Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome. Understanding these changes in the predisease phase provides a means of predicting IBD in high-risk populations and offers insights into possible mechanisms involved in disease pathogenesis. Finally, we discuss strategies to use this information to design interventions aimed at modulating the microbiome as a means of preventing or delaying the onset of IBD.

Dental caries arise from intricate interactions among oral microorganisms, impacting ecological stability and disease progression. In this study, we aimed to investigate the microbial diversity and inter-kingdom interactions in severe early childhood caries (S-ECC) and assess the influence of environmental factors such as salivary pH and trace elements. We analyzed 61 children aged 3-4 years with complete deciduous dentition, evaluating salivary pH, buffering capacity, and trace elements (iron, fluoride). We examined the performance of 16S rRNA V1-V9 regions gene and internal transcribed spacer (ITS) primers for bacteria and fungi from plaque and saliva to characterize community compositions and diversity. Findings revealed significant shifts in bacterial diversity in S-ECC saliva samples, marked by decreased diversity and elevated abundance of cariogenic species, particularly Streptococcus mutans. Candida albicans was notably more prevalent in the S-ECC group, implicating its potential role in pathogenesis. Iron and fluoride concentrations showed no significant correlation with microbial community structure. Network analyses uncovered complex intra- and inter-kingdom interactions, underscoring cooperative and competitive dynamics. S-ECC children exhibited higher abundances of bacteria (Streptococcus mutans, Granulicatella, Actinomyces) and fungi (Candida albicans), with specific microbial taxa associated with reduced salivary pH.

This study illuminates the intricate relationship between bacteria and fungi within the oral microbial community of children, specifically highlighting differences between those with S-ECC and those without caries. Through an extensive analysis of the microbial composition in both saliva and dental plaque, we identified a significant increase in the abundance of specific bacterial taxa (e.g., S. mutans, Granulicatella, Actinomyces) and fungal species (e.g., C. albicans) in the oral cavities of children with S-ECC. This finding underscores the potential role of these microorganisms in the development of caries. Contrary to previous studies that emphasize the importance of iron and fluoride in oral health, our research found no significant correlation between the concentrations of these elements and the composition of oral microbial communities. This result challenges conventional understanding and opens new avenues for future research. Additionally, our findings revealed an association between Veillonella sp., Propionibacterium sp., and Candida sp. and reduced salivary pH. This provides novel insights into the relationship between the oral microenvironment and caries development. The implications of our findings are substantial for the development of prevention and intervention strategies targeting childhood caries. They also underscore the critical need for a deeper exploration of oral microbial interactions and their environmental influences.

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease that seriously affects the quality of life of patients around the world. It is characterized by recurrent abdominal pain, diarrhea, and mucous bloody stools. There is an urgent need for more accurate diagnosis and effective treatment of IBD. Accumulated evidence suggests that gut microbiota plays an important role in the occurrence and development of gut inflammation. However, most studies on the role of gut microbiota in IBD have focused on bacteria, while fungal microorganisms have been neglected. Fungal dysbiosis can activate the host protective immune pathway related to the integrity of the epithelial barrier and release a variety of pro-inflammatory cytokines to trigger the inflammatory response. Dectin-1, CARD9, and IL-17 signaling pathways may be immune drivers of fungal dysbacteriosis in the development of IBD. In addition, fungal-bacterial interactions and fungal-derived metabolites also play an important role. Based on this information, we explored new strategies for IBD treatment targeting the intestinal fungal group and its metabolites, such as fungal probiotics, antifungal drugs, diet therapy, and fecal microbiota transplantation (FMT). This review aims to summarize the fungal dysbiosis and pathogenesis of IBD, and provide new insights and directions for further research in this emerging field.

SUMMARYThe human microbiome, including bacteria, fungi, archaea, and viruses, is intimately linked to both health and disease. The relationship between bacteria and disease has received much attention and intensive investigation, while that of the fungal microbiome, also known as mycobiome, has lagged far behind bacteria. There is growing evidence showing mycobiome dysbiosis in cancer patients, and certain cancer-specific fungi may contribute to cancer progression by interacting with both host and bacteria. It was also demonstrated that the role of fungi-derived products in cancer should also not be underestimated. Therefore, investigating how fungal pathogenesis contributes to the onset and spread of cancer would yield crucial information for cancer diagnosis, prevention, and anti-cancer therapy.

Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.

The intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host-microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host-microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ-free and gnotobiotic mouse technology, in which causal disease-driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease-driving mechanisms can be dissected. A better understanding of the health-modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ-free and gnotobiotic experiments, including considerations around germ-free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research.

Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are gastrointestinal disorders, which can be triggered by gut microbiota dysbiosis. The development of IBS-like symptoms has been linked to the overgrowth of Candida spp. In addition, the critical role of fungi has been highlighted in the pathogenesis of IBD. This study investigated the association between Blastocystis and selected yeasts in IBS and IBD patients.

This investigation is a cross-sectional study from 2022 to 2024, performed on 91 participants, including 20 healthy individuals, 27 patients with IBS, and 44 IBD patients [39 with ulcerative colitis (UC; 88.63%) and 5 (11.37%) Crohn's disease (CD)], who were also categorized based on the presence of Blastocystis. Total DNA was extracted from stool samples, and the presence and quantity of yeasts including C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, C. krusei, Geotrichum candidum, Rhodotorula spp., Cryptococcus neoformans, and Saccharomyces cerevisiae were evaluated by real-time PCR. Statistical tests were used to assess significant associations between variables.

Saccharomyces cerevisiae and C. albicans were the most prevalent yeasts in all groups. Candida tropicalis and C. neoformans were identified in neither patients nor healthy subjects. The presence/absence of C. albicans was not significantly different between patients with IBD, IBS, and the control groups. This was similar for G. candidum. However, there was a difference in the presence of S. cerevisiae among patients, although it was insignificant (p-value = 0.077). There was a significant difference in the quantity of C. albicans between IBD (880.421 ± 2140.504), IBS (10.307 ± 15.206), and controls (2875.888 ± 8383.889) (p-value = 0.020). Specifically, the source of difference was seen between IBD patients and the control group (p-value = 0.005). In addition, considering the presence of Blastocystis, a statistically significant association was seen between the number of C. albicans and the sample groups (p-value = 0.013). The quantity of C. albicans was significantly different between IBS and IBD patients.

Regarding the presence of Blastocystis, the quantity of C. albicans and S. cerevisiae was increased and decreased in the studied groups, respectively. This is a preliminary study, and eukaryote-eukaryote association in IBS and IBD patients should be considered in further studies.

Understanding the gut mycobiota composition and its impact on health requires reliable methods for fungal community assessment. This study explores the influence of DNA extraction methods in GM analysis. Three protocols were evaluated: Qiagen DNeasy blood and tissue kit with mechanical glass bead lysis (DNgb), Thermofisher MagMax Microbiome ultra-nucleic isolation kit automated method (MM), and MM combined with glass beads lysis (MMgb). Fecal samples from healthy volunteers were collected, DNA extracted and ITS2 amplicon library preparation and sequencing performed. Results showed that DNA yields did not significantly differ among methods and the addition of glass bead beating favored the recovery of DNA more appropriate for fungal analysis. Beta diversity revealed distinct clusters, with MMgb showing the most pronounced variation in mycobiota composition, exposing particularly the low abundance taxa. LEfSe analysis identified significant differences in the abundance of fungal species among the extraction methods. Samples extracted with bead beating were enriched in filamentous species, while those without this step showed higher relative abundance of yeast fungi. This study underscores the importance of selecting appropriate DNA extraction methods for accurate characterization of the gut mycobiota, emphasizing the need for standardized methodologies to ensure reproducibility and reliability in microbial data acquisition.

The gastrointestinal tract has remarkable capacity to withstand considerable insults from exposure to abrasive food particles, chemicals, allergens, and pathogenic microbes. Maintaining a robust epithelial barrier sequesters these potentially harmful substances in the lumen, preventing absorption into the systemic circulation. Normal functioning of this barrier is central in diverse physiological processes including digestion, immunity, inflammation, and gut-brain signaling. One crucial component of the barrier is the mucus layer covering the epithelium. There is increased appreciation of the importance of mucus in maintenance of the gut barrier, and how dysregulation of the mucus layer contributes to several common gastrointestinal pathologies. This manuscript reviews the physical and chemical properties of mucus, its maintenance and turnover, and its role in maintaining gut barrier integrity. The dynamic interactions of the mucus layer within the gut ecosystem are illustrated by highlighting how a weakened mucus layer or defective mucus production facilitate pathogenic microbial colonization and mucosal biofilm formation. These may potentially contribute to the pathogenesis of gastrointestinal diseases such as inflammatory bowel diseases or result in secretion and mucosal damage and inflammation in bile acid diarrhea. A final goal is to review how certain dietary factors, especially low-fiber diets and emulsifiers common in Western diets, can harm the mucus layer. This report summarizes evidence from preclinical and human studies that document damage to the mucus layer, and reviews approaches, including diets and probiotics, that promote a healthy mucus layer and break down pathogenic biofilms, thereby potentially preventing and/or treating gastrointestinal diseases that impact mucosal integrity.

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.

Melatonin (MT) (N-acetyl-5-methoxytryptamine) is an indoleamine recognized primarily for its crucial role in regulating sleep through circadian rhythm modulation in humans and animals. Beyond its association with the pineal gland, it is synthesized in various tissues, functioning as a hormone, tissue factor, autocoid, paracoid, and antioxidant, impacting multiple organ systems, including the gut-brain axis. However, the mechanisms of extra-pineal MT production and its role in microbiota-host interactions remain less understood. This review provides a comprehensive overview of MT, including its production, actions sites, metabolic pathways, and implications for human health. The gastrointestinal tract is highlighted as an additional source of MT, with an examination of its effects on the intestinal microbiota. This review explores whether the microbiota contributes to MT in the intestine, its relationship to food intake, and the implications for human health. Due to its impacts on the intestinal microbiota, MT may be a valuable therapeutic agent for various dysbiosis-associated conditions. Moreover, due to its influence on intestinal MT levels, the microbiota may be a possible therapeutic target for treating health disorders related to circadian rhythm dysregulation.

The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn's disease (CD), where microbiome dysregulation can alter immune responses, leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of a recently developed probiotic + amylase blend in the SAMP1/YitFc (SAMP) mouse model of CD-like ileitis. Four groups of SAMP mice were gavaged for 56 days with the following treatments: 1) probiotic strains + amylase (0.25 mg/100 µL PBS); 2) only probiotics; 3) only amylase; PBS-treated controls. Ilea were collected for GeoMx Digital Spatial Profiler (DSP) analysis and histological evaluation. Histology assessment for inflammation indicated a significantly reduced level of ileitis in mice administered the probiotics + amylase blend. DSP analysis showed decreased abundance of neutrophils and increased abundance of dendritic cells, regulatory T cells, and macrophages, with a significant enrichment of five intracellular pathways related to apoptosis, in probiotics + amylase-treated mice. Increased apoptosis occurrence was confirmed by (TdT)- deoxyuridine triphosphate (dUTP)-biotin nick end labeling assay. Our data demonstrate a beneficial role of the probiotic and amylase blend, highlighting an increased apoptosis of innate immunity-associated cell subsets, thus promoting the resolution of inflammation. Hence, we suggest that the developed probiotic enzyme blend may be a therapeutic tool to manage CD and therefore is a candidate formulation to be tested in clinical trials.

This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology, delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease (CD). Insights were gained from fecal microbiota transplantation (FMT) in mouse models, revealing the intricate interplay between the gut microbiota, mesenteric adipose tissue (MAT), and creeping fat. The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD; moreover, through the FMT mouse model, it observed the impact of samples from healthy patients and those with CD on symptoms. The pathogenesis of CD is complex, and its etiology remains unclear; however, it is widely believed that gut microbiota dysbiosis plays a significant role. Recently, with the development and application of next-generation sequencing technology, research on the role of fungi in the pathogenesis and chronicity of CD has deepened. This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.

This article employs bibliometric methods and visual maps to delineate the research background, collaborative relationships, hotspots, and trends in the study of gut fungi in human diseases and health.

Publications related to human gut fungi were retrieved from the Web of Science Core Collection. VOSviewer, CiteSpace, R software and Microsoft Excel were employed to generate visual representations illustrating the contributions made by countries/regions, authors, organizations, and journals. Employing VOSviewer and CiteSpace, we conducted a comprehensive analysis of the retrieved publications, revealing underlying tendencies, research hotspots, and intricate knowledge networks.

This study analyzed a total of 3,954 publications. The United States ranks first in the number of published papers and has the highest number of citations and h-index. Mostafa S Elshahed is the most prolific author. The University of California System is the institution that published the most papers. Frontiers In Microbiology is the journal with the largest number of publications. Three frequently co-cited references have experienced a citation burst lasting until 2024.

Advancements in sequencing technologies have intensified research into human gut fungi and their health implications, shifting the research focus from gut fungal infections towards microbiome science. Inflammatory bowel diseases and Candida albicans have emerged as pivotal areas of interest in this endeavor. Through this study, we have gained a deeper insight into global trends and frontier hotspots within this field, thereby enhancing our understanding of the intricate relationship between gut fungi and human health.

Gut microbiota is an intricate microbial community containing bacteria, fungi, viruses, archaea, and protozoa, and each of them contributes to diverse aspects of host health. Nevertheless, the influence of interaction among gut microbiota on host health remains uncovered. Here, we showed that the interaction between intestinal fungi and bacteria shaped lung inflammation during infection. Specifically, antifungal drug-induced dysbiosis of gut mycobiota enhanced lung inflammation during infection. Dysbiosis of gut mycobiota led to gut Escherichia coli (E. coli) overgrowth and translocation to the lung during infection, which induced lung accumulation of the CD45+F4/80+Ly6G-Ly6C-CD11b+CD11c+ macrophages. Clearance of macrophages or deletion of TLR4 (Toll-like receptor 4, recognition of LPS) rather than Dectin-1 (recognition of beta-1,3/1,6 glucans on fungi) blocked the antifungal drug-induced aggravation of lung inflammation during infection. These findings suggest that the interaction between intestinal mycobiota and commensal bacteria affects host health through the gut-lung axis, offering a potential therapeutic target for ameliorating lung inflammation during infection.

The gut microbiota plays a critical role in immune system function, with dysbiosis linked to systemic inflammation, contributing to conditions like psoriasis and depression. Although biological treatments for severe psoriasis are known to impact gut bacteria, less is understood about their effects on fungi. This study aims to investigate fungal gut microbiota changes in psoriasis patients transitioning from TNF-α inhibitors to brodalumab. Fecal samples from 20 patients were analyzed using Illumina MiSeq sequencing of the ITS2 region of 18S rRNA. Microbial diversity was assessed through Bray-Curtis dissimilarity and the Shannon-Wiener index. Clinical outcomes were measured using clinical scores for psoriasis and depression severity, with statistical analysis performed via Wilcoxon signed-rank tests and PERMANOVA. Results showed that Ascomycota was the dominant fungal phylum in both treatment groups, with Saccharomyces, Penicillium, Candida, and Debaryomyces as prevalent genera. No significant changes occurred at the phylum level after switching to brodalumab, though minor genome-level variations were observed. Beta diversity analysis highlighted inter-patient variability, with no significant correlation between fungal composition and clinical outcomes. Despite improved clinical scores, the fungal gut microbiota remained largely stable, suggesting that brodalumab does not significantly alter fungal communities in psoriasis patients. Further research is needed for a comprehensive understanding.

Autism Spectrum Disorder (ASD) is a multifactorial disorder involving genetic and environmental factors leading to pathophysiologic symptoms and comorbidities including neurodevelopmental disorders, anxiety, immune dysregulation, and gastrointestinal (GI) abnormalities. Abnormal intestinal permeability has been reported among ASD patients and it is well established that disturbances in eating patterns may cause gut microbiome imbalance (i.e., dysbiosis). Therefore, studies focusing on the potential relationship between gut microbiota and ASD are emerging. We compared the intestinal bacteriome and mycobiome of a cohort of ASD subjects with their non-ASD siblings. Differences between ASD and non-ASD subjects include a significant decrease at the phylum level in Cyanobacteria (0.015% vs. 0.074%, p < 0.0003), and a significant decrease at the genus level in Bacteroides (28.3% vs. 36.8%, p < 0.03). Species-level analysis showed a significant decrease in Faecalibacterium prausnitzii, Prevotella copri, Bacteroides fragilis, and Akkermansia municiphila. Mycobiome analysis showed an increase in the fungal Ascomycota phylum (98.3% vs. 94%, p < 0.047) and an increase in Candida albicans (27.1% vs. 13.2%, p < 0.055). Multivariate analysis showed that organisms from the genus Delftia were predictive of an increased odds ratio of ASD, whereas decreases at the phylum level in Cyanobacteria and at the genus level in Azospirillum were associated with an increased odds ratio of ASD. We screened 24 probiotic organisms to identify strains that could alter the growth patterns of organisms identified as elevated within ASD subject samples. In a preliminary in vivo preclinical test, we challenged wild-type Balb/c mice with Delftia acidovorans (increased in ASD subjects) by oral gavage and compared changes in behavioral patterns to sham-treated controls. An in vitro biofilm assay was used to determine the ability of potentially beneficial microorganisms to alter the biofilm-forming patterns of Delftia acidovorans, as well as their ability to break down fiber. Downregulation of cyanobacteria (generally beneficial for inflammation and wound healing) combined with an increase in biofilm-forming species such as D. acidovorans suggests that ASD-related GI symptoms may result from decreases in beneficial organisms with a concomitant increase in potential pathogens, and that beneficial probiotics can be identified that counteract these changes.

Oral lichen planus (OLP) is a common oral mucosal disease, clinically categorized into erosive OLP (EOLP) and non-erosive OLP (NEOLP) based on symptoms, but its pathogenic mechanism remains unclear. This study aims to explore the relationship between OLP and the oral microbiome.

We collected oral mucosal samples from 49 patients and 10 healthy individuals and conducted 16S rRNA and ITS gene sequencing to explore the oral fungal and bacterial communities.

We observed significantly lower α diversity of fungi in the EOLP group, with Candida being significantly enriched as the main dominant genus. In the NEOLP group, Aspergillaceae were significantly enriched. The EOLP group showed significant enrichment of Aggregatibacter and Lactobacillus, but the relative abundance of Streptococcus was notably lower than in the other two groups. In the NEOLP group, two species including Prevotella intermedia were significantly enriched. The microbial co-occurrence and co-exclusion networks display distinct characteristics across the three groups, with Lactobacillus assuming a significant bridging role in the ELOP group.

Our study indicates that EOLP and NEOLP experience varying degrees of dysbiosis at both the fungal and bacterial levels. Therefore, the pathogenic mechanisms and interactive relationships of these microbiota associated with OLP merit further in-depth investigation.

There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly studied.

A total of 111 individuals were prospectively enrolled: 89 IBD patients (52 ulcerative colitis and 37 Crohn's disease [CD]) and 22 healthy individuals. Disease characteristics were collected and a fecal calprotectin >100 μg/mg was considered indicative of activity. A subset of patients was followed for 6 ± 2 years. Disease course was designated as either complicated or uncomplicated based on the need of intensified medication and/or surgery. ITS sequencing was performed targeting the ITS1 region.

We found lower Ascomycota/Basidiomycota ratio in IBD. Patients showed a marked increase in Candida dublinensis and Ca albicans and were depleted of Aspergillus rubrobrunneus and Penicillium brevicompactum (P ≤ .001) Saccharomyces was predominant in total colitis and Penicillium in proctitis. Several Penicillium species were depleted in total colitis vs proctitis. Ileal CD patients were enriched in Debaromyces hansenii and depleted of Ca tropicalis (P ≤ .001). Ca albicans was overrepresented in inflammatory (B1) vs fibrostenosing (B2) CD. Ca dublinensis was more abundant in active patients and correlated positively with fecal calprotectin and neutrophil gelatinase-associated lipocalin, while S pastorianus correlated inversely with activity. Ca sake was associated with complicated disease and increased abundance of Cryptococcus carnescens with the need for surgery in CD.

This study shows important differences in the mycobiome in IBD and within phenotypes. Selected fungal species were associated with complicated disease and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD, with potential clinical implications.

Bile acids are steroids formed at the interface of host metabolism and intestinal microbiota. While primary bile acids are generated in the liver from cholesterol metabolism, secondary bile acids represent the products of microbial enzymes. Close to 100 different enzymatic modifications of bile acids structures occur in the human intestine and clinically guided metagenomic and metabolomic analyses have led to the identification of an extraordinary number of novel metabolites. These chemical mediators make an essential contribution to the composition and function of the postbiota, participating to the bidirectional communications of the intestinal microbiota with the host and contributing to the architecture of intestinal-liver and -brain and -endocrine axes. Bile acids exert their function by binding to a group of cell membrane and nuclear receptors collectively known as bile acid-regulated receptors (BARRs), expressed in monocytes, tissue-resident macrophages, CD4+ T effector cells, including Th17, T regulatory cells, dendritic cells and type 3 of intestinal lymphoid cells and NKT cells, highlighting their role in immune regulation. In this review we report on how bile acids and their metabolitesmodulate the immune system in inflammations and cancers and could be exploiting for developing novel therapeutic approaches in these disorders.

The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome.

Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

Recent advances in understanding how the microbiome can influence both the physiology and the pathogenesis of disease in humans have highlighted the importance of gaining a deeper insight into the complexities of the host-microbial dialogue. In tandem with this progress, has been a greater understanding of the biological pathways which regulate both homeostasis and inflammation at barrier tissue sites, such as the skin and the gut. In this regard, the Interleukin-1 family of cytokines, which can be segregated into IL-1, IL-18 and IL-36 subfamilies, have emerged as important custodians of barrier health and immunity. With established roles as orchestrators of various inflammatory diseases in both the skin and intestine, it is now becoming clear that IL-1 family cytokine activity is not only directly influenced by external microbes, but can also play important roles in shaping the composition of the microbiome at barrier sites. This review explores the current knowledge surrounding the evidence that places these cytokines as key mediators at the interface between the microbiome and human health and disease at the skin and intestinal barrier tissues.

The fungal component of the microbiota, the mycobiota, has been neglected for a long time due to its poor richness compared to bacteria. Limitations in fungal detection and taxonomic identification arise from using metagenomic approaches, often borrowed from bacteriome analyses. However, the relatively recent discoveries of the ability of fungi to modulate the host immune response and their involvement in human diseases have made mycobiota a fundamental component of the microbial communities inhabiting the human host, deserving some consideration in host-microbe interaction studies and in metagenomics. Here, we reviewed recent data on the identification of yeasts of the Ascomycota phylum across human body districts, focusing on the most representative genera, that is, Saccharomyces and Candida. Then, we explored the key factors involved in shaping the human mycobiota across the lifespan, ranging from host genetics to environment, diet, and lifestyle habits. Finally, we discussed the strengths and weaknesses of culture-dependent and independent methods for mycobiota characterization. Overall, there is still room for some improvements, especially regarding fungal-specific methodological approaches and bioinformatics challenges, which are still critical steps in mycobiota analysis, and to advance our knowledge on the role of the gut mycobiota in human health and disease. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Environmental Factors Infectious Diseases > Environmental Factors.

Inflammatory bowel disease is a chronic condition with a significant economic and social burden. The disease is complex and challenging to treat because it involves several pathologies, such as inflammation, oxidative stress, dysbiosis, and intestinal damage. The search for an effective treatment has identified cruciferous vegetables and their phytochemicals as potential management options for inflammatory bowel disease because they contain prebiotics, probiotics, and anti-inflammatory and antioxidant metabolites essential for a healthy gut. This critical narrative style review provides a robust insight into the pharmacological effects and benefits of crucifers and their documented bioactive compounds in in vitro and in vivo models, as well as clinical inflammatory bowel disease. The review highlights the significant impact of crucifer preparation and the presence of glucosinolates, isothiocyanates, flavonoids, and polyphenolic compounds, which are essential for the anti-inflammatory and antioxidative benefits of cruciferous vegetables, as well as their ability to promote the healthy microbial community and maintain the intestinal barrier. This review may serve as a viable nutritional guide for future research on methods and features essential to developing experiments, preventions, and treatments for inflammatory bowel disease. There is limited clinical information and future research may utilize current innovative tools, such as metabolomics, for adequate knowledge and effective translation into clinical therapy.

Multiple sclerosis (MS) arises from a complex interplay between host genetic factors and environmental components, with the gut microbiota emerging as a key area of investigation. In the current study, we used ion torrent sequencing to delve into the bacteriome (bacterial microbiota) and mycobiome (fungal microbiota) of people with MS (pwMS), and compared them to healthy controls (HC). Through principal coordinate, diversity, and abundance analyses, as well as clustering and cross-kingdom microbial correlation assessments, we uncovered significant differences in the microbial profiles between pwMS and HC. Elevated levels of the fungus Torulaspora and the bacterial family Enterobacteriaceae were observed in pwMS, whereas beneficial bacterial taxa, such as Prevotelladaceae and Dialister, were reduced. Notably, clustering analysis revealed overlapping patterns in the bacteriome and mycobiome data for 74% of the participants, with weakened cross-kingdom interactions evident in the altered microbiota of pwMS. Our findings highlight the dysbiosis of both bacterial and fungal microbiota in MS, characterized by shifts in biodiversity and composition. Furthermore, the distinct disease-associated pattern of fungi-bacteria interactions suggests that fungi, in addition to bacteria, contribute to the pathogenesis of MS. Overall, our study sheds light on the intricate microbial dynamics underlying MS, paving the way for further investigation into the potential therapeutic targeting of the gut microbiota in MS management.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity of the fungus to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of a C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. The colitis severity was evaluated using histology and a colonoscopy. The mice were mono-inoculated with C. albicans or C. tropicalis or co-challenged with both species. The mice were administered 3% DSS to induce acute colitis. The biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) and dry-weight assays. The abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. The co-challenged mice showed a decreased colitis severity compared to the mono-inoculated mice. The dry-weight assay demonstrated a marked decrease in C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface, leading to a reduction in biofilm formation.

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer, with a high mortality rate. There is growing evidence supporting a link between oral cancer and the microbiome. The microbiome can impact various aspects of cancer, such as pathogenesis, diagnosis, treatment, and prognosis. While there is existing information on bacteria and its connection to oral cancer, the fungi residing in the oral cavity represent a significant component of the microbiome that remains in its early stages of exploration and understanding. Fungi comprise a minuscule part of the human microbiome called the mycobiome. Mycobiome is ubiquitous in the human body but a weakened immune system offers a leeway space for fungi to showcase its virulence. The role of mycobiome as a colonizer, facilitator, or driver of carcinogenesis is still ambiguous. Reactivating the mycobiome that undergoes collateral damage associated with cancer treatment can be watershed event in cancer research. The coordinated, virulent, non-virulent behavior of the fungi once they reach a critical density must be hacked, considering its diagnostic, prognostic and therapeutic implications in cancer. This review highlights the diversity of the mycobiome and its potential role in oral cancer.

Reduced butyrate-production capacity has been reported in fecal microbial communities in patients with active ulcerative colitis. However, the butyrate-production capacity of the mucosal microbiome from active vs quiescent mucosa in ulcerative colitis has been unexplored. We sought to determine the diversity and relative abundance of mucosal bacterial and fungal communities from endoscopically active vs quiescent mucosa in patients with UC, and aimed to predict contributions of mucosal microbial communities to butyrate synthesis. Systematic, segmental right- and left-sided biopsies were obtained from endoscopically active (n = 13) or quiescent (n = 17) colonic mucosa, among 15 patients with pan-colonic ulcerative colitis. Dietary fiber intake of patients was performed using the validated five-item FiberScreen questionnaire. Amplicon sequencing of mucosal bacteria and fungi was performed. The diversity and relative abundance of mucosal bacterial and fungal taxa were quantified, and predicted contributions to butyrate synthesis were ascertained. Bacterial alpha and beta diversity were similar between active vs quiescent mucosa. Butyrogenic taxa were significantly increased in quiescence, including Butyricimonas, Subdoligranulum, and Alistipes. Predicted butyrate kinase activity was significantly and concomitantly increased in quiescent mucosa. Fiber intake was positively correlated with butyrogenic microbes. Compared to mucosal bacterial prevalence, mucosal fungi were detected in low prevalence. Butyrogenic microbes are relatively increased in quiescent mucosa in ulcerative colitis, and may be related to increased fiber intake during quiescence. Manipulation of the mucosal microbiome towards butyrate-producing bacteria may be associated with endoscopic quiescence.

Inflammatory bowel diseases (IBD) are chronic inflammatory gut disorders, majorly classified as ulcerative colitis and Crohn's disease. The complex, multifactorial etiopathogenesis of IBD involves genetic predisposition, environmental cues, aberrant mucosal immune response and a disturbed gut microbiota. Epidemiological trends, studies in gnotobiotic mice models and genome-wide association studies, identifying genes involved in microbial handling, together mount evidence in support of the gut microbiota playing a pivotal role in IBD pathogenesis. Both Crohn's disease and ulcerative colitis are characterized by severe dysbiosis of the gut microbiome, marked by an expansion of detrimental taxa and concomitant depletion of beneficial members. IBD is characterized by reduction in abundances of bacterial genera involved in production of short-chain fatty acids, bio-transformations of bile acids and synthesis of indole-based tryptophan compounds such as Faecalibacterium, Ruminococcus, Coprococcus, Dorea, Parabacteroides, Eubacterium, Oscillibacter and Prevotella and elevation in members of phyla Proteobacteria and Actinobacteria. This imbalance not only results in exaggerated immune signaling towards the microbial antigens, but also results in an altered metabolomic milieu that triggers additional inflammatory cascades. The present review provides insights into the bacterial dysbiosis observed across different intestinal sites and their metabolomic imprints participating in IBD.

Anti-Saccharomyces cerevisiae antibodies (ASCA) are human antibodies that can be detected using an enzyme-linked immunosorbent assay involving a mannose polymer (mannan) extracted from the cell wall of the yeast S. cerevisiae. The ASCA test was developed in 1993 with the aim of differentiating the serological response in two forms of inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis. The test, which is based on the detection of anti-oligomannosidic antibodies, has been extensively performed worldwide and there have been hundreds of publications on ASCA. The earlier studies concerned the initial diagnostic indications of ASCA and investigations then extended to many human diseases, generally in association with studies on intestinal microorganisms and the interaction of the micro-mycobiome with the immune system. The more information accumulates, the more the mystery of the meaning of ASCA deepens. Many fundamental questions remain unanswered. These questions concern the heterogeneity of ASCA, the mechanisms of their generation and persistence, the existence of self-antigens, and the relationship between ASCA and inflammation and autoimmunity. This review aims to discuss the gray areas concerning the origin of ASCA from an analysis of the literature. Structured around glycobiology and the mannosylated antigens of S. cerevisiae and Candida albicans, this review will address these questions and will try to clarify some lines of thought. The importance of the questions relating to the pathophysiological significance of ASCA goes far beyond IBD, even though these diseases remain the preferred models for their understanding.

Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.

Sepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied.

We assess persistence of the gut mycobiome perturbation (dysbiosis) in patients experiencing CCI following sepsis or trauma for up to two-to-three weeks after intensive care unit hospitalization.

We show that the dysbiotic mycobiome arrays shift toward a pathobiome state, which is more susceptible to infection, in CCI patients compared to age-matched healthy subjects. The fungal community in CCI patients is largely dominated by Candida spp; while, the commensal fungal species are depleted. Additionally, these myco-pathobiome arrays correlate with alterations in micro-ecological niche involving specific gut bacteria and gut-blood metabolites.

The findings reveal the persistence of mycobiome dysbiosis in both sepsis and trauma settings, even up to two weeks post-sepsis and trauma, highlighting the need to assess and address the increased risk of fungal infections in CCI patients.

Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.

Candida tropicalis-a prevalent gut commensal fungus in healthy individuals - contributes to intestinal health and disease. However, how commensal C. tropicalis influences intestinal homeostasis and barrier function is poorly understood. Here, we demonstrated that the reference strain of C. tropicalis (MYA-3404) ameliorated intestinal inflammation in murine models of chemically induced colitis and bacterial infection. Intestinal colonization of C. tropicalis robustly upregulated the expression of IL-17A and IL-22 to increase barrier function and promote proliferation of intestinal epithelial cells in the mouse colon. Metabolomics analysis of fecal samples from mice colonized with C. tropicalis revealed alterations in vitamin B3 metabolism, promoting conversion of nicotinamide to nicotinic acid. Although nicotinamide worsened colitis, treatment with nicotinic acid alleviated disease symptoms and enhanced epithelial proliferation and Th17 cell differentiation. Oral gavage of C. tropicalis mitigated nicotinamide-induced intestinal dysfunction in experimental colitis. Blockade of nicotinic acid production with nicotinamidase inhibitors lowered the protective effects against colitis in mice treated with C. tropicalis. Notably, a clinical C. tropicalis strain isolated from patients with candidemia lacked the protective effects against murine colitis observed with the reference strain. Together, our results highlight a novel role for C. tropicalis in resolving intestinal inflammation through the modulation of vitamin B3 metabolism.

Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.

The current studies have shown that the occurrence and development of chronic obstructive pulmonary disease (COPD) are closely related to the changes in gut health and its microenvironment, and even some gut diseases have significant clinical correlation with COPD. The dysbiosis of gut microbiota observed in COPD patients also suggests a potential bidirectional interaction between the gut and lung. Communication between the gut and lung may occur through circulating inflammatory cells, gut microbial metabolites, and circulating inflammatory mediators, but the mechanism of bidirectional communication between the gut and lung in COPD is still under study. Therefore, more research is still needed in this area. In this review, we summarize recent clinical studies and animal models on the role of the gut-lung axis in the occurrence and development of COPD and its mechanisms, so as to provide ideas for further research in this field. In addition, we also summarized the negative effects of COPD medication on gut microbiota and the gut microbiota risk factors for COPD and proposed the potential prevention and treatment strategies.

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.