Gut bacterial and fungal dysbiosis in tuberculosis patients.

BACKGROUND: Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. RESULTS: The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. CONCLUSIONS: Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

BACKGROUND AND PURPOSE: Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. METHODS: Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. RESULTS: The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC] = 0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC = 0.85, 95% CI = 0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. CONCLUSIONS: Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

Draft Genome Sequence of a Primate Isolate of Kazachstania pintolopesii.

Kazachstania pintolopesii is an opportunistic mammalian pathobiont from the K. telluris species complex. No draft genomes of this species are currently available. Here, we report the first draft genome sequence of a primate isolate of K. pintolopesii (NCYC 4417).

A Comparison of Methods of Gut Microbiota Transplantation for Preclinical Studies.

The experimental details reported in preclinical fecal microbiota transplantation (FMT) protocols are highly inconsistent, variable, and/or incomplete. We therefore evaluated FMT from a human donor to antibiotic-induced microbial-depleted mice by exploring the effects of six techniques based on antibiotic (AB) or antibiotic + antimycotic (AB + T) gut decontamination, different administration routes, and different dosing intervals on the gut microbial population, assessed using 16S and 18S sequencing. In addition, we explored the effectiveness of FMT in terms of inflammation, physiological, and behavioral outcomes. Our results showed that intrarectal FMT at low dosing intervals better preserved the donor's gut bacterial community at genus level. Furthermore, we showed a lower abundance of several genera of fungi in animals treated with AB + T. In addition, we observed that AB + T gut decontamination followed by per os FMT, once every 3 days, affected behavioral parameters when compared to other FMT techniques. Accordingly, the same FMT groups that showed an association with some of the behavioral tests were also related to specific gut fungal genera, suggesting a possible mediation. Our findings may be useful for optimizing the practice of FMT and also in terms of donor microbiota preservation. This information may help to improve the reproducibility and reliability of FMT studies.

Gut microbiota profiles and characterization of cultivable fungal isolates in IBS patients.

Studies so far conducted on irritable bowel syndrome (IBS) have been focused mainly on the role of gut bacterial dysbiosis in modulating the intestinal permeability, inflammation, and motility, with consequences on the quality of life. Limited evidences showed a potential involvement of gut fungal communities. Here, the gut bacterial and fungal microbiota of a cohort of IBS patients have been characterized and compared with that of healthy subjects (HS). The IBS microbial community structure differed significantly compared to HS. In particular, we observed an enrichment of bacterial taxa involved in gut inflammation, such as Enterobacteriaceae, Streptococcus, Fusobacteria, Gemella, and Rothia, as well as depletion of health-promoting bacterial genera, such as Roseburia and Faecalibacterium. Gut microbial profiles in IBS patients differed also in accordance with constipation. Sequence analysis of the gut mycobiota showed enrichment of Saccharomycetes in IBS. Culturomics analysis of fungal isolates from feces showed enrichment of Candida spp. displaying from IBS a clonal expansion and a distinct genotypic profiles and different phenotypical features when compared to HS of Candida albicans isolates. Alongside the well-characterized gut bacterial dysbiosis in IBS, this study shed light on a yet poorly explored fungal component of the intestinal ecosystem, the gut mycobiota. Our results showed a differential fungal community in IBS compared to HS, suggesting potential for new insights on the involvement of the gut mycobiota in IBS. KEY POINTS: • Comparison of gut microbiota and mycobiota between IBS and healthy subjects • Investigation of cultivable fungi in IBS and healthy subjects • Candida albicans isolates result more virulent in IBS subjects compared to healthy subjects.

Modern perspectives on the health benefits of kefir in next generation sequencing era: Improvement of the host gut microbiota.

Kefir is a natural complex fermented milk product containing more than 50 species of probiotic bacteria and yeast, and has been demonstrated to have multiple properties conferring health benefits, including antiobesity, anti-hepatic steatosis, antioxidative, antiallergenic, antitumor, anti-inflammatory, cholesterol-lowering, constipation-alleviating, and antimicrobial properties. To better understand the underlying mechanisms of these benefits, we here review research on the effect of kefir (and kefir microorganisms) consumption to modulate the host gut microbiota. Owing to its excellent gastrointestinal resistance and colonization ability and wide ranges of microbial interaction, kefir has shown significant and wide-spectrum modulatory effects on the host gut microbiota. In particular, as a bacteria- and yeast-containing food, kefir can modulate both the gut microbiota and mycobiota. Since the association of this modulation with health benefit has only been addressed in a small number of recent studies thus far, further studies are needed to determine the precise mechanisms of the beneficial effects of kefir in relation to the modulation of the gut microbiota and mycobiota. Gaining this insight will surely help to take full advantage of this unique probiotic food.

Into the era of mycobiome-driven cancer research.

The cancer mycobiome has recently become a research hotspot. While the intratumor mycobiota is implicated in cancer initiation and progression, the gut mycobiota functions as biomarkers for cancer diagnosis and treatment. In this forum article we highlight the involvement of the mycobiome in correlation-, causation-, and prediction-oriented cancer research and discuss the potential of this burgeoning field.

Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis. METHODS: By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs). RESULTS: Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients. CONCLUSIONS: We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.

In this study, we report the gut microbiota and mycobiota dysbiosis in pediatric patients affected by primary sclerosing cholangitis (PSC) associated with ulcerative colitis (UC), with an increase in pro-inflammatory pathobionts and a reduction in anti-inflammatory commensals.

Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

Associations between bacterial and fungal communities in the human gut microbiota and their implications for nutritional status and body weight.

This study examined the interplay between bacterial and fungal communities in the human gut microbiota, impacting on nutritional status and body weight. Cohorts of 10 participants of healthy weight, 10 overweight, and 10 obese individuals, underwent comprehensive analysis, including dietary, anthropometric, and biochemical evaluations. Microbial composition was studied via gene sequencing of 16S and ITS rDNA regions, revealing bacterial (bacteriota) and fungal (mycobiota) profiles. Bacterial diversity exceeded fungal diversity. Statistically significant differences in bacterial communities were found within healthy-weight, overweight, and obese groups. The Bacillota/Bacteroidota ratio (previously known as the Firmicutes/Bacteroidetes ratio) correlated positively with body mass index. The predominant fungal phyla were Ascomycota and Basidiomycota, with the genera Nakaseomyces, Kazachstania, Kluyveromyces, and Hanseniaspora, inversely correlating with weight gain; while Saccharomyces, Debaryomyces, and Pichia correlated positively with body mass index. Overweight and obese individuals who harbored a higher abundance of Akkermansia muciniphila, demonstrated a favorable lipid and glucose profiles in contrast to those with lower abundance. The overweight group had elevated Candida, positively linked to simple carbohydrate consumption. The study underscores the role of microbial taxa in body mass index and metabolic health. An imbalanced gut bacteriota/mycobiota may contribute to obesity/metabolic disorders, highlighting the significance of investigating both communities.

Description of Gut Mycobiota Composition and Diversity of Caprinae Animals.

The fungal community, also known as mycobiota, plays pivotal roles in host nutrition and metabolism and has potential to cause disease. However, knowledge of the gut fungal structure in Caprinae is quite limited. In this study, the composition and diversity of the gut mycobiota of Caprinae animals from different geographical locations (Anhui, Jilin, Guangxi, Shandong, Shanxi, and Tibet) were comprehensively characterized by analyzing the internal transcribed spacer 2 (ITS-2) sequences of the fungal community. The results showed that Ascomycota and Basidiomycota were the dominant phyla, which, respectively, accounted for 90.86 to 95.27% and 2.58 to 7.62% of sequences in samples from each region. Nonetheless, the structure of the gut mycobiota was largely different in Caprinae animals in the different provinces. Therein, Sporormiaceae and Thelebolaceae were the dominant fungal families in the samples from Tibet, whereas their abundance was generally low in other regions. The intestinal diversity of individuals from Guangxi was higher than that in other regions. In addition, there were 114 differential genera among all regions. Finally, the co-occurrence network revealed 285 significant correlations in cross-family pairs in the guts of Caprinae animals, which contained 149 positive and 136 negative relationships, with 96 bacterial and 86 fungal participants at the family level. This study has improved the understanding of the mycobiota of ruminants and provided support for the improvement in animal health and productivity. IMPORTANCE In this study, we elucidated and analyzed the structure of the gut mycobiota of Caprinae animals from different regions. This study revealed differences in the structure of the gut mycobiota among Caprinae animals from different geographical environments. Based on previous findings, correlations between fungal and bacterial communities were analyzed. This study adds to previous research that has expanded the present understanding of the gut microbiome of Caprinae animals.

Longitudinal gut mycobiota changes in Japanese infants during first three years of life.

Although fungi can have a large impact on host health through the stimulation of the immune system and toxin production, few studies have investigated the gut mycobiota during infancy, a period during which sensitivity to internal and external stimuli is high. To capture the trend in fungal colonization during infancy, we evaluated the gut mycobiota of ten Japanese infants during the first 3 years of life. Infants had two major phyla, Ascomycota (68.9%) and Basidiomycota (29.6%), and the most abundant genus was Saccharomyces (26.8%), followed by Malassezia (18.5%), Candida (12.3%), Meyerozyma (8.5%), and Penicillium (8.3%). Alpha diversity analysis revealed a significant decrease in fungal richness and evenness with age, suggesting adaptive selection of the colonizing species in the gut environment. Beta diversity analysis divided infant mycobiota into age-related clusters and showed discrete separation before and after weaning, suggesting shift in microenvironment via weaning. In the initial stage, a variety of fungal species that likely originated from an environment, such as Malassezia spp., was highly colonized and were replaced by yeasts, such as Saccharomyces, after weaning. Further studies are needed to shed light on how the passage of the series of fungal colonizations in infancy affects the development of the host immune system and the other homeostasis involved in health later in life.

Alteration in gut mycobiota of patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a serious disease characterized by high androgen, insulin resistance (IR), hyperglycemia, and obesity, leading to infertility. The gut mycobiota has been reported to evolve in metabolic diseases including obesity, hyperglycemia, and fatty liver. However, little is known about the gut mycobiota and PCOS. In the current study, we recruited 17 PCOS patients and 17 age-matched healthy controls for community structure and functional analysis of the gut mycobiota. The results showed that PCOS patients have reduced diversity and richness of the gut microbiota compared with healthy controls. ß-Diversity analysis showed that the community structure of the gut microbiota of patients with PCOS was significantly different from healthy controls. At the phylum level, PCOS patients have reduced Basidiomycota and increased Ascomycota compared with healthy controls. At the family level, the higher relative abundance of Saccharomycetaceae and lower Trichosporonaceae and Ascomycota_unclassified were detected in PCOS patients than in healthy controls. At the genus level, different microbial compositions were also observed between PCOS patients and healthy controls. In addition, PICRUSt2 showed that patients with PCOS have different microbial functions in the gut compared with healthy controls. LEfSe indicated that Saccharomyces and Lentinula were enriched in the fecal samples of PCOS patients, while Aspergillus was depleted compared with healthy controls. Our finding indicates that PCOS patients have different community structures and functions of the gut mycobiota, which provides new insight into PCOS pathogenesis and intervention. IMPORTANCE It was found that intestinal fungi as well as serum metabolites in PCOS patients were significantly different from those in healthy subjects. However, no studies have been done to show exactly which fungus interacts with which bacteria in humans or which fungus acts alone. As fungal research progresses, it will be possible to fill this gap.

Intestinal microbiome dysbiosis in alcohol-dependent patients and its effect on rat behaviors.

IMPORTANCE: Intestinal microbiome dysbiosis is associated with psychiatric disease through the "microbiota-gut-brain" axis. Here, we revealed that there was obvious intestinal microbiome (including bacterial and fungal) dysbiosis in alcohol-dependent patients. Alcohol consumption seriously disturbs the gut equilibrium between bacteria and fungi, reduces the interactions among bacterial-fungal trans-kingdom, and increases intestinal permeability. Gut microbiota should be considered as a whole to study the development of alcohol dependence. The gut microbiome of alcohol-dependent patients increased the anxiety- and depression-like behavior in rats. The gut microbiota dysbiosis may promote the development of alcohol dependence by regulating the endogenous cholecystokinin (CCK) and related receptors. Hence, regulating the balance of gut microbiota and the endogenous CCK may be a potential strategy for reducing the risk of relapse in alcohol addiction patients.

A Clinical Study Provides the First Direct Evidence That Interindividual Variations in Fecal ß-Lactamase Activity Affect the Gut Mycobiota Dynamics in Response to ß-Lactam Antibiotics.

Antibiotics disturb the intestinal bacterial microbiota, leading to gut dysbiosis and an increased risk for the overgrowth of opportunistic pathogens. It is not fully understood to what extent antibiotics affect the fungal fraction of the intestinal microbiota, the mycobiota. There is no report of the direct role of antibiotics in the overgrowth in healthy humans of the opportunistic pathogenic yeast Candida albicans. Here, we have explored the gut mycobiota of 22 healthy subjects before, during, and up to 6 months after a 3-day regimen of third-generation cephalosporins (3GCs). Using ITS1-targeted metagenomics, we highlighted the strong intra- and interindividual diversity of the healthy gut mycobiota. With a specific quantitative approach, we showed that C. albicans prevalence was much higher than previously reported, with all subjects but one being carriers of C. albicans, although with highly variable burdens. 3GCs significantly altered the mycobiota composition and the fungal load was increased both at short and long term. Both C. albicans relative and absolute abundances were increased but 3GCs did not reduce intersubject variability. Variations in C. albicans burden in response to 3GC treatment could be partly explained by changes in the levels of endogenous fecal ß-lactamase activity, with subjects characterized by a high increase of ß-lactamase activity displaying a lower increase of C. albicans levels. A same antibiotic treatment might thus affect differentially the gut mycobiota and C. albicans carriage, depending on the treated subject, suggesting a need to adjust the current risk factors for C. albicans overgrowth after a ß-lactam treatment. IMPORTANCE Fungal infections are redoubtable healthcare-associated complications in immunocompromised patients. Particularly, the commensal intestinal yeast Candida albicans causes invasive infections in intensive care patients and is, therefore, associated with high mortality. These infections are preceded by an intestinal expansion of C. albicans before its translocation into the bloodstream. Antibiotics are a well-known risk factor for C. albicans overgrowth but the impact of antibiotic-induced dysbiosis on the human gut mycobiota-the fungal microbiota-and the understanding of the mechanisms involved in C. albicans overgrowth in humans are very limited. Our study shows that antibiotics increase the fungal proportion in the gut and disturb the fungal composition, especially C. albicans, in a subject-dependent manner. Indeed, variations across subjects in C. albicans burden in response to ß-lactam treatment could be partly explained by changes in the levels of endogenous fecal ß-lactamase activity. This highlighted a potential new key factor for C. albicans overgrowth. Thus, the significance of our research is in providing a better understanding of the factors behind C. albicans intestinal overgrowth, which might lead to new means to prevent life-threatening secondary infections.

Analysis of Intestinal Mycobiota of Patients with Clostridioides difficile Infection among a Prospective Inpatient Cohort.

Clostridioides difficile infection (CDI) is a burden to health care systems worldwide. Gut microbiota dysbiosis associated with CDI has been well accepted. However, contribution of fungal mycobiota to CDI has recently gained research interest. Here, we report the gut mycobiota composition of 149 uniquely well characterized participants from a prospective clinical cohort and evaluate the discriminating ability of gut mycobiota to classify CDI and non-CDI patients. Fecal samples were divided into two groups: (i) CDI (inpatients who had clinically significant diarrhea and positive nucleic acid amplification testing [NAAT] and received subsequent CDI therapy, n = 58) and (ii) non-CDI, which can be further divided into three subgroups: (a) carrier (inpatients with positive stool NAAT but without diarrhea; n = 28); (b) diarrhea (inpatients with negative stool NAAT; n = 31); and (c) control (inpatients with negative stool NAAT and without diarrhea; n = 32). Fecal mycobiota composition was analyzed by internal transcribed spacer 2 (ITS2) sequencing. In comparison to non-CDI patients, CDI patients tend to have gut mycobiota with lower biodiversity, weaker fungi correlations, and weaker correlations between fungi and host immune factors. Notably, 11 genera (Saccharomyces, Penicillium, Aspergillus, Cystobasidium, Cladosporium, and so on) were significantly enriched in non-CDI patients, and Pichia and Suhomyces were enriched in patients with CDI, while 1 two genera, Cystobasidium and Exophiala, had higher abundance in patients with diarrhea compared with CDI (linear discriminant analysis [LDA] > 3.0; P < 0.05). Ascomycota and Basidiomycota (or Candida and Saccharomyces) exhibited a strong negative correlation (r ≤ -0.714 or r ≤ -0.387; P < 0.05), and the ratios of Ascomycota to Basidiomycota or genera Candida to Saccharomyces were dramatically higher in CDI patients than in non-CDI patients (P < 0.05). A disease-specific pattern with much weaker fungal abundance correlations was observed in the CDI group compared to that in the non-CDI and diarrhea groups, suggesting that these correlations may contribute to the development of CDI. Our findings provided specific markers of stool fungi that distinguish CDI from all non-CDI hospitalized patients. This study's potential clinical utility for better CDI diagnosis warrants further investigation. IMPORTANCE Clostridioides difficile is an opportunistic bacterial pathogen that causes a serious and potentially life-threatening infection of the human gut. It remains an existing challenge to distinguish active infection of CDI from diarrhea with non-CDI causes. A few large prospective studies from recent years suggest that there is no single optimal test for the diagnosis of CDI. Previous research has concentrated on the relationship between bacteria and CDI, while the roles of fungi, as a significant proportion of the gut microbial ecosystem, remain understudied. In this study, we report a series of fungal markers that may add diagnostic values for the development of a more systematic approach to accurate CDI diagnosis. These results help open the door for better understanding of the relationship between host immune factors and the fungal community in the context of CDI pathogenesis.

Alterations of gut fungal microbiota in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease, in addition, gut microbiota plays an important role in the etiology of RA. However, our understanding of alterations to the gut fungal microbiota in Chinese population with RA is still limited. METHODS: Serum samples were obtained from 62 patients with RA, and 39 age- and gender-matched healthy controls (HCs). Fecal samples were obtained from 42 RA patients and 39 HCs. Fecal fungal microbiota targeting internal transcribed spacer region 2 (ITS2) rRNA genes was investigated using MiSeq sequencing, as well as their associations with some diagnostic biomarkers for RA. RESULTS: Our results showed that the fungal diversity did not alter in RA patients but taxonomic composition of the fecal fungal microbiota did. The gut mycobiota of RA patients was characterized by decreased abundance of Pholiota, Scedosporium, and Trichosporon. The linear discriminant analysis (LDA) effect size analysis (LEfSe) analysis identified several RA-enriched fungal genera, which were positively correlated with most RA biomarkers. Furthermore, since RA is an age- and gende-related disease, we classified RA patients into subgroups with age and gender and analyzed the sequencing results. Our data demonstrated that Wallemia and Irpex were the most discriminatory against RA patients over 60 years old, while Pseudeurotiaceae was the most discriminatory against female RA patients. CONCLUSIONS: The case-control study presented here confirmed the alterations of gut fungal microbiota in Chinese patients with RA, and we speculated that the fungal dysbiosis may contribute to RA development.

Alterations of Gut Mycobiota Profiles in Adenoma and Colorectal Cancer.

Accumulating evidence indicates that gut microbiota dysbiosis contributes to colorectal cancer and adenoma. However, a few studies revealed the altered gut mycobiota architecture in colorectal cancer. The present study characterized the gut mycobiota profiles in adenoma and colorectal cancer patients by metagenomic sequencing. Malassezia restricta increased, while Leucoagaricus_sp_SymCcos and fungal_sp_ARF18 significantly decreased in adenoma. Phanerochaete_chrysosporium, Lachancea_waltii, and Aspergillus_rambellii were the top 3 fungi that were significantly enriched in colorectal cancer, while Candida_versatilis, Pseudocercospora_pini_densiflorae, and Candida_sp_JCM_15000 were dominant in the healthy controls. Thirteen fungi, ranked as critical biomarkers in diagnosing colorectal cancer, showed positive associations among all samples. Lachancea_waltii and Phanerochaete_chrysosporium showed the most significant association within CRC. The values of area under the receiver-operating characteristics curve (AUROC) of selected 13 mycobiota were 0.926 in the training model and 0.757 in the 10-fold validation model. Our study provided a reliable investigation of the alterations of gut mycobiota in the development of colorectal cancer and established a convincing diagnostic model for colorectal cancer, which might improve the treatment strategy for colorectal cancer in the future.

Mycobiota and C-Type Lectin Receptors in Cancers: Know thy Neighbors.

Numerous studies have demonstrated the importance of gut bacteria in the development of malignancy, while relatively little research has been done on gut mycobiota. As a part of the gut microbiome, the percentage of gut mycobiota is negligible compared to gut bacteria. However, the effect of gut fungi on human health and disease is significant. This review systematically summarizes the research progress on mycobiota, especially gut fungi, in patients with head and neck cancer (HNC), esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer, melanoma, breast cancer, and lung carcinoma-induced cachexia. Moreover, we also describe, for the first time in detail, the role of the fungal recognition receptors, C-type lectin receptors (CLRs) (Dectin-1, Dectin-2, Dectin-3, and Mincle) and their downstream effector caspase recruitment domain-containing protein 9 (CARD9), in tumors to provide a reference for further research on intestinal fungi in the diagnosis and treatment of malignant tumors.

Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test.

The aims of this observational "proof-of-concept" study were to analyze the clinical/psychological characteristics and gut microbiota/mycobiota composition of individuals with suspected non-celiac gluten/wheat sensitivity (NCGS/WS) according to responses to the double-blind-placebo-controlled (DBPC) crossover gluten challenge test. Fifty individuals with suspected NCGS/WS were subjected to the DBPC challenge test; anthropometric measurements, psychometric questionnaires, and fecal samples were collected. Twenty-seven (54%) participants were gluten responsive (NCGS), and 23 were placebo responsive, with an order effect. NCGS individuals displayed a significantly lower risk of eating disorders and a higher mental health score when compared to placebo-responsive participants, confirmed by multiple logistic regression analyses (OR = 0.87; 95% CI 0.76-0.98, p = 0.021, and OR = 1.30; 95% CI 1.06-1.59, p = 0.009, respectively). Principal coordinate analyses based on microbiota composition showed a separation by the DBPC response (p = 0.039). For Bacteroides (p = 0.05) and Parabacteroides (p = 0.007), the frequency of amplicon sequence variants was lower, and that for Blautia (p = 0.009) and Streptococcus (p = 0.004) was higher in NCGS individuals at multiple regression analyses. No difference in the mycobiota composition was detected between the groups. In conclusion, almost half of the individuals with suspected gluten sensitivity reported symptoms with placebo; they showed lower mental health scores, increased risk for eating disorders, and a different gut microbiota composition.