The gut mycobiome, the fungal component of the gut microbiota, plays a crucial role in health and disease. Although fungi represent a small fraction of the gut ecosystem, they influence immune responses, gut homeostasis, and disease progression. The mycobiome's composition varies with age, diet, and host factors, and its imbalance has been linked to conditions such as inflammatory bowel disease (IBD) and metabolic disorders. Advances in sequencing have expanded our understanding of gut fungi, but challenges remain due to methodological limitations and high variability between individuals. Emerging therapeutic strategies, including antifungals, probiotics, fecal microbiota transplantation, and dietary interventions, show promise but require further study. This review highlights recent discoveries on the gut mycobiome, its interactions with bacteria, its role in disease, and potential clinical applications. A deeper understanding of fungal contributions to gut health will help develop targeted microbiome-based therapies.

Fungi are important and often underestimated human pathogens. Infections with fungi mostly originate from the environment, from soil or airborne spores. By contrast, Candida albicans, one of the most common and clinically important fungal pathogens, permanently exists in the vast majority of healthy individuals as a member of the human mucosal microbiota. Only under certain circumstances will these commensals cause infections. However, although the pathogenic behaviour and disease manifestation of C. albicans have been at the centre of research for many years, its asymptomatic colonization of mucosal surfaces remains surprisingly understudied. In this Review, we discuss the interplay of the fungus, the host and the microbiome on the dualism of commensal and pathogenic life of C. albicans, and how commensal growth is controlled and permitted. We explore hypotheses that could explain how the mucosal environment shapes C. albicans adaptations to its commensal lifestyle, while still maintaining or even increasing its pathogenic potential.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely associated with dysbiosis of the gut microbiome, encompassing not only bacterial communities but also fungal populations. Despite the growing recognition of the gut microbiome's role in UC pathogenesis, the contribution of intestinal fungi has only recently garnered significant attention. In this review, we comprehensively examine the characteristics of intestinal fungi in both healthy individuals and UC patients, elucidating their role in disease pathogenesis and their interactions with bacterial communities. Additionally, we explore the impact of intestinal fungi on disease severity and therapeutic responses in UC. Furthermore, we evaluate the therapeutic potential of antifungal agents, probiotics, and fecal microbiota transplantation (FMT) in UC management, emphasizing the critical role of fungi in these treatment modalities. Future research should prioritize elucidating the multifunctional roles of fungi in UC pathogenesis and their implications for treatment strategies. Moreover, the identification of fungal biomarkers associated with FMT efficacy could pave the way for precision medicine approaches in FMT, offering novel insights into personalized therapeutic interventions for UC.

Pancreatic cancer, one of the most lethal malignancies, remains challenging due to late diagnosis, aggressive progression, and therapeutic resistance. Recent advances have revealed the presence of intratumoral microbiota, predominantly originating from the oral and gut microbiomes, which play pivotal roles in pancreatic cancer pathogenesis. The dynamic interplay between oral and gut microbial communities, termed the "oral-gut microbiota axis," contributes multifacetedly to pancreatic ductal adenocarcinoma (PDAC). Microbial translocation via anatomical or circulatory routes establishes tumor-resident microbiota, driving oncogenesis through metabolic reprogramming, immune regulation, inhibition of apoptosis, chronic inflammation, and dysregulation of the cell cycle. Additionally, intratumoral microbiota promote chemoresistance and immune evasion, further complicating treatment outcomes. Emerging evidence highlights microbial signatures in saliva and fecal samples as promising non-invasive diagnostic biomarkers, while microbial diversity correlates with prognosis. Therapeutic strategies targeting this axis-such as antibiotics, probiotics, and engineered bacteria-demonstrate potential to enhance treatment efficacy. By integrating mechanisms of microbial influence on tumor biology, drug resistance, and therapeutic applications, the oral-gut microbiota axis emerges as a critical regulator of PDAC, offering novel perspectives for early detection, prognostic assessment, and microbiome-based therapeutic interventions.

The majority of metagenomic studies are based on the study of bacterial biota. At the same time, the COVID-19 pandemic has prompted interest in the study of both individual fungal pathogens and fungal communities (i.e., the mycobiome) as a whole. Here, in this work, we investigated the human gut mycobiome during COVID-19. Stool samples were collected from patients at two time points: at the time of admission to the hospital (the first time point) and at the time of discharge from the hospital (the second time point). The results of this study revealed that Geotrichum sp. is more represented in a group of patients with COVID-19. Therefore, Geotrichum sp. is elevated in patients at the time of admission to the hospital and underestimated at the time of discharge. Additionally, the influence of factors associated with the diversity of fungal gut microbiota was separately studied, including disease severity and age factors.

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease that can cause reproductive disorders in sows and affect the breathing of piglets, seriously endangering pig breeding worldwide. In this study, Lactobacillus plantarum NC8 was used as the expression delivery vector of foreign proteins, and a single-chain antibody was designed based on an mAb-PN9cx3 sequence. Three recombinant strains of Lactobacillus plantarum, namely, NC8/pSIP409-pgsA'-PN9cx3-scFV(E), NC8/pSIP409-pgsA'-PN9cx3-HC(E), and NC8/pSIP409-pgsA'-PN9cx3-LC(E), were successfully constructed. In an in vitro test, the viral load of each experimental group was significantly lower than that of the control group (p < 0.01). In the piglet challenge protection test, the percentage of CD3+CD8+T cells in the blood of piglets given complex lactic acid bacteria was significantly increased before and after the challenge (p < 0.01); the body temperature of piglets in this group was normal, the viral load of each organ was reduced, and the obvious pathological changes in each tissue were alleviated. At the same time, the abundance of Bacteroides, Fusobacterium, and other bacteria in the intestinal tracts of the piglets changed, affecting the metabolism of carbohydrates and amino acids and the differentiation of Th1 and Th2 cells. This experiment provides a feasible strategy and method for the design of a PRRSV vaccine.

Intestinal fungi, collectively referred to as mycobiota, constitute a small (0.01-2%) but crucial component of the overall intestinal microbiota. While fungi are far less abundant than bacteria in the gut, the volume of an average fungal cell is roughly 100-fold greater than that of an average bacterial cell. They play a vital role in nutrient metabolism and maintaining intestinal health. The composition and spatial organization of mycobiota vary across different animal species and are influenced by a multitude of factors, including age, diet, and the host's physiological state. At present, quantitative research on the composition of mycobiota in monogastric animals remains scarce, and investigations into the mechanisms underlying their metabolic functions are also relatively restricted. This review delves into the distribution characteristics of mycobiota, including Candida albicans, Saccharomyces cerevisiae, Kazachstania slooffiae, in monogastric animals, the factors influencing their composition, and the consequent impacts on host metabolism and health. The objective is to offer insights for a deeper understanding of the nutritional significance of intestinal fungi in monogastric animals and to explore the mechanisms by which they affect host health in relation to inflammatory bowel disease (IBD), diarrhea, and obesity. Through a systematic evaluation of their functional contributions, this review shifts our perception of intestinal fungi from overlooked commensals to key components in gut ecosystem dynamics, emphasizing their potential in personalized metabolic control regulation and the enhancement of disease prevention and treatment strategies.

The disruptive effect of antibiotics on the composition and function of the human microbiota is well established. However, the hypothesis that probiotics can help restore the antibiotic-disrupted microbiota has been advanced, with little consideration of the strength of evidence supporting it. Some clinical data suggest that probiotics can reduce antibiotic-related side effects, including Clostridioides difficile-associated diarrhoea, but there are no data that causally link these clinical effects to microbiota protection or recovery. Substantial challenges hinder attempts to address this hypothesis, including the absence of consensus on the composition of a 'normal' microbiota, non-standardized and evolving microbiome measurement methods, and substantial inter-individual microbiota variation. In this Review, we explore these complexities. First, we review the known benefits and risks of antibiotics, the effect of antibiotics on the human microbiota, the resilience and adaptability of the microbiota, and how microbiota restoration might be defined and measured. Subsequently, we explore the evidence for the efficacy of probiotics in preventing disruption or aiding microbiota recovery post-antibiotic treatment. Finally, we offer insights into the current state of research and suggest directions for future research.

Behcet's syndrome, as a vasculitic disease involving multiple systems, often induces oral mucosal ulcers. However, levels of inflammatory cytokines and metabolites are unknown for the probability of developing the disease. This study aims to reveal the causal relationship between the cytokines and metabolites and Behcet's syndrome through Mendelian randomization analysis.

The instrumental variable single nucleotide polymorphisms (SNPs) were used in the study, which showed associations between 91 cytokines and 553 metabolites, respectively. To explore the causal relationship between these exposure factors and Behcet's syndrome, the random effects inverse variance weighting method was adopted. In addition, sensitivity analysis was carried out using Cochran's Q test, heterogeneity test, horizontal pleotropy test and MR-Egger intercept test to evaluate the robustness and validity of our research results.

A total of five substances were identified as causally related to Behcet's syndrome, namely, the cellular factors Interleukin 12 subunit beta(IL-12B) and Interleukin-33(IL-33), the metabolite mannitol, X-12728, and Ratio of Bisallylic groups to double bonds. Furthermore, no significant evidence suggesting heterogeneity or pleiotropy was observed.

Our study adds to current knowledge on the role of specific inflammatory cytokines and metabolites in aetiology of Behcet's syndrome. The identified cytokines and metabolites might be used as markers for clinical screening and prevention of Behcet's syndrome, as well as candidate molecules for future mechanism exploration and drug target selection. Further validation is needed to assess the potential of these cytokines and metabolites as pharmacological targets for Behcet's syndrome prevention.

Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.

The mammalian gastrointestinal tract is a stage for dynamic inter-kingdom interactions among bacteria, fungi, viruses, and protozoa, which collectively shape the gut micro-ecology and influence host physiology. Despite being a modest fraction, the fungal community, also referred to as mycobiota, represents a critical component of the gut microbiota. Emerging evidence suggests that fungi act as early colonizers of the intestine, exerting a lasting influence on gut development. Meanwhile, the composition of the mycobiota is influenced by multiple factors, with diet, nutrition, drug use (e.g., antimicrobials), and physical condition standing as primary drivers. During its establishment, the mycobiota forms both antagonistic and synergistic relationships with bacterial communities within the host. For instance, intestinal fungi can inhibit bacterial colonization by producing alcohol, while certain bacterial pathogens exploit fungal iron carriers to enhance their growth. However, the regulatory mechanisms governing these complex interactions remain poorly understood. In this review, we first introduce the methodologies for studying the microbiota, then address the significance of the mycobiota in the mammalian intestine, especially during weaning when all 'primary drivers' change, and, finally, discuss interactions between fungi and bacteria under various influencing factors. Our review aims to shed light on the complex inter-kingdom dynamics between fungi and bacteria in gut homeostasis and provide insights into how they can be better understood and managed to improve host health and disease outcomes.

Microorganisms in the soil are crucial constituents of land ecosystems, significantly influencing their structure and functionality. However, the accumulation of antibiotics in agricultural practices may negatively affect these microbial communities. The objective of this study was to explore the ecological effects of the sulfonamide drug sulfadiazine (SDZ) on the rhizosphere soil microbial communities of ryegrass (Lolium perenne L.). A potting system experiment was constructed by exposing for 45 days after treatments with different initial concentrations of SDZ (0, 1, 10, and 30 mg/kg) to assess the effects of SDZ on soil microbial diversity, bacterial-fungal co-occurrence networks, and community assembly processes. The findings indicated that SDZ treatment significantly altered the community composition, especially for bacteria in the phylum Proteobacteria and Gemmatimonadota and fungi in the phylum Mortierellomycota and Aphelidiomycota. Network analysis revealed that SDZ stress caused alterations in microbial interaction patterns, especially at high treatment concentrations, and reduced network connectivity. In addition, SDZ significantly affected microbial community assembly processes, where stochastic processes were enhanced in bacterial communities, while fungal communities showed a balance of stochastic and deterministic processes. Analysis of environmental variables revealed that the presence of SDZ may disrupt the link between soil microorganisms and soil nitrogen compounds. The results provide new perspectives for understanding the ecological impacts of antibiotic residues in agroecosystems and provide a scientific basis for soil health management.

Candida albicans gastrointestinal (GI) colonization is crucial for the onset of invasive disease. This research encompassed 31 patients diagnosed with Candida spp. bloodstream infections during their admission to a university hospital in China.

We explored risk factors associated with C. albicans GI colonization and ensuing translocated infection. Animal models were established via gavage with clinical isolates of C. albicans to induce GI tract colonization and subsequent kidney translocation infection. Our analysis is focused on 16S rRNA gene sequencing, metabolomics of colon contents, and transcriptomics of colon tissues, examining the intestinal barrier, inflammatory responses, and immune cell infiltration.

This study observed that down-regulation of programmed cell death 1 (PD-1) in colon tissues is likely linked to the progression from C. albicans colonization to translocated infection. Notably, reductions in Dubosiella abundance and Short-chain fatty acids (SCFA) levels, coupled with increases in Mucispirillum and D-erythro-imidazolylglycerol phosphate, were indicator features during the advancement to translocated invasive infection in hosts with rectal colonization by C. albicans and lower serum protein levels.

Given the similarity in intestinal bacterial communities and metabolome profiles, antifungal treatment may not be necessary for patients with nonpathogenic C. albicans colonization. The reduced expression of PD-1 in colon tissues may contribute to the transition from colonized C. albicans to subsequent translocated infection. The indicator features of decreased Dubosiella abundance and SCFA levels, coupled with increased Mucispirillum and D-erythro-imidazolylglycerol phosphate, are likely linked to the development of translocated invasive infection in hosts colonized rectally by C. albicans with lower serum protein levels.

Candida albicans invasive infections pose a significant challenge to contemporary medicine, with mortality rates from such fungal infections remaining high despite antifungal treatment. Gastrointestinal colonization by potential pathogens is a critical precursor to the development of translocated infections. Consequently, there is an increasing demand to identify clinical risk factors, multi-omics profiles, and key indicators to prevent the progression to translocated invasive infections in patients colonized rectally by C. albicans.

Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota-including bacteria, viruses, fungi, and parasites-in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the "hygiene hypothesis" suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.

As an emerging contaminant, microplastics (MPs) have received considerable attention for their potential threat to the soil environment. However, the response of soil bacterial and fungal communities to MPs exposure remains unclear. In this study, we conducted a global meta-analysis of 95 publications and 2317 observations to assess the effects of nonbiodegradable MP properties and exposure conditions on soil microbial biomass, alpha and beta diversity, and community structure. Our results indicate that MPs increased (p < 0.05) soil active microbial biomass by 42%, with the effect varying with MPs type, exposure concentration, exposure time and soil pH. MPs concentration was identified as the most important factor controlling the response of soil microbial biomass to MPs. MPs addition decreased (p < 0.05) the soil bacterial Shannon and Chao1 indices by 2% and 3%, respectively, but had limited effects (p > 0.05) on soil fungal Shannon and Chao1 indices. The type of MPs and exposure time determined the effects of MPs on bacterial Shannon and Chao1 indices, while the type of MPs and soil pH controlled the response ratios of fungal Shannon and Chao1 indices to MPs. Specifically, soil organic carbon (SOC) was the major factor regulating the response ratio of bacterial alpha diversity index to MPs. The presence of MPs did not affect soil bacterial community structure and beta diversity. Our results highlight that MPs reduced bacterial diversity and richness but increased the soil active microbial biomass, suggesting that MPs could disrupt biogeochemical cycles by promoting the growth of specific microorganisms.

The human gastrointestinal microbiome encompasses bacteria, fungi, and viruses forming complex bionetworks which, for organismal health, must be in a state of homeostasis. An important homeostatic mechanism derives from microbial competition, which maintains the relative abundance of microbial species in a healthy balance. Microbes compete for nutrients and secrete metabolites that inhibit other microbes. Short-chain fatty acids (SCFAs) are one such class of metabolites made by gut bacteria to very high levels. SCFAs are metabolised by microbes and host cells and have multiple roles in regulating cell physiology. Here, we review the mechanisms by which SCFAs regulate the fungal gut commensal Candida albicans. We discuss SCFA's ability to inhibit fungal growth, limit invasive behaviours and modulate cell surface antigens recognised by immune cells. We review the mechanisms underlying these roles: regulation of gene expression, metabolism, signalling and SCFA-driven post-translational protein modifications by acylation, which contribute to changes in acylome dynamics of C. albicans with potentially large consequences for cell physiology. Given that the gut mycobiome is a reservoir for systemic disease and has also been implicated in inflammatory bowel disease, understanding the mechanisms by which bacterial metabolites, such as SCFAs, control the mycobiome might provide therapeutic avenues.

The resident microbiota are a key component of a healthy organism. The vast majority of microbiome studies have focused on bacterial members, which constitute a significant portion of resident microbial biomass. Recent studies have demonstrated how the fungal component of the microbiota, or the mycobiome, influences mammalian biology despite its low abundance compared to other microbes. Fungi are known for their pathogenic potential, yet fungi are also prominent colonizers in healthy states, highlighting their duality. We summarize the characteristics that define the gut mycobiome across life, the factors that can impact its composition, and studies that identify mechanisms of how fungi confer health benefits. The goal of this review is to synthesize our knowledge regarding the composition and function of a healthy mycobiome with a view to inspiring future therapeutic advances.

Long-lived individuals have been extensively studied as a model to investigate the role of the gut microbiota in aging, but their gut fungi remain almost unexplored. Here, we recruited a community-dwelling cohort of 251 participants (24-108 years, including 47 centenarians) from Guangxi in China to characterize the gut mycobiome signatures. We found gut mycobiome markedly varied during aging and determined aging as a predominant factor driving these variations. For long-lived individuals, core taxa, including Penicillium and Aspergillus, were maintained and Candida enterotype was enriched when compared with old counterparts. Individuals with this enterotype were more likely to possess Bacteroides enterotype enriched in young and centenarians. Moreover, the drivers from Candida enterotype were positively linked with the bacteria components dominated in Bacteroides enterotype. We also identified potentially beneficial yeasts-enriched features to differentiate long-lived individuals from others. Our findings suggest that the gut mycobiome develops with aging, and long-lived individuals possess unique fungal signatures.

Candida species primarily exist as harmless commensals in the gastrointestinal tract of warm-blooded animals. However, they can also cause life-threatening infections, which are often associated with gut microbial dysbiosis. Identifying the microbial actors that restrict Candida to commensalism remains a significant challenge. In vitro models could enable a mechanistic study of the interactions between Candida and simulated colon microbiomes. Therefore, this study aimed to elucidate the spatial and temporal colonization kinetics of specific Candida, including C. albicans, C. tropicalis, and C. parapsilosis, and their relative Nakaseomyces glabratus, by using an adapted SHIME® model, simulating the ileum, and proximal and distal colons. We monitored fungal and bacterial colonization kinetics under conditions of eubiosis (commensal lifestyle) and antibiotic-induced dysbiosis (pathogenic lifestyle). Our findings highlighted the variability in the colonization potential of Candida species across different intestinal regions. The ileum compartment proved to be the most favourable environment for C. albicans and C. parapsilosis under conditions of eubiosis. Antibiotic-induced dysbiosis resulted in resurgence of opportunistic Candida species, especially C. tropicalis and C. albicans. Future research should focus on identifying specific bacterial species influencing Candida colonization resistance and explore the long-term effects of antibiotics on the mycobiome and bacteriome.

The gastrointestinal tract contains a diverse microbiome consisting of bacteria, fungi, viruses and archaea. Although these microbes usually reside as commensal organisms, it is now well established that higher abundance of specific bacterial or fungal species, or loss of diversity in the microbiome can significantly affect development, progression and outcomes in disease. Studies have mainly focused on the effects of bacteria, however, the impact of other microbes, such as fungi, has received increased attention in the last few years. Fungi only represent around 0.1% of the total gut microbial population. However, key fungal taxa such as Candida, Aspergillus and Wallemia have been shown to significantly impact health and disease. The composition of the gut mycobiome has been shown to affect immunity at distal sites, such as the heart, lung, brain, pancreas, and liver. In the case of the lung this phenomenon is referred to as the 'gut-lung axis'. Recent studies have begun to explore and unveil the relationship between gut fungi and lung immunity in diseases such as asthma and lung cancer, and lung infections caused by viruses, bacteria and fungi. In this review we will summarize the current, rapidly growing, literature describing the impact of the gut mycobiome on respiratory disease and infection.

The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking.

In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn's disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models.

Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract.

In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.

Considering the significant burden of post-acute COVID-19 conditions among patients infected with SARS-CoV-2, we aimed to identify the risk of acute respiratory complications or post-acute respiratory sequelae. A binational population-based cohort study was conducted to analyze the risk of acute respiratory complications or post-acute respiratory sequelae after SARS-CoV-2 infection. We used a Korean nationwide claim-based cohort (K-COV-N; n = 2,312,748; main cohort) and a Japanese claim-based cohort (JMDC; n = 3,115,606; replication cohort) after multi-to-one propensity score matching. Among 2,312,748 Korean participants (mean age, 47.2 years [SD, 15.6]; 1,109,708 [48.0%] female), 17.1% (394,598/2,312,748) were infected with SARS-CoV-2. The risk of acute respiratory complications or post-acute respiratory sequelae is significantly increased in people with SARS-CoV-2 infection compared to the general population (acute respiratory complications: HR, 8.06 [95% CI, 6.92-9.38]; post-acute respiratory sequelae: 1.68 [1.62-1.75]), and the risk increased with increasing COVID-19 severity. We identified COVID-19 vaccination as an attenuating factor, showing a protective association against acute or post-acute respiratory conditions. Furthermore, while the excess post-acute risk diminished with time following SARS-CoV-2 infection, it persisted beyond 6 months post-infection. The replication cohort showed a similar pattern in the association. Our study comprehensively evaluates respiratory complications in post-COVID-19 conditions, considering attenuating factors such as vaccination status, post-infection duration, COVID-19 severity, and specific respiratory conditions.

Fungi inhabit different anatomic sites in the human body. Advances in omics analyses of host‑microbiome interactions have tremendously improved our understanding of the effects of fungi on human health and diseases such as tumors. Due to the significant enrichment of specific fungi in patients with malignant tumors, the associations between fungi and human cancer have attracted an increasing attention in recent years. Indeed, cancer type‑specific fungal profiles have been found in different tumor tissues. Importantly, fungi also influence tumorigenesis through multiple factors, such as host immunity and bioactive metabolites. Microbiome interactions, host factors and fungal genetic and epigenetic factors could be involved in fungal enrichment in tumor tissues and/or in the conversion from a commensal fungus to a pathogenic fungus. Exploration of the interactions of fungi with the bacterial microbiome and the host may enable them to be a target for cancer diagnosis and treatment. In the present review, the associations between fungi and human cancer, cancer type‑specific fungal profiles and the mechanisms by which fungi cause tumorigenesis were discussed. In addition, possible factors that can lead to the enrichment of fungi in tumor tissues and/or the conversion of commensal fungi to pathogenic fungi, as well as potential therapeutic and preventive strategies for tumors based on intratumoral fungi were summarized.

The nasal cavity is the initial site of the human respiratory tract and is one of the habitats where microorganisms colonize. The findings from a growing number of studies have shown that the nasal microbiome is an important factor for human disease and health. 16S rRNA sequencing and metagenomic next-generation sequencing (mNGS) are the most commonly used means of microbiome evaluation. Among them, 16S rRNA sequencing is the primary method used in previous studies of nasal microbiomes. However, neither 16S rRNA sequencing nor mNGS can be used to analyze the genes specifically expressed by nasal microorganisms and their functions. This problem can be addressed by proteomic analysis of the nasal microbiome.

In this review, we summarize current advances in research on the nasal microbiome, introduce the methods for proteomic evaluation of the nasal microbiome, and focus on the important roles of proteomic evaluation of the nasal microbiome in the diagnosis and treatment of related diseases.

The detection method for microbiome-expressed proteins is known as metaproteomics. Metaproteomic analysis can help us dig deeper into the nasal microbiomes and provide new targets and ideas for clinical diagnosis and treatment of many nasal dysbiosis-related diseases.

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.

The health benefits of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are linked to their regulatory effects on the composition of the gut microbiota. However, there is a lack of direct evidence on whether omega-3 PUFAs regulate the gut microbial homeostasis under physiological conditions. This study investigated the impact of equivalent doses of EPA, DHA, and fish oil (FO) with a DHA to EPA ratio of approximately 1:1 on the bacterial and fungal composition of normal young mice. This study also analyzed changes in key components of the gut microenvironment, including the colonic mucus barrier and short-chain fatty acids, to address the prebiotic potential of omega-3 PUFAs. The results showed that all three omega-3 PUFAs interventions induced significant fluctuations in the gut bacteria and fungi, leading to an increase in the abundance of some probiotics. Notably, DHA, EPA, and FO interventions significantly increased the abundance of the probiotic Lactobacillus, Bifidobacterium, and Akkermansia, respectively. Both DHA and fish oil interventions also significantly reduced the abundance of potentially pathogenic fungi, such as Aspergillus and Penicillium. Association analysis of the top 19 differential fungal and bacterial genera in abundance revealed a much more bacteria-bacteria and bacteria-fungi connections, but fewer fungi-fungi connections. This highlights the importance of bacteria in the gut microecological network. Furthermore, the levels of butyric acid and valeric acid in the colonic contents of DHA intervention group were significantly increased, and the colonic mucus layer thickness was increased in three treatment groups. In summary, DHA, EPA and FO interventions showed targeted enhancement of different probiotics and enhanced colon defense barrier (mucus barrier), showing potential prebiotic effects.

Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases.

We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics.

Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years.

Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.

Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of food-borne infection in humans. Yet to be cultured Campylobacter spp. contribute to the total burden in diarrheal disease in children living in LMIC thus hampering interventions. We performed microbiome profiling and metagenomic genome assembly on samples collected from over 100 infant rhesus macaques longitudinally and during cases of clinical diarrhea within the first year of life. Acute diarrhea was associated with long-lasting taxonomic and functional shifts of the infant gut microbiome indicative of microbiome immaturity. We constructed 36 Campylobacter metagenomic assembled genomes (MAGs), many of which fell within 4 yet to be cultured species. Finally, we compared the uncultured Campylobacter MAGs assembled from infant macaques with publicly available human metagenomes to show that these uncultured species are also found in human fecal samples from LMIC. These data highlight the importance of unculturable Campylobacter spp. as an important target for reducing disease burden in LMIC children.

The gut mycobiome significantly affects host health and immunity. However, most studies have focused on symbiotic bacteria in the gut microbiome, whereas less attention has been given to symbiotic fungi. Although fungi constitute only 0.01%-0.1% of the gut microbiome, their larger size and unique immunoregulatory functions make them significant. Factors like diet, antimicrobials use, and age can disrupt the fungal community, leading to dysbiosis. Fungal-bacterial-host immune interactions are critical in maintaining gut homeostasis, with fungi playing a role in mediating immune responses such as Th17 cell activation. This review highlights methods for studying gut fungi, the composition and influencing factors of the gut mycobiome, and its potential in therapeutic interventions for intestinal and hepatic diseases. We aim to provide new insights into the underexplored role of gut fungi in human health.

The role of gut fungal species in tumor-related processes remains largely unexplored, with most studies still focusing on fungal infections. This review examines the accumulating evidence suggesting the involvement of commensal and pathogenic fungi in cancer biological process, including oncogenesis, progression, and treatment response. Mechanisms explored include fungal influence on host immunity, secretion of bioactive toxins/metabolites, interaction with bacterial commensals, and migration to other tissues in certain types of cancers. Attempts to utilize fungal molecular signatures for cancer diagnosis and fungal-derived products for treatment are discussed. A few studies highlight fungi's impact on the responsiveness and sensitivity to chemotherapy, radiotherapy, immunotherapy, and fecal microbiota transplant. Given the limited understanding and techniques in fungal research, the studies on gut fungi are still facing great challenges, despite having great potentials.

Knee synovitis is a highly prevalent and potentially curable condition for knee pain; however, its pathogenesis remains unclear. We sought to assess the associations of the gut fungal microbiota and the fungi-bacteria correlation network with knee synovitis.

Participants were derived from a community-based cross-sectional study. We performed an ultrasound examination of both knees. A knee was defined as having synovitis if its synovium was ≥4 mm and/or Power Doppler (PD) signal was within the knee synovium area (PD synovitis). We collected faecal specimens from each participant and assessed gut fungal and bacterial microbiota using internal transcribed spacer 2 and shotgun metagenomic sequencing. We examined the relation of α-diversity, β-diversity, the relative abundance of taxa and the interkingdom correlations to knee synovitis.

Among 977 participants (mean age: 63.2 years; women: 58.8%), 191 (19.5%) had knee synovitis. β-diversity of the gut fungal microbiota, but not α-diversity, was significantly associated with prevalent knee synovitis. The fungal genus Schizophyllum was inversely correlated with the prevalence and activity (ie, control, synovitis without PD signal and PD synovitis) of knee synovitis. Compared with those without synovitis, the fungi-bacteria correlation network in patients with knee synovitis was smaller (nodes: 93 vs 153; edges: 107 vs 244), and the average number of neighbours was fewer (2.3 vs 3.2).

Alterations of gut fungal microbiota and the fungi-bacteria correlation network are associated with knee synovitis. These novel findings may help understand the mechanisms of the gut-joint axis in knee synovitis and suggest potential targets for future treatment.

The microbiota shapes host biology in numerous ways. One example is protection against pathogens, which is likely critical for host fitness in consideration of the ubiquity of pathogens. The host itself can affect abundance of microbiota or pathogens, which has usually been characterized in separate studies. To date, however, it is unclear how the host influences the interaction with both simultaneously and how this triangular interaction determines fitness of the host-microbe assemblage, the so-called metaorganism. To address this current knowledge gap, we focused on a triangular model interaction, consisting of the nematode Caenorhabditis elegans, its protective symbiont Pseudomonas lurida MYb11 and its pathogen Bacillus thuringiensis Bt679. We combined the two microbes with C. elegans mutants with altered immunity and/or microbial colonization, and found that (i) under pathogen stress, immunocompetence has a larger influence on metaorganism fitness than colonization with the protective microbe; (ii) in almost all cases, MYb11 still improves fitness; and (iii) disruption of p38 MAPK signalling, which contributes centrally to immunity against Bt679, completely reverses the protective effect of MYb11, which further reduces nematode survival and fitness upon infection with Bt679. Our study highlights the complex interplay between host, protective microbe and pathogen in shaping metaorganism biology.

Aim: The bacterial microbiota is well-recognized for its role in Clostridioides difficile colonization and infection, while fungi and yeasts remain understudied. The aim of this study was to analyze the predictive value of the mycobiota and its interactions with the bacterial microbiota in light of C. difficile colonization and infection. Methods: The mycobiota was profiled by ITS2 sequencing of fecal DNA from C. difficile infection (CDI) patients (n = 29), asymptomatically C. difficile colonization (CDC) patients (n = 38), and hospitalized controls with C. difficile negative stool culture (controls; n = 38). Previously published 16S rRNA gene sequencing data of the same cohort were used additionally for machine learning and fungal-bacterial network analysis. Results: CDI patients were characterized by a significantly higher abundance of Candida spp. (MD 0.270 ± 0.089, P = 0.002) and Candida albicans (MD 0.165 ± 0.082, P = 0.023) compared to controls. Additionally, they were deprived of Aspergillus spp. (MD -0.067 ± 0.026, P = 0.000) and Penicillium spp. (MD -0.118 ± 0.043, P = 0.000) compared to CDC patients. Network analysis revealed a positive association between several fungi and bacteria in CDI and CDC, although the analysis did not reveal a direct association between Clostridioides spp. and fungi. Furthermore, the microbiota machine learning model outperformed the models based on the mycobiota and the joint microbiota-mycobiota model. The microbiota classifier successfully distinguished CDI from CDC [Area Under the Receiver Operating Characteristic (AUROC) = 0.884] and CDI from controls (AUROC = 0.905). Blautia and Bifidobacterium were marker genera associated with CDC patients and controls. Conclusion: The gut mycobiota differs between CDI, CDC, and controls and may affect Clostridioides spp. through indirect interactions. The mycobiota data alone could not successfully discriminate CDC from controls or CDI patients and did not have additional predictive value to the bacterial microbiota data. The identification of bacterial marker genera associated with CDC and controls warrants further investigation.

In silico and experimental approaches have allowed an ever-growing understanding of the interactions within the microbiota. For instance, recently acquired data have increased knowledge of the mechanisms that support, in the gut and vaginal microbiota, the resistance to colonization by Candida albicans, an opportunistic fungal pathogen whose overgrowth can initiate severe infections in immunocompromised patients. Here, we review how bacteria from the microbiota interact with C. albicans. We show how recent OMICs-based pipelines, using metagenomics and/or metabolomics, have identified bacterial species and metabolites modulating C. albicans growth. We finally discuss how the combined use of cutting-edge OMICs-based and experimental approaches could provide new means to control C. albicans overgrowth within the microbiota and prevent its consequences.

Cancer tissues harbor a large microbiome. There is growing evidence that the tumor microbiome is significantly correlated with the prognosis of cancer patients, but the exact underlying mechanisms have remained elusive. Although the tumor mycobiome is less abundant than the biome of bacteria, it is prevalent in most cancers in humans. The present review describes in detail the impact of the tumor mycobiome on cancer pathogenesis. The tumor mycobiome promotes tumor progression and metastasis by affecting the human immune system, maintaining a pro-inflammatory environment, producing aflatoxins, attenuating cell adhesion mechanisms and fungal-bacterial interactions. Furthermore, the tumor mycobiome likewise has great potential for cancer prevention, diagnosis and treatment.

While the fungus Candida albicans is a common colonizer of healthy humans, it is also responsible for mucosal infections and severe invasive disease. Understanding the mechanisms that allow C. albicans to exist as both a benign commensal and as an invasive pathogen have been the focus of numerous studies, and recent findings indicate an important role for cross-kingdom interactions on C. albicans biology. This review highlights how C. albicans-bacteria interactions influence healthy polymicrobial community structure, host immune responses, microbial pathogenesis, and how dysbiosis may lead to C. albicans infection. Finally, we discuss how cross-kingdom interactions represent an opportunity to identify new antivirulence compounds that target fungal infections.

Candida albicans is a commensal yeast present in the gut of most healthy individuals but with highly variable concentrations. However, little is known about the host factors that influence colonization densities. We investigated how microbiota, host lifestyle factors, and genetics could shape C. albicans intestinal carriage in 695 healthy individuals from the Milieu Intérieur cohort. C. albicans intestinal carriage was detected in 82.9% of the subjects using quantitative PCR. Using linear mixed models and multiway-ANOVA, we explored C. albicans intestinal levels with regard to gut microbiota composition and lifestyle factors including diet. By analyzing shotgun metagenomics data and C. albicans qPCR data, we showed that Intestinimonas butyriciproducens was the only gut microbiota species whose relative abundance was negatively correlated with C. albicans concentration. Diet is also linked to C. albicans growth, with eating between meals and a low-sodium diet being associated with higher C. albicans levels. Furthermore, by Genome-Wide Association Study, we identified 26 single nucleotide polymorphisms suggestively associated with C. albicans colonization. In addition, we found that the intestinal levels of C. albicans might influence the host immune response, specifically in response to fungal challenge. We analyzed the transcriptional levels of 546 immune genes and the concentration of 13 cytokines after whole blood stimulation with C. albicans cells and showed positive associations between the extent of C. albicans intestinal levels and NLRP3 expression, as well as secreted IL-2 and CXCL5 concentrations. Taken together, these findings open the way for potential new interventional strategies to curb C. albicans intestinal overgrowth.