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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 -
Nature Immunology Nov 2023Gastrointestinal fungal dysbiosis is a hallmark of several diseases marked by systemic immune activation. Whether persistent pathobiont colonization during immune...
Gastrointestinal fungal dysbiosis is a hallmark of several diseases marked by systemic immune activation. Whether persistent pathobiont colonization during immune alterations and impaired gut barrier function has a durable impact on host immunity is unknown. We found that elevated levels of Candida albicans immunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal Candida overgrowth, mycobiota dysbiosis and systemic neutrophilia. Analysis of hematopoietic stem cell progenitors in sCOVID-19 revealed transcriptional changes in antifungal immunity pathways and reprogramming of granulocyte myeloid progenitors (GMPs) for up to a year. Mice colonized with C. albicans patient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. sCOVID-19 patients treated with tocilizumab experienced sustained reductions in C. albicans IgG antibodies titers and GMP transcriptional changes. These findings suggest that gut fungal pathobionts may contribute to immune activation during inflammatory diseases, offering potential mycobiota-immune therapeutic strategies for sCOVID-19 with prolonged symptoms.
Topics: Humans; Animals; Mice; COVID-19; Antifungal Agents; Mycobiome; Dysbiosis; Neutrophils; Candida albicans; Immunoglobulin G
PubMed: 37872315
DOI: 10.1038/s41590-023-01637-4 -
Frontiers in Cellular and Infection... 2020Asthma is a group of inflammatory conditions that compromises the airways of a continuously increasing number of people around the globe. Its complex etiology comprises... (Review)
Review
Asthma is a group of inflammatory conditions that compromises the airways of a continuously increasing number of people around the globe. Its complex etiology comprises both genetic and environmental aspects, with the intestinal and lung microbiomes emerging as newly implicated factors that can drive and aggravate asthma. Longitudinal infant cohort studies combined with mechanistic studies in animal models have identified microbial signatures causally associated with subsequent asthma risk. The recent inclusion of fungi in human microbiome surveys has revealed that microbiome signatures associated with asthma risk are not limited to bacteria, and that fungi are also implicated in asthma development in susceptible individuals. In this review, we examine the unique properties of human-associated and environmental fungi, which confer them the ability to influence immune development and allergic responses. The important contribution of fungi to asthma development and exacerbations prompts for their inclusion in current and future asthma studies in humans and animal models.
Topics: Animals; Asthma; Fungi; Humans; Hypersensitivity; Infant; Microbiota; Mycobiome
PubMed: 33324573
DOI: 10.3389/fcimb.2020.583418 -
Science (New York, N.Y.) Jul 2022Mycobiota modulate immunity and behavior.
Mycobiota modulate immunity and behavior.
Topics: Animals; Candida; Clostridioides difficile; Clostridium Infections; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Immunity; Mice; Microbial Interactions; Mycobiome
PubMed: 35857570
DOI: 10.1126/science.abq6056 -
EBioMedicine Oct 2023Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC)...
BACKGROUND
Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC) carcinogenesis has not previously been investigated.
METHODS
We characterized the oral salivary fungal mycobiome in 476 untreated incident NPC patients and 537 population-based controls using fungal internal transcribed spacer (ITS)-2 sequencing. The relationship between oral fungal mycobiome and the risk of NPC was assessed through bioinformatic and biostatistical analyses.
FINDINGS
We found that lower fungal alpha diversity was associated with an increased odds of NPC [lower vs. higher: observed features (adjusted odds ratio [OR] = 5.81, 95% confidence interval [CI] = 3.60-9.38); Simpson diversity (1.53, 1.03-2.29); Shannon diversity (2.03, 1.35-3.04)]. We also observed a significant difference in global fungal community patterns between cases and controls based on Bray-Curtis dissimilarity (P < 0.001). Carriage of oral fungal species, specifically, Saccharomyces cerevisiae, Candida tropicalis, Lodderomyces elongisporus, Candida albicans, and Fusarium poae, was associated with significantly higher odds of NPC, with ORs ranging from 1.56 to 4.66. Individuals with both low fungal and low bacterial alpha diversity had a profoundly elevated risk of NPC.
INTERPRETATION
Our results suggest that dysbiosis in the oral mycobiome, characterized by a loss of fungal community diversity and overgrowth of several fungal organisms, is associated with a substantially increased risk of NPC.
FUNDING
This work was funded by the US National Institutes of Health, the Swedish Research Council, the High-level Talents Research Start-up Project of Fujian Medical University, and the China Scholarship Council.
Topics: Humans; Nasopharyngeal Carcinoma; Dysbiosis; Case-Control Studies; Mycobiome; Saccharomyces cerevisiae; Nasopharyngeal Neoplasms
PubMed: 37776725
DOI: 10.1016/j.ebiom.2023.104813 -
Liver International : Official Journal... Apr 2022Liver disease, a major cause of global mortality, has been associated with dysbiosis of the intestinal microbiota (bacteria, fungi, viruses, and other microbes). Studies... (Review)
Review
Liver disease, a major cause of global mortality, has been associated with dysbiosis of the intestinal microbiota (bacteria, fungi, viruses, and other microbes). Studies have associated changes in gut bacteria with pathogenesis and severity of liver disease, but the contributions of the mycobiome (the fungal populations of the gut) to health and disease have not been well studied. We review recent findings of alterations in the composition of the mycobiota in patients with liver disease and discuss the mechanisms by which these might affect pathogenesis and disease progression. Strategies to manipulate the gut mycobiota might be developed to treat or prevent liver disease.
Topics: Dysbiosis; Fungi; Gastrointestinal Microbiome; Humans; Liver Diseases; Mycobiome
PubMed: 34995410
DOI: 10.1111/liv.15160 -
American Journal of Physiology.... Aug 2021Advances in -omics analyses have tremendously enhanced our understanding of the role of the microbiome in human health and disease. Most research is focused on the... (Review)
Review
Advances in -omics analyses have tremendously enhanced our understanding of the role of the microbiome in human health and disease. Most research is focused on the bacteriome, but scientists have now realized the significance of the virome and microbial dysbiosis as well, particularly in noninfectious diseases such as cancer. In this review, we summarize the role of mycobiome in tumorigenesis, with a dismal prognosis, and attention to pancreatic ductal adenocarcinoma (PDAC). We also discuss bacterial and mycobial interactions to the host's immune response that is prevalently responsible for resistance to cancer therapy, including immunotherapy. We reported that the species associated with scalp and skin infections, colonize in human PDAC tumors and accelerate tumorigenesis via activating the C3 complement-mannose-binding lectin (MBL) pathway. PDAC tumors thrive in an immunosuppressive microenvironment with desmoplastic stroma and a dysbiotic microbiome. Host-microbiome interactions in the tumor milieu pose a significant threat in driving the indolent immune behavior of the tumor. Microbial intervention in multimodal cancer therapy is a promising novel approach to modify an immunotolerant ("cold") tumor microenvironment to an immunocompetent ("hot") milieu that is effective in eliminating tumorigenesis.
Topics: Adenocarcinoma; Animals; Carcinogenesis; Humans; Immunotherapy; Mycobiome; Pancreatic Neoplasms
PubMed: 34231392
DOI: 10.1152/ajpgi.00025.2021 -
Gut Microbes 2022Fungal communities (mycobiome) have an important role in sustaining the resilience of complex microbial communities and maintenance of homeostasis. The mycobiome remains...
Fungal communities (mycobiome) have an important role in sustaining the resilience of complex microbial communities and maintenance of homeostasis. The mycobiome remains relatively unexplored compared to the bacteriome despite increasing evidence highlighting their contribution to host-microbiome interactions in health and disease. Despite being a small proportion of the total species, fungi constitute a large proportion of the biomass within the human microbiome and thus serve as a potential target for metabolic reprogramming in pathogenesis and disease mechanism. Metabolites produced by fungi shape host niches, induce immune tolerance and changes in their levels prelude changes associated with metabolic diseases and cancer. Given the complexity of microbial interactions, studying the metabolic interplay of the mycobiome with both host and microbiome is a demanding but crucial task. However, genome-scale modelling and synthetic biology can provide an integrative platform that allows elucidation of the multifaceted interactions between mycobiome, microbiome and host. The inferences gained from understanding mycobiome interplay with other organisms can delineate the key role of the mycobiome in pathophysiology and reveal its role in human disease.
Topics: Fungi; Gastrointestinal Microbiome; Humans; Microbial Interactions; Microbiota; Mycobiome
PubMed: 36151873
DOI: 10.1080/19490976.2022.2121576