 17 patients, 8 with CD and 9 with UC, continued ATA because of growth needs, the persistence of slight endoscopic lesions, and/or microscopic inflammation. Thirteen out of 24 patients with CD who suspended ATA experienced disease relapse after a median follow-up time of 29 months, whereas no recurrence was observed among the 9 patients with CD who continued treatment (P = 0.05). Among the patients with UC, there were no significant differences in relapse-free survival among those who discontinued ATA and those who did not suspend treatment (P = 0.718). CONCLUSIONS: Despite the application of rigid selection criteria, ATA cessation remains inadvisable in CD. In contrast, in UC, the concurrent achievement of MH and HH may represent promising selection criteria to identify patients in whom treatment withdrawal is feasible.

Gut microbiota profiles and characterization of cultivable fungal isolates in IBS patients.

Studies so far conducted on irritable bowel syndrome (IBS) have been focused mainly on the role of gut bacterial dysbiosis in modulating the intestinal permeability, inflammation, and motility, with consequences on the quality of life. Limited evidences showed a potential involvement of gut fungal communities. Here, the gut bacterial and fungal microbiota of a cohort of IBS patients have been characterized and compared with that of healthy subjects (HS). The IBS microbial community structure differed significantly compared to HS. In particular, we observed an enrichment of bacterial taxa involved in gut inflammation, such as Enterobacteriaceae, Streptococcus, Fusobacteria, Gemella, and Rothia, as well as depletion of health-promoting bacterial genera, such as Roseburia and Faecalibacterium. Gut microbial profiles in IBS patients differed also in accordance with constipation. Sequence analysis of the gut mycobiota showed enrichment of Saccharomycetes in IBS. Culturomics analysis of fungal isolates from feces showed enrichment of Candida spp. displaying from IBS a clonal expansion and a distinct genotypic profiles and different phenotypical features when compared to HS of Candida albicans isolates. Alongside the well-characterized gut bacterial dysbiosis in IBS, this study shed light on a yet poorly explored fungal component of the intestinal ecosystem, the gut mycobiota. Our results showed a differential fungal community in IBS compared to HS, suggesting potential for new insights on the involvement of the gut mycobiota in IBS. KEY POINTS: • Comparison of gut microbiota and mycobiota between IBS and healthy subjects • Investigation of cultivable fungi in IBS and healthy subjects • Candida albicans isolates result more virulent in IBS subjects compared to healthy subjects.

Active microbial ecosystem in Iron-Age tombs of the Etruscan civilization.

Earth's microbial biosphere extends down through the crust and much of the subsurface, including those microbial ecosystems located within cave systems. Here, we elucidate the microbial ecosystems within anthropogenic 'caves'; the Iron-Age, subterranean tombs of central Italy. The interior walls of the rock (calcium-rich macco) were painted ~2500 years ago and are covered with CaCO3 needles (known as moonmilk). The aims of the current study were to: identify biological/geochemical/biophysical determinants of and characterize bacterial communities involved in CaCO3 precipitation; challenge the maxim that biogenic activity necessarily degrades surfaces; locate the bacterial cells that are the source of the CaCO3 precipitate; and gain insight into the kinetics of moonmilk formation. We reveal that this environment hosts communities that consist primarily of bacteria that are mesophilic for temperature and xerotolerance (including Actinobacteria, Bacteroidetes and Proteobacteria); is populated by photosynthetic Cyanobacteria exhibiting heterotrophic nutrition (Calothrix and Chroococcidiopsis); and has CaCO3 precipitating on the rock surfaces (confirmation that this process is biogenic) that acts to preserve rather than damage the painted surface. We also identified that some community members are psychrotolerant (Polaromonas), acidotolerant or acidophilic (members of the Acidobacteria), or resistant to ionizing radiation (Brevundimonas and Truepera); elucidate the ways in which microbiology impacts mineralogy and vice versa; and reveal that biogenic formation of moonmilk can occur rapidly, that is, over a period of 10 to 56 years. We discuss the paradox that these ecosystems, that are for the most part in the dark and lack primary production, are apparently highly active, biodiverse and biomass-rich.

Applications of Wild Isolates of Saccharomyces Yeast for Industrial Fermentation: The Gut of Social Insects as Niche for Yeast Hybrids' Production.

In the industry of fermented food and beverages, yeast cultures are often selected and standardized in order to ensure a better control of fermentation and a more stable product over time. Several studies have shown that the organoleptic characteristics of fermented products reflect geographic variations of the microbial community composition. Despite investigations of the worldwide distribution and genetic diversity of Saccharomyces cerevisiae, it is still unclear how and to what extent human intervention has shaped the brewer's yeast population structure. The genotypic and phenotypic characterization of environmental yeast populations and their potential application in the fermentative processes can significantly enrich the industrial fermentation products. Social insects have proven to be closely associated to the yeasts ecology. The relationships between yeasts and insects represent a fundamental aspect for understanding the ecological and evolutionary forces shaping their adaptation to different niches. Studies on phylogenetic relationships of S. cerevisiae populations showed genetic differences among strains isolated from gut and non-gut environments (i.e., natural sources and fermentation). Recent evidences showed that insect's gut is a reservoir and an evolutionary niche for Saccharomyces, contributing to its survival and evolution, favoring its dispersion, mating and improving the inter-specific hybrids production during hibernation. Here, we discuss the potential use of social insects for production of a wide range of hybrid yeasts from environmental Saccharomyces isolates suitable for industrial and biotechnological applications.

Identification of Vaginal Microbial Communities Associated with Extreme Cervical Shortening in Pregnant Women.

The vaginal microbiota plays a critical role in pregnancy. Bacteria from Lactobacillus spp. are thought to maintain immune homeostasis and modulate the inflammatory responses against pathogens implicated in cervical shortening, one of the risk factors for spontaneous preterm birth. We studied vaginal microbiota in 46 pregnant women of predominantly Caucasian ethnicity diagnosed with short cervix (<25 mm), and identified microbial communities associated with extreme cervical shortening (≤10 mm). Vaginal microbiota was defined by 16S rRNA gene sequencing and clustered into community state types (CSTs), based on dominance or depletion of Lactobacillus spp. No correlation between CSTs distribution and maternal age or gestational age was revealed. CST-IV, dominated by aerobic and anaerobic bacteria different than Lactobacilli, was associated with extreme cervical shortening (odds ratio (OR) = 15.0, 95% confidence interval (CI) = 1.56-14.21; p = 0.019). CST-III (L. iners-dominated) was also associated with extreme cervical shortening (OR = 6.4, 95% CI = 1.32-31.03; p = 0.02). Gestational diabetes mellitus (GDM) was diagnosed in 10/46 women. Bacterial richness was significantly higher in women experiencing this metabolic disorder, but no association with cervical shortening was revealed by statistical analysis. Our study confirms that Lactobacillus-depleted microbiota is significantly associated with an extremely short cervix in women of predominantly Caucasian ethnicity, and also suggests an association between L. iners-dominated microbiota (CST III) and cervical shortening.

Saccharomyces cerevisiae - Insects Association: Impacts, Biogeography, and Extent.

Over the last few years, an increasing number of studies have reported the existence of an association between the budding yeast Saccharomyces cerevisiae and insects. The discovery of this relationship has called into question the hypothesis that S. cerevisiae is unable to survive in nature and that the presence of S. cerevisiae strains in natural specimens is the result of contamination from human-related environments. S. cerevisiae cells benefit from this association as they find in the insect intestine a shelter, but also a place where they can reproduce themselves through mating, the latter being an event otherwise rarely observed in natural environments. On the other hand, insects also take advantage in hosting S. cerevisiae as they rely on yeasts as nutriment to properly develop, to localize suitable food, and to enhance their immune system. Despite the relevance of this relationship on both yeast and insect ecology, we are still far from completely appreciating its extent and effects. It has been shown that other yeasts are able to colonize only one or a few insect species. Is it the same for S. cerevisiae cells or is this yeast able to associate with any insect? Similarly, is this association geographically or topographically limited in areas characterized by specific physical features? With this review, we recapitulate the nature of the S. cerevisiae-insect association, disclose its extent in terms of geographical distribution and species involved, and present YeastFinder, a cured online database providing a collection of information on this topic.

Comparative immunophenotyping of Saccharomyces cerevisiae and Candida spp. strains from Crohn's disease patients and their interactions with the gut microbiome.

Investigation of the fungal communities in animal models of Inflammatory Bowel Diseases (IBD) showed a controversial role of Saccharomyces cerevisiae and Candida spp. In health and disease. These conflicting observations could be ascribed to immunogenic differences among co-specific strains. To assess the relevance of intra-strains differences on yeast immunogenicity and impact on the microbiota, we screened S. cerevisiae and Candida spp. Strains isolated from fecal samples of IBD patients. We compared the cytokine profiles, obtained upon stimulation of Peripheral Blood Mononuclear Cells (PBMCs) and Dendritic Cells with different yeast strains, and evaluated the relationship between strain's cell wall sugar amount and immune response. Moreover, the gut microbiota composition was explored in relation to fungal isolation from fecal samples by metabarcoding analysis. The comparison of cytokine profiles showed strain dependent rather than species-dependent differences in immune responses. Differences in immunogenicity correlated with the cell wall composition of S. cerevisiae intestinal strains. Stimulation of human healthy PBMCs with different strains showed a pro-inflammatory IL-6 response counterbalanced by IL-10 production. Interestingly, Crohn's (CD) patients responded differently to "self" and "non-self" strains, eliciting pure Th1 or Th17 cytokine patterns. The differences observed in vitro were recapitulated in vivo, where different strains contributed in dramatically different ways to local epithelial activity and to the inflammation of wild type and Interleukin-deficient mice. Furthermore, we observed that the gut microbiota profiles significantly differentiated according to the presence of Saccharomyces or Candida spp. or the absence of fungal isolates in fecal samples. Our results show the importance to deepen metagenomics and immunophenotyping analyses to the strain level, to elucidate the role of fungal and bacterial communities in health and disease.

IL-13 mRNA Tissue Content Identifies Two Subsets of Adult Ulcerative Colitis Patients With Different Clinical and Mucosa-Associated Microbiota Profiles.

BACKGROUND AND AIMS: A personalized approach to therapy hold great promise to improve disease outcomes. To this end, the identification of different subsets of patients according to the prevalent pathogenic process might guide the choice of therapeutic strategy. We hypothesize that ulcerative colitis [UC] patients might be stratified according to distinctive cytokine profiles and/or to a specific mucosa-associated microbiota. METHODS: In a cohort of clinically and endoscopic active UC patients and controls, we used quantitative PCR to analyse the mucosal cytokine mRNA content and 16S rRNA gene sequencing to assess the mucosa-associated microbiota composition. RESULTS: We demonstrate, by means of data-driven approach, the existence of a specific UC patient subgroup characterized by elevated IL-13 mRNA tissue content separate from patients with low IL-13 mRNA tissue content. The two subsets differ in clinical-pathological characteristics. High IL-13 mRNA patients are younger at diagnosis and have a higher prevalence of extensive colitis than low IL-13 mRNA patients. They also show more frequent use of steroid/immunosuppressant/anti-tumour necrosis factor α therapy during 1 year of follow-up. The two subgroups show differential enrichment of mucosa-associated microbiota genera with a prevalence of Prevotella in patients with high IL-13 mRNA tissue content and Sutterella and Acidaminococcus in patients with low IL-13 mRNA tissue content. CONCLUSION: Assessment of mucosal IL-13 mRNA might help in the identification of a patient subgroup that might benefit from a therapeutic approach modulating IL-13. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Gut microbiota composition in Himalayan and Andean populations and its relationship with diet, lifestyle and adaptation to the high-altitude environment.

Human populations living at high altitude evolved a number of biological adjustments to cope with a challenging environment characterised especially by reduced oxygen availability and limited nutritional resources. This condition may also affect their gut microbiota composition. Here, we explored the impact of exposure to such selective pressures on human gut microbiota by considering different ethnic groups living at variable degrees of altitude: the high-altitude Sherpa and low-altitude Tamang populations from Nepal, the high-altitude Aymara population from Bolivia, as well as a low-altitude cohort of European ancestry, used as control. We thus observed microbial profiles common to the Sherpa and Aymara, but absent in the low-altitude cohorts, which may contribute to the achievement of adaptation to high-altitude lifestyle and nutritional conditions. The collected evidences suggest that microbial signatures associated to these rural populations may enhance metabolic functions able to supply essential compounds useful for the host to cope with high altitude-related physiological changes and energy demand. Therefore, these results add another valuable piece of the puzzle to the understanding of the beneficial effects of symbiosis between microbes and their human host even from an evolutionary perspective.

Saccharomyces cerevisiae Induces Immune Enhancing and Shapes Gut Microbiota in Social Wasps.

Trained immunity is the enhanced response of the innate immune system to a secondary infection after an initial encounter with a microorganism. This non-specific response to reinfection is a primitive form of adaptation that has been shown to be conserved from plants to mammals. Insects lack an acquired immune component and rely solely on an innate one, and they have expanded it upon traits of plasticity and adaptation against pathogens in the form of immune priming. The recent discoveries of the role of Saccharomyces cerevisiae in the insect's ecology and the ability of this yeast to induce trained immunity in different organisms suggest that insects could have developed mechanisms of adaptation and immune enhancing. Here, we report that two yeast strains of S. cerevisiae, previously shown to induce trained immunity in mammals, enhance resistance to Escherichia coli infection in the paper wasp Polistes dominula. The reduction of injected E. coli load by S. cerevisiae strains was statistically significant in future foundresses but not in workers, and this occurs before and after hibernation. We thus investigated if the effect on E. coli was mirrored by variation in the gut microbiota composition. Foundresses, showing immune enhancing, had statistically significant changes in composition and diversity of gut bacterial communities but not in the fungal communities. Our results demonstrate that S. cerevisiae can prime insect responses against bacterial infections, providing an advantage to future foundress wasps to carry these microorganisms. Understanding the mechanisms involved in the generation of specific and long-lasting immune response against pathogenic infections in insects and the influence of the induction of trained immunity on the commensal gut microbiota could have a major impact on modern immunology.