Academic literature on the topic 'Mycobiote intestinal'

The cynomolgus macaque, Macaca fascicularis, is a non-human primate (NHP) widely used in biomedical research as its genetics, immunology and physiology are similar to those of humans. They may also be a useful model of the intestinal microbiome as their prokaryome resembles that of humans. However, beyond the prokaryome relatively little is known about other constituents of the macaque intestinal microbiome including the mycobiome. Here, we conducted a region-by-region taxonomic survey of the cynomolgus intestinal mycobiota, from duodenum to distal colon, of sixteen captive animals of differing age (from young to old). Using a high-throughput ITS1 amplicon sequencing-based approach, the cynomolgus gut mycobiome was dominated by fungi from the Ascomycota phylum. The budding yeast genus Kazachstania was most abundant, with the thermotolerant species K. pintolopesii highly prevalent, and the predominant species in both the small and large intestines. This is in marked contrast to humans, in which the intestinal mycobiota is characterised by other fungal genera including Candida and Saccharomyces, and Candida albicans. This study provides a comprehensive insight into the fungal communities present within the captive cynomolgus gut, and for the first time identifies K. pintolopesii as a candidate primate gut commensal.

Intestinal microorganisms impact health by maintaining gut homeostasis and shaping the host immunity, while gut dysbiosis associates with many conditions, including autism, a complex neurodevelopmental disorder with multifactorial aetiology. In autism, gut dysbiosis correlates with symptom severity and is characterised by a reduced bacterial variability and a diminished beneficial commensal relationship. Microbiota can influence the expression of host microRNAs that, in turn, regulate the growth of intestinal bacteria by means of bidirectional host-gut microbiota cross-talk. We investigated possible interactions among intestinal microbes and between them and host transcriptional modulators in autism. To this purpose, we analysed, by “omics” technologies, faecal microbiome, mycobiome, and small non-coding-RNAs (particularly miRNAs and piRNAs) of children with autism and neurotypical development. Patients displayed gut dysbiosis related to a reduction of healthy gut micro- and mycobiota as well as up-regulated transcriptional modulators. The targets of dysregulated non-coding-RNAs are involved in intestinal permeability, inflammation, and autism. Furthermore, microbial families, underrepresented in patients, participate in the production of human essential metabolites negatively influencing the health condition. Here, we propose a novel approach to analyse faeces as a whole, and for the first time, we detected miRNAs and piRNAs in faecal samples of patients with autism.

Abstract Sensing of the gut microbiota, including fungi, regulates mucosal immunity. Whether fungal sensing in the gut can influence immunity at other body sites is unknown. Here we show that fluconazole-induced gut fungal dysbiosis has persistent effects on allergic airway disease in a house dust mite challenge model. Mice with a defined community of bacteria, but lacking intestinal fungi were not susceptible to fluconazole-induced dysbiosis, while colonization with a fungal mixture recapitulated the detrimental effects. Gut-resident mononuclear phagocytes (MNPs) expressing the fractalkine receptor CX3CR1 were essential for the effect of gut fungal dysbiosis on peripheral immunity. However, how mycobiota influence immunity in gut distal sites is not well understood. We developed protocols for gut-targeted depletion of phagocytes to investigate the influence of fungi on gut-lung crosstalk. Depletion of CX3CR1+ MNPs or selective inhibition of Syk signaling downstream of fungal sensing in these cells ameliorated lung allergy. These results indicate that disruption of intestinal fungal communities can mediate gut-lung-directed immune crosstalk and aggravate disease severity through fungal sensing by gut-resident CX3CR1+ MNPs. Highlights Gut fungal dysbiosis persistently aggravates allergic airway disease (AAD) in mice. Gut colonization by commensal fungi is both required and sufficient to aggravate AAD in a mycobiome-free mouse model. Intestinal CX3CR1+ mononuclear phagocytes (MNPs) are essential for the systemic effects of gut fungal dysbiosis on AAD. Inhibition of Syk-mediated fungal sensing in intestinal CX3CR1+ MNPs ameliorates AAD.

Host–microbiota interactions are critical in regulating mammalian health and disease. In addition to bacteria, parasites, and viruses, beneficial communities of fungi (the mycobiome) are important modulators of immune- and tissue-homeostasis. Chitin is a major component of the fungal cell wall, and fibrinogen C containing domain 1 (FIBCD1) is a chitin-binding protein; however, the role of this molecule in influencing host–mycobiome interactions in vivo has never been examined. Here, we identify direct binding of FIBCD1 to intestinal-derived fungi and demonstrate that epithelial-specific expression of FIBCD1 results in significantly reduced fungal colonization and amelioration of fungal-driven intestinal inflammation. Collectively, these results identify FIBCD1 as a previously unrecognized microbial pattern recognition receptor through which intestinal epithelial cells can recognize and control fungal colonization, limit fungal dysbiosis, and dampen intestinal inflammation.

This review explores the ‘gut–lung axis’ in asthma with a focus on commensal fungal organisms. We explore how changes to the intestinal commensal fungal community composition alter lung immune function. We comprehensively review available studies that have profiled the composition of the gut mycobiome in adults and children with asthma, and discuss mechanisms of gut–lung interactions that have been described in animal models of asthma. Studies indicate that intestinal fungal dysbiosis, such as an increased abundance of certain fungi like Candida, can elevate the risk of asthma in children and exacerbate it in adults. This effect is mediated through various pathways: the host immune system’s sensing of dysbiosis via C-type lectin receptors (e.g., Dectin-2), the impact of pro-inflammatory fungal metabolites (e.g., 12,13-diHOME, prostaglandin E2), and the role of lung immune cells (e.g., group 2 innate lymphoid cells [ILC2], M2 macrophages). We also describe strategies for modulating the gut mycobiome as potential therapies for severe asthma. The review concludes by emphasizing the necessity for further research into the role of the gut mycobiome in asthma to deepen our understanding of these complex interactions.

The gut microbiome comprised of microbes from multiple kingdoms, including bacteria, fungi, and viruses. Emerging evidence suggests that the intestinal fungi (the gut “mycobiome”) play an important role in host immunity and inflammation. Advances in next generation sequencing methods to study the fungi in fecal samples and mucosa tissues have expanded our understanding of gut fungi in intestinal homeostasis and systemic immunity in health and their contribution to different human diseases. In this review, the current status of gut mycobiome in health, early life, and different diseases including inflammatory bowel disease, colorectal cancer, and metabolic diseases were summarized.

Background: Dysbiosis of the intestinal flora has emerged as an oncogenic contributor in different malignancies. Recent findings suggest a crucial tumor-promoting role of micro- and mycobiome alterations also in the development of pancreatic ductal adenocarcinoma (PDAC). Methods: To summarize the current knowledge about this topic, a systematic literature search of articles published until October 2020 was performed in MEDLINE (PubMed). Results: An increasing number of publications describe associations between bacterial and fungal species and PDAC development. Despite the high inter-individual variability of the commensal flora, some studies identify specific microbial signatures in PDAC patients, including oral commensals like Porphyromonas gingivalis and Fusobacterium nucleatum or Gram-negative bacteria like Proteobacteria. The role of Helicobacter spp. remains unclear. Recent isolation of Malassezia globosa from PDAC tissue suggest also the mycobiota as a crucial player of tumorigenesis. Based on described molecular mechanisms and interactions between the pancreatic tissue and the immune system this review proposes a model of how the micro- and the mycobial dysbiosis could contribute to tumorigenesis in PDAC. Conclusions: The presence of micro- and mycobial dysbiosis in pancreatic tumor tissue opens a fascinating perspective on PDAC oncogenesis. Further studies will pave the way for novel tumor markers and treatment strategies.

Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut fungal communities (mycobiota) remain unknown. We identified CX3CR1+mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+MNPs in mice led to changes in gut fungal communities and to severe colitis that was rescued by antifungal treatment. In Crohn’s disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired antifungal responses. These results unravel a role of CX3CR1+MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.

Introduction. Alors que le mycobiote représente une part quantitative négligeable, en apparence, du microbiote intestinal, les preuves de son rôle dans les maladies inflammatoires chroniques de l’intestin, et notamment la maladie de Crohn (MC), sont croissantes. Ce travail avait pour objectif d’évaluer l’impact de Candida albicans et Saccharomyces cerevisiae sur l’inflammation et la fibrose intestinale (FI), mais également sur la production des anticorps anti-S. cerevisiae (ASCA), reconnaissant des séquences oligomannosidiques de faible degré de polymérisation ayant un résidu α,1-3 mannose terminal.Méthodes. Des modèles murins (C57BL/6, axénique et CEABAC10 exprimant CEACAM6 humaine) et cellulaires (fibroblaste CCD-18Co et cellule épithéliale intestinale Caco-2) d’inflammation et de FI induites (par sulfate de dextrane sodique ou TGF-β) ont été utilisés pour évaluer les réponses cellulaires, tissulaires et systémiques aux levures et à la souche bactérienne LF82, souche adhérente invasive d’Escherichia coli (AIEC) utilisée comme témoin, par analyse histologique, RT-q-PCR et détermination des ASCA. Parallèlement, une analyse métagénomique (MTG) du mycobiote fécal et la détermination des ASCA et de la calprotectine fécale étaient réalisés dans le cadre d’une étude cas-témoins, « MAGIC », incluant des sujets atteints de la MC de diagnostic récent et en rémission clinique comparés à leurs apparentés sains du premier degré, ainsi qu’à des témoins sains appariés. Cette étude était réalisée en collaboration avec d’autres équipes de recherche, analysant notamment le microbiote fécal bactérien et caractérisant les souches AIEC.Résultats. Dans le modèle murin de FI chimio-induite, LF82 aggravait l’inflammation et la FI cliniquement, microscopiquement et à l’échelle de l’expression génique (EG). C. albicans augmentait l’EG surtout des marqueurs de l’inflammation alors que S. cerevisiae n’avait pas d’effet. In vitro, seules les cellules épithéliales répondaient au TGF-β et/ou à LF82 et l’EG des marqueurs pro-fibrotiques était augmentée, tandis que les levures n’avaient pas d’effet sur la FI. Par ailleurs, les levures n’induisaient pas la synthèse d’ASCA chez les différents modèles murins étudiés. Dans l’étude clinique MAGIC, 41,7% des patients atteints de la MC étaient porteurs d’ASCA, 2,9% des apparentés sains et 1,8% des témoins sains, aucune différence n’était observée selon l’âge. L’analyse MTG bactérienne, montrait un profil spécifique chez les apparentés sains (richesse et AIEC plus élevées) vs. témoins et patients atteints de MC, liée notamment à la présence de bactéries symbiontes, mais également la présence plus élevée d’AIEC vs. témoins ; les patients atteints de MC présentaient une diversité plus basse vs. témoins et apparentés sains, ainsi que la présence d’AIEC plus élevée vs. témoins. Cependant, le mycobiote fécal était similaire entre les différents groupes, que ce soit en abondance relative (notamment pour C. albicans et S. cerevisiae), ou en alpha-, beta-diversités. Aucune association n’a été retrouvée entre micromycètes et les différents paramètres évalués (calprotectine, ASCA, AIEC).Conclusion. Dans les limites des modèles utilisés, les levures ici étudiées n’avaient pas d’impact sur la FI, contrairement à LF82, et ne semblaient pas être responsables de la synthèse d’ASCA. L’hypothèse de l’auto-anticorps reste à approfondir. L’analyse MTG fongique des selles des sujets de l’étude MAGIC fait suggérer que les modifications observées dans d’autres études seraient une conséquence de la MC. En effet, l’absence de profil fongique spécifique pourraient s’expliquer par le fait que les sujets inclus atteints de MC présentaient un diagnostic récent et donc un profil fongique peu modifié à ce stade de la maladie. Toutefois, la qualité de ces données justifie que ces résultats soient confirmés sur une large cohorte de patients atteints de MC suivis de manière séquentielle en début et au décours de la maladie
Introduction. While the mycobiota represents a seemingly negligible quantitative proportion of the intestinal microbiota, evidence of its role in chronic inflammatory bowel diseases, and in particular in Crohn's disease (CD), is growing. This work aimed to evaluate the impact of Candida albicans and Saccharomyces cerevisiae on inflammation and intestinal fibrosis (IF), but also on the production of anti-S. cerevisiae antibodies (ASCA), recognizing oligomannosidic sequences of low degree of polymerization having a terminal α, 1-3 mannose residue.Methods. Murine (C57BL/6, axenic and CEABAC10 expressing human CEACAM6) and cellular (CCD-18Co fibroblast and Caco-2 intestinal epithelial cell) models of induced inflammation and IF (by DSS or TGF-β) were used to evaluate cellular, tissue and systemic responses to yeasts and bacterial strain LF82, invasive adherent strain of E. coli (AIEC) used as control, by histological analysis, RT-q-PCR and determination of ASCA. Alongside, a metagenomic (MTG) analysis of the fecal mycobiota and the determination of ASCA and fecal calprotectin were carried out as part of a case-control study, “MAGIC”. This study included subjects with recently diagnosed CD and in clinical remission in comparison to their healthy first-degree relatives, as well as to matched healthy controls. This study was carried out in collaboration with other research teams, analyzing in particular the bacterial fecal microbiota and carrying out the characterization of AIEC strains.Results. In the mouse model of chemo-induced IF, LF82 worsened inflammation and IF, clinically, microscopically and at the level of gene expression (GE). C. albicans increased the GE especially of markers of inflammation. S. cerevisiae had no effect. In vitro, only epithelial cells responded to TGF-β and/or LF82 and the GE of pro-fibrotic markers was increased, while yeast had no effect on IF. Furthermore, yeasts did not induce the synthesis of ASCA in the different mouse models studied. In the MAGIC clinical study, 41.7% of CD patients carried ASCA, 2.9% of healthy relatives and 1.8% of healthy controls and no difference was observed according to age. Bacterial MTG analysis showed a specific profile in healthy relatives (higher richness and AIEC) vs. controls and MC patients, particularly linked to the presence of symbionts bacteria, but also the higher presence of AIEC vs. controls; patients with CD had lower diversity vs. healthy controls and relatives, as well as the presence of higher AIEC vs. controls. However, the fecal mycobiota was similar between the different groups, whether in relative abundance (notably for C. albicans and S. cerevisiae), or in alpha- beta-diversity. No association between micromycetes and the different parameters evaluated (calprotectin, ASCA, AIEC) was found.Conclusion. These results suggest, within the limits of the models used, that the studied yeasts do not have an impact on IF, unlike LF82, and do not seem responsible for the synthesis of ASCA. The autoantibody hypothesis remains to be further explored. Fecal fungal MTG analysis of the individuals included in the MAGIC study suggests that the changes observed in other studies are a consequence of CD. Indeed, the absence of a specific fungal profile could be explained by the fact that the included subjects suffering from CD had a recent diagnosis and therefore had a little modified fungal profile at this stage of the disease. However, the quality of these data warrants that these results be confirmed in a large cohort of patients with CD followed sequentially at the beginning and throughout the course of the disease

Introduction : La maladie de Crohn (MC), maladie inflammatoire chronique intestinale, est une maladie multifactorielle, d’origine inconnue. La dysbiose bactérienne a été largement évoquée dans la pathogénèse de la MC. Notre objectif était de caractériser la flore fongique, conjointement à la flore bactérienne au cours de formes familiales de MC.Méthodes: Nous avons utilisé une plateforme de séquençage à haut débit pour caractériser la flore fongique et bactérienne fécale, échantillonnée dans 9 familles multiplexes atteints de MC (20 patients, et 28 sujets sains apparentés), et 4 familles contrôles (21 individus sains non apparentés). Une analyse bioinformatique a été réalisée pour analyser l’abondance, la biodiversité, et les interactions microbiennes.Résultats : Le microbiote fécal des membres issus des familles multiplexes était statistiquement différent de celui des membres issus des familles contrôles. L’analyse en composantes principales a montré qu’au sein des familles multiplexes, les membres malades et sains partageaient un répertoire fongique commun. Les patients MC avaient en revanche un microbiote enrichi en Candida tropicalis, Escherichia coli et en Serratia marcescens, et appauvri en bactéries dites bénéfiques (Faecalibacterium prausnitzii). De plus les taux d’ASCA (Anticorps anti- S. cerevisiae), marqueur sérologique de MC étaient corrélées à la présence de C. tropicalis (P = .01). Enfin nous avons mis en évidence une synergie entre C. tropicalis, E. coli, et S. marcescens, suggérant une interaction microbienne in vivo participant à l’initiation de l’inflammation intestinale. Ces données ont été validées par la suite avec un modèle de biofilm.Conclusion : Dans ces formes familiales de MC, les interactions microbiennes entre bactéries et champignons sont déterminantes dans l’initiation de la réponse inflammatoire
Introduction: Crohn's disease (CD) results from a complex interplay between host genetic factors and endogenous microbial communities.Methods: In the current study, we used Ion Torrent sequencing to characterize the gut bacterial microbiota (bacteriome) and fungal community (mycobiome) in patients with CD and their non-diseased first degree relatives (NCDR) in 9 familial clusters living in Northern France/Belgium, and in healthy individuals from 4 families living in the same area (non-CD unrelated, NCDU). Principal components analysis, diversity, and abundance analyses were conducted and CD-associated inter- and intra-kingdom microbial correlations determined. Significant microbial interactions were identified and validated using single- and mixed-species biofilms.Results: CD and NCDR groups clustered together in the mycobiome, but not in bacteriome. Microbiota of familial (CD, NCDR) samples were distinct from that of non-familial (NCDU) samples. Abundance of Serratia marcescens (SM), Escherichia coli (EC) was elevated in CD patients, while that of beneficial bacteria was decreased. Abundance of the fungus Candida tropicalis (CT) was significantly higher in CD compared to NCDR (P = .003), and positively correlated with levels of anti–Saccharomyces cerevisiae antibody (ASCA). Abundance of CT was positively correlated with SM and EC, suggesting these organisms interact in the gut. The mass and thickness of Triple species (CT+SM+EC) biofilm were significantly higher than single and double species biofilm. CT biofilms comprised of blastospores, while double and triple species biofilms were enriched in hyphae. SM used fimbriae to co-aggregate or attach with CT/EC, while EC closely apposed with CT. Conclusion: Specific inter-kingdom microbial interactions may be key determinants in CD

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Os fungos têm um papel complexo no trato intestinal, influenciando diretamente na saúde e na doença e sua disbiose pode contribuir para a obesidade. O objetivo deste estudo foi avaliar a diversidade de fungos da microbiota intestinal humana entre indivíduos eutróficos, com sobrepeso e obesos. Foram coletados espécimes fecais de 72 indivíduos adultos e análises dependentes e independentes de cultivo foram realizadas para avaliar os fungos presentes. As leveduras foram identificadas pela técnica de ionização e dessorção a laser assistida por matriz acoplada a analisador do tipo espectro de massa por tempo de vôo (MALDI-TOF MS) e os fungos filamentosos por microcultivo. A contagem média de fungos filamentosos e leveduras cultiváveis foi de 1,58 Log10 UFC/g de fezes. Diferenças significativas no nível populacional dos fungos filamentosos foi observado entre os grupos dos indivíduos eutróficos e obesos. Trinta e quatro gêneros de fungos foram identificados. O filo predominante foi Ascomycota com 29 gêneros e/ou espécies diferentes, seguido por Zigomycota e Basidiomycota. O fungo mais isolado nos indivíduos eutróficos foi Paecylomyces sp. e nos indivíduos obesos Penicillium sp. Os indivíduos eutróficos apresentam uma diversidade ligeiramente maior de fungos filamentosos do que os indivíduos obesos. Os indivíduos do sexo feminino tiveram um maior número de fungos diferentes quando comparados aos do sexo masculino. A análise de eletroforese em gel de gradiente desnaturante (DGGE) mostrou agrupamento dos indivíduos eutróficos e com sobrepeso em um cluster e dos indivíduos obesos em outro cluster distinto, embora a riqueza tenha sido baixa nos três grupos. A análise de hibridização in situ florescente (FISH) demonstrou maior densidade relativa de C. albicans no grupo obeso quando comparado ao eutrófico e pela análise de reação da polimerase em cadeia quantitativa (qPCR) um número maior de cópias de DNA de fungos e do filo Ascomycota nos indivíduos obesos quando comparado aos indivíduos com sobrepeso e obesos. Foi verificada correlação positiva entre os fungos e os parâmetros antropométricos colesterol total, LDL, triglicerídeos, hemoglobina, HOMA-IR, HOMA-β, insulina, glicose sérica, creatinina e porcentagem de fibras e carboidratos da dieta. Outros estudos são necessários para melhor compreender a interrelação entre a micobiota do intestino e a obesidade. Futuramente, este conhecimento poderá ser utilizado na modulação da micobiota intestinal e no tratamento da obesidade.
Fungi have a complex role in the intestinal tract, directly influencing health and disease and potential dysbiosis could contribute to obesity. The aim of this study was to investigate the fungal diversity of human gut microbiota among eutrophic, overweight, and obese individuals and to understand the gut microbial ecology shifts between healthy and obese individuals. Stool samples of 72 adult individuals were collected and dependent and independent cultive approach were performed to evaluate the fungi. The yeasts were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the filamentous fungi were identified by microculture. The mean count of filamentous fungi and yeast was 1.58 log10 CFU/g of feces. Significant differences in the population level of the filamentous fungi was observed within eutrophic and obese groups. Overall, 34 genera were identified. The predominant phylum was Ascomycota with 20 different genera, followed by Basidiomycota and Zygomycota. The most prevalent specie was Paecylomyces sp. in euthrophic individuals and Penicillium sp. in obese individuals. The results of the eutrophic individuals suggest a slightly higher diversity of fungi within these individuals. Female individuals had a greater diversity of fungal types compared to males. The denaturing gradient gel electrophoresis (DGGE) analysis showed the grouping of eutrophic and overweight individuals in one cluster and of obese individuals in another cluster, although richness was low in all three groups. The fluorescence in situ hybridization (FISH) analysis showed a higher relative density of C. albicans in the obese group when compared to eutrophic and by the quantitative real time PCR (qPCR) a larger number of DNA copies of fungi and the phylum Ascomycota in obese individuals when compared to overweight and obese individuals. There was a positive correlation between fungi and the anthropometric parameters, total cholesterol, LDL, triglycerides, hemoglobin, HOMA-IR, HOMA-β, insulin, serum glucose, creatinine and percentage of dietary fibers and carbohydrates. Other studies are needed to better understand the causal relationship between gut mycobiota and obesity. This knowledge could be used in modulating the gut mycobiota and identifying future obesity treatments.