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The Lancet. Microbe Dec 2022The gut mycobiome (fungi) is a small but crucial component of the gut microbiome in humans. Intestinal fungi regulate host homoeostasis, pathophysiological and... (Review)
Review
The gut mycobiome (fungi) is a small but crucial component of the gut microbiome in humans. Intestinal fungi regulate host homoeostasis, pathophysiological and physiological processes, and the assembly of the co-residing gut bacterial microbiome. Over the past decade, accumulating studies have characterised the gut mycobiome in health and several pathological conditions. We review the compositional and functional diversity of the gut mycobiome in healthy populations from birth to adulthood. We describe factors influencing the gut mycobiome and the roles of intestinal fungi-especially Candida and Saccharomyces spp-in diseases and therapies with a particular focus on their synergism with the gut bacterial microbiome and host immunity. Finally, we discuss the underappreciated effects of gut fungi in clinical implications, and highlight future microbiome-based therapies that harness the tripartite relationship among the gut mycobiome, bacterial microbiome, and host immunity, aiming to restore a core gut mycobiome and microbiome and to improve clinical efficacy.
Topics: Humans; Adult; Mycobiome; Gastrointestinal Microbiome; Bacteria; Fungi; Microbiota
PubMed: 36182668
DOI: 10.1016/S2666-5247(22)00203-8 -
Cell Sep 2022Cancer-microbe associations have been explored for centuries, but cancer-associated fungi have rarely been examined. Here, we comprehensively characterize the cancer...
Cancer-microbe associations have been explored for centuries, but cancer-associated fungi have rarely been examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 cancer types in four independent cohorts. We report fungal DNA and cells at low abundances across many major human cancers, with differences in community compositions that differ among cancer types, even when accounting for technical background. Fungal histological staining of tissue microarrays supported intratumoral presence and frequent spatial association with cancer cells and macrophages. Comparing intratumoral fungal communities with matched bacteriomes and immunomes revealed co-occurring bi-domain ecologies, often with permissive, rather than competitive, microenvironments and distinct immune responses. Clinically focused assessments suggested prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers, and synergistic predictive performance with bacteriomes.
Topics: DNA, Fungal; Fungi; Humans; Mycobiome; Neoplasms
PubMed: 36179670
DOI: 10.1016/j.cell.2022.09.005 -
The Journal of Clinical Investigation Aug 2021The healthy lung was long thought of as sterile, but recent advances using molecular sequencing approaches have detected bacteria at low levels. Healthy lung bacteria... (Review)
Review
The healthy lung was long thought of as sterile, but recent advances using molecular sequencing approaches have detected bacteria at low levels. Healthy lung bacteria largely reflect communities present in the upper respiratory tract that enter the lung via microaspiration, which is balanced by mechanical and immune clearance and likely involves limited local replication. The nature and dynamics of the lung microbiome, therefore, differ from those of ecological niches with robust self-sustaining microbial communities. Aberrant populations (dysbiosis) have been demonstrated in many pulmonary diseases not traditionally considered microbial in origin, and potential pathways of microbe-host crosstalk are emerging. The question now is whether and how dysbiotic microbiota contribute to initiation or perpetuation of injury. The fungal microbiome and virome are less well studied. This Review highlights features of the lung microbiome, unique considerations in studying it, examples of dysbiosis in selected disease, emerging concepts in lung microbiome-host interactions, and critical areas for investigation.
Topics: Animals; Humans; Lung; Lung Diseases; Mycobiome; Virome
PubMed: 34338230
DOI: 10.1172/JCI150473 -
Virulence Apr 2017Many species of fungi have been detected in the healthy human gut; however, nearly half of all taxa reported have only been found in one sample or one study. Fungi... (Review)
Review
Many species of fungi have been detected in the healthy human gut; however, nearly half of all taxa reported have only been found in one sample or one study. Fungi capable of growing in and colonizing the gut are limited to a small number of species, mostly Candida yeasts and yeasts in the family Dipodascaceae (Galactomyces, Geotrichum, Saprochaete). Malassezia and the filamentous fungus Cladosporium are potential colonizers; more work is needed to clarify their role. Other commonly-detected fungi come from the diet or environment but either cannot or do not colonize (Penicillium and Debaryomyces species, which are common on fermented foods but cannot grow at human body temperature), while still others have dietary or environmental sources (Saccharomyces cerevisiae, a fermentation agent and sometime probiotic; Aspergillus species, ubiquitous molds) yet are likely to impact gut ecology. The gut mycobiome appears less stable than the bacterial microbiome, and is likely subject to environmental factors.
Topics: Diet; Environmental Exposure; Fungi; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Microbiota; Mycobiome
PubMed: 27736307
DOI: 10.1080/21505594.2016.1247140 -
Cell Sep 2022Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers....
Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-associated mycobiomes at up to 1 fungal cell per 10 tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of pro-inflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.
Topics: Biomarkers; Candida; DNA, Fungal; Fungi; Humans; Lung Neoplasms; Mycobiome
PubMed: 36179671
DOI: 10.1016/j.cell.2022.09.015 -
Journal of Hepatology Apr 2022Studies investigating the gut-liver axis have largely focused on bacteria, whereas little is known about commensal fungi. We characterized fecal fungi in patients with...
BACKGROUND & AIMS
Studies investigating the gut-liver axis have largely focused on bacteria, whereas little is known about commensal fungi. We characterized fecal fungi in patients with non-alcoholic fatty liver disease (NAFLD) and investigated their role in a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis.
METHODS
We performed fungal internal transcribed spacer 2 sequencing using fecal samples from 78 patients with NAFLD, 16 controls and 73 patients with alcohol use disorder. Anti-Candida albicans (C. albicans) IgG was measured in blood samples from 17 controls and 79 patients with NAFLD. Songbird, a novel multinominal regression tool, was used to investigate mycobiome changes. Germ-free mice were colonized with feces from patients with non-alcoholic steatohepatitis (NASH), fed a Western diet for 20 weeks and treated with the antifungal amphotericin B.
RESULTS
The presence of non-obese NASH or F2-F4 fibrosis was associated with a distinct fecal mycobiome signature. Changes were characterized by an increased log-ratio for Mucor sp./Saccharomyces cerevisiae (S. cerevisiae) in patients with NASH and F2-F4 fibrosis. The C. albicans/S. cerevisiae log-ratio was significantly higher in non-obese patients with NASH when compared with non-obese patients with NAFL or controls. We observed a different fecal mycobiome composition in patients with NAFLD and advanced fibrosis compared to those with alcohol use disorder and advanced fibrosis. Plasma anti-C. albicans IgG was increased in patients with NAFLD and advanced fibrosis. Gnotobiotic mice, colonized with human NASH feces and treated with amphotericin B were protected from Western diet-induced steatohepatitis.
CONCLUSIONS
Non-obese patients with NAFLD and more advanced disease have a different fecal mycobiome composition to those with mild disease. Antifungal treatment ameliorates diet-induced steatohepatitis in mice. Intestinal fungi could be an attractive target to attenuate NASH.
LAY SUMMARY
Non-alcoholic fatty liver disease is one of the most common chronic liver diseases and is associated with changes in the fecal bacterial microbiome. We show that patients with non-alcoholic fatty liver disease and more severe disease stages have a specific composition of fecal fungi and an increased systemic immune response to Candida albicans. In a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis, we show that treatment with antifungals reduces liver damage.
Topics: Animals; Feces; Gastrointestinal Microbiome; Humans; Liver; Mice; Mycobiome; Non-alcoholic Fatty Liver Disease; Saccharomyces cerevisiae
PubMed: 34896404
DOI: 10.1016/j.jhep.2021.11.029 -
Microbiome Aug 2023The fungal component of the human gut microbiome, also known as the mycobiome, plays a vital role in intestinal ecology and human health. However, the overall structure...
BACKGROUND
The fungal component of the human gut microbiome, also known as the mycobiome, plays a vital role in intestinal ecology and human health. However, the overall structure of the gut mycobiome as well as the inter-individual variations in fungal composition remains largely unknown. In this study, we collected a total of 3363 fungal sequencing samples from 16 cohorts across three continents, including 572 newly profiled samples from China.
RESULTS
We identify and characterize four mycobiome enterotypes using ITS profiling of 3363 samples from 16 cohorts. These enterotypes exhibit stability across populations and geographical locations and significant correlation with bacterial enterotypes. Particularly, we notice that fungal enterotypes have a strong age preference, where the enterotype dominated by Candida (i.e., Can_type enterotype) is enriched in the elderly population and confers an increased risk of multiple diseases associated with a compromised intestinal barrier. In addition, bidirectional mediation analysis reveals that the fungi-contributed aerobic respiration pathway associated with the Can_type enterotype might mediate the association between the compromised intestinal barrier and aging.
CONCLUSIONS
We show that the human gut mycobiome has stable compositional patterns across individuals and significantly correlates with multiple host factors, such as diseases and host age. Video Abstract.
Topics: Humans; Aged; Mycobiome; Microbiota; Gastrointestinal Microbiome; Candida; Aging
PubMed: 37563687
DOI: 10.1186/s40168-023-01586-y -
Cell Mar 2022Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies....
Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies. Yet, the mechanisms by which intestinal fungi promote homeostasis remain unclear. We characterized the mycobiota biogeography along the gastrointestinal tract and identified a subset of fungi associated with the intestinal mucosa of mice and humans. Mucosa-associated fungi (MAF) reinforced intestinal epithelial function and protected mice against intestinal injury and bacterial infection. Notably, intestinal colonization with a defined consortium of MAF promoted social behavior in mice. The gut-local effects on barrier function were dependent on IL-22 production by CD4 T helper cells, whereas the effects on social behavior were mediated through IL-17R-dependent signaling in neurons. Thus, the spatial organization of the gut mycobiota is associated with host-protective immunity and epithelial barrier function and might be a driver of the neuroimmune modulation of mouse behavior through complementary Type 17 immune mechanisms.
Topics: Animals; Fungi; Gastrointestinal Microbiome; Immunity, Mucosal; Intestinal Mucosa; Mice; Mucous Membrane; Mycobiome; Receptors, Interleukin-17; Social Behavior
PubMed: 35176228
DOI: 10.1016/j.cell.2022.01.017 -
Medical Mycology Journal 2023The human body is host to a large number of commensal microbial species such as bacteria, fungi, and viruses. Among these, the human mycobiome is often neglected as a... (Review)
Review
The human body is host to a large number of commensal microbial species such as bacteria, fungi, and viruses. Among these, the human mycobiome is often neglected as a potential cause of disease, as it is thought to be comparatively much less abundant and less diverse than the human bacteriome. Additionally, most fungi are not easily cultured, even in specific media. Hence, their study has been limited to date, mainly because of the unavailability of methods used for their detection. However, the utilization of a novel metagenomic methodology will enable the identification of well-characterized mycobiomes in several parts of the human body and broaden our knowledge of their contribution to human health and disease. In this article, we review the role of the human mycobiome in the gut, respiratory organs, skin, genital tract, and carcinogenesis, highlighting the correlations between the human mycobiome and mycobiome-associated diseases.
Topics: Humans; Mycobiome; Carcinogenesis; Knowledge; Metagenome; Metagenomics
PubMed: 37648499
DOI: 10.3314/mmj.23-002 -
Gut Sep 2022The human gut fungal community, known as the mycobiome, plays a fundamental role in the gut ecosystem and health. Here we aimed to investigate the determinants and...
OBJECTIVE
The human gut fungal community, known as the mycobiome, plays a fundamental role in the gut ecosystem and health. Here we aimed to investigate the determinants and long-term stability of gut mycobiome among middle-aged and elderly adults. We further explored the interplay between gut fungi and bacteria on metabolic health.
DESIGN
The present study included 1244 participants from the Guangzhou Nutrition and Health Study. We characterised the long-term stability and determinants of the human gut mycobiome, especially long-term habitual dietary consumption. The comprehensive multiomics analyses were performed to investigate the ecological links between gut bacteria, fungi and faecal metabolome. Finally, we examined whether the interaction between gut bacteria and fungi could modulate the metabolic risk.
RESULTS
The gut fungal composition was temporally stable and mainly determined by age, long-term habitual diet and host physiological states. Specifically, compared with middle-aged individuals, and spp were depleted, while was enriched in the elderly. Dairy consumption was positively associated with but inversely associated with . Notably, spp interacted with gut bacterial diversity to influence insulin resistance. Bidirectional mediation analyses indicated that bacterial function or faecal histidine might causally mediate an impact of on blood cholesterol.
CONCLUSION
We depict the sociodemographic and dietary determinants of human gut mycobiome in middle-aged and elderly individuals, and further reveal that the gut mycobiome may be closely associated with the host metabolic health through regulating gut bacterial functions and metabolites.
Topics: Adult; Aged; Bacteria; Ecosystem; Feces; Fungi; Gastrointestinal Microbiome; Humans; Middle Aged; Mycobiome
PubMed: 35017200
DOI: 10.1136/gutjnl-2021-326298