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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 Lancet. Gastroenterology &... May 2022Faecal microbiota transplantation (FMT) is an innovative approach to treat diseases that are associated with gut dysbiosis, by transferring a healthy stool microbiota to... (Review)
Review
Faecal microbiota transplantation (FMT) is an innovative approach to treat diseases that are associated with gut dysbiosis, by transferring a healthy stool microbiota to a recipient with disease. Beyond the bacteriome, the human gut also harbours diverse communities of viruses and fungi, collectively known as the virome and the mycobiome. The effect of the virome and the mycobiome on the success of FMT therapy has not been appreciated until recently. In this Review, we summarise the current literature on the effects of the gut virome and mycobiome on the treatment of various diseases with FMT. We discuss the beneficial effects and health concerns of viral and fungal transfer during FMT, and highlight the roles of bacteriophages and Candida species in FMT efficacy. We also summarise the intricate relationships between the gut virome, mycobiome, bacteriome, and host immunity underlying FMT effectiveness. Future efforts should be devoted to understanding the versatile roles and the therapeutic mechanisms of viral and fungal lineages, and their combinations, in different diseases. Harnessing the gut virome, mycobiome, and bacteriome in combination is a promising prospect for the future of FMT and microbiota-based therapies.
Topics: Dysbiosis; Fecal Microbiota Transplantation; Humans; Microbiota; Mycobiome; Virome
PubMed: 35276080
DOI: 10.1016/S2468-1253(21)00303-4 -
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 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 -
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 -
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 -
Nature Aug 2023A growing body of literature suggests that alterations in the human microbiome are causative of disease initiation and progression. Aykut et al. present data supporting...
A growing body of literature suggests that alterations in the human microbiome are causative of disease initiation and progression. Aykut et al. present data supporting the argument that alterations in the gut fungal microbiome (the “mycobiome”), along with the presence of fungal elements within pancreatic tissue (specifically those of the genus , are associated with pancreatic oncogenesis. Upon analyzing the human sequencing data presented in the original manuscript, we found few fungal reads in pancreatic tissue samples and did not identify differences in pancreatic or gut mycobiome composition between healthy and pancreatic ductal adenocarcinoma (PDAC) patients. Our re-analysis of these data does not support an association between an intrinsic pancreatic mycobiome and the development of human PDAC, and illustrates the challenges in analyzing microbiome sequencing data from low biomass samples.
Topics: Humans; Mycobiome; Pancreatic Neoplasms; Pancreas; Carcinogenesis
PubMed: 37532819
DOI: 10.1038/s41586-023-06292-1 -
Pharmacological Research Jul 2023Metabolic diseases, such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and obesity, have become a major public health problem worldwide.... (Review)
Review
Metabolic diseases, such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and obesity, have become a major public health problem worldwide. In recent years, most research on the role of gut microbes in metabolic diseases has focused on bacteria, whereas fungal microbes have been neglected. This review aims to provide a comprehensive overview of gut fungal alterations in T2DM, obesity, and NAFLD, and to discuss the mechanisms associated with disease development. In addition, several novel strategies targeting gut mycobiome and/or their metabolites to improve T2DM, obesity and NAFLD, including fungal probiotics, antifungal drugs, dietary intervention, and fecal microbiota transplantation, are critically discussed. The accumulated evidence suggests that gut mycobiome plays an important role in the occurrence and development of metabolic diseases. The possible mechanisms by which the gut mycobiome affects metabolic diseases include fungal-induced immune responses, fungal-bacterial interactions, and fungal-derived metabolites. Candida albicans, Aspergillus and Meyerozyma may be potential pathogens of metabolic diseases because they can activate the immune system and/or produce harmful metabolites. Moreover, Saccharomyces boulardii, S. cerevisiae, Alternaria, and Cochliobolus fungi may have the potential to improve metabolic diseases. The information may provide an important reference for the development of new therapeutics for metabolic diseases based on gut mycobiome.
Topics: Humans; Mycobiome; Saccharomyces cerevisiae; Gastrointestinal Microbiome; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Obesity; Bacteria
PubMed: 37244385
DOI: 10.1016/j.phrs.2023.106807 -
Current Opinion in Microbiology Oct 2023Over the past decade, our understanding of the composition and function of the human mucosal surface-associated fungal community (i.e. the mycobiome) has rapidly... (Review)
Review
Over the past decade, our understanding of the composition and function of the human mucosal surface-associated fungal community (i.e. the mycobiome) has rapidly expanded. Fungi colonize at various sites of the mucosal surface at birth and play important roles in the development and homeostasis of immune system throughout adulthood. Here, we review the recent research progresses in the human mycobiome at different body sites, including the gastrointestinal (GI) tract, the respiratory tract, the urogenital tract, the oral cavity, the skin surface, and the tumor tissues. Researchers have made extensive effort in characterizing the interactions between mycobiome and immune system, especially in the GI tract. We discuss the mycobiome dysbiosis and its implications to the progression of diseases such as inflammatory bowel diseases, alcoholic liver diseases, systemic infections, cancers, and so on, indicating the potential of mycobiome-targeting intervention strategy for life-threatening diseases.
Topics: Infant, Newborn; Humans; Adult; Mycobiome; Fungi; Inflammatory Bowel Diseases; Respiratory System
PubMed: 37527562
DOI: 10.1016/j.mib.2023.102361