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Introduction: Despite advancements in the treatment of benign prostatic hyperplasia (BPH), the mechanisms underlying BPH development and progression remain elusive and lacks a one-size-fits-all therapeutic solution. Prostatic inflammation contributes to BPH and lower urinary tract symptoms (LUTS), but the initial trigger remains unknown. Current research suggests dysbiosis of the urinary microbiome as a potential culprit. This systematic review explores the emerging field of the male urinary and prostatic microbiome and its relationship with BPH/LUTS., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A systematic search in the Pubmed and Scopus databases was performed using specific terms. Inclusion criteria considered male non-neurogenic patients with LUTS due to BPH with analyses of urinary microbiome, concerning evaluation of English-language publications with relevance., Results: Among seven articles involving 542 patients, there was an association between male LUTS/BPH and the urinary microbiome. Findings indicate a correlation between urinary microbiome dysbiosis and LUTS severity, with specific bacterial genera such as Streptococcus and Haemophilus linked to higher International Prostate Symptom Score (IPSS) scores and PSA levels. The fecal microbiome may be associated with LUTS, although contradictory findings are reported. The review also highlights methodological inconsistencies, small sample sizes, few negative controls and a lack of comprehensive clinical data as major limitations., Conclusions: While there is an undeniable correlation between the microbiome and LUTS/BPH, future research should aim to standardize sampling techniques and expand the score to include functional microbiome characterization, potentially leading to novel, microbiome-targeted therapeutic strategies for BPH., (© 2024 Wiley Periodicals LLC.)

Fecal samples were collected from 640 individuals in Korea, including 523 patients with IBD (223 with Crohn's disease [CD] and 300 with ulcerative colitis [UC]) and 117 healthy controls. The samples were subjected to cross-sectional gut metagenomic analysis using 16 S rRNA sequencing and bioinformatics analysis. Patients with IBD, particularly those with CD, exhibited significantly lower alpha diversities than the healthy subjects. Differential abundance analysis revealed dysbiotic signatures, characterized by an expansion of the genus Escherichia-Shigella in patients with CD. Functional annotations showed that functional pathways related to bacterial pathogenesis and production of hydrogen sulfide (H 2 S) were strongly upregulated in patients with CD. A dysbiosis score, calculated based on functional characteristics, highly correlated with disease severity. Markers distinguishing between healthy subjects and patients with IBD showed accurate classification based on a small number of microbial taxa, which may be used to diagnose ambiguous cases. These findings confirm the taxonomic and functional dysbiosis of the gut microbiota in patients with IBD, especially those with CD. Taxa indicative of dysbiosis may have significant implications for future clinical research on the management and diagnosis of IBD., (© 2024. The Author(s).)

Recent interest in noninvasive diagnostic approaches has highlighted the potential of urinary microbiota as a novel biomarker for bladder cancer. This study investigated the urinary microbiota of 30 bladder cancer patients and 32 healthy controls using a specific NGS protocol that sequences eight hypervariable regions of the 16S rRNA gene, providing detailed insights into urinary microbiota composition. The relative abundance of microbial compositions in urine samples from cancer patients and healthy controls was analyzed across various taxonomic levels. No notable differences were highlighted at the phylum, class, order, and family levels. At the genus level, 53% of detected genera were represented in either cancer patients or healthy controls. Microbial diversity was significantly lower in cancer patients. The differential analysis identified five genera, Rhodanobacter , Cutibacterium , Alloscardovia , Moryella , and Anaeroglobus , that were significantly more abundant in cancer patients. Notably, Rhodanobacter was present in 20 cancer samples but absent in healthy controls. Conversely, 40 genera, including Lactobacillus, Propionibacterium , and Bifidobacterium , exhibited reduced abundance in cancer patients. These findings suggest that some genera may serve as potential biomarkers for bladder cancer, highlighting the need for further research to explore their roles in disease pathogenesis and their potential applications in diagnostics and therapeutics.

Type 2 diabetes mellitus (T2DM) is globally recognized as a significant health concern, with diabetic foot (DF) identified as a severe long-term complication that can lead to tissue death or amputation. The discovery of the impact of mycobiota, a diverse group of multicellular eukaryotes in the gut microbiome, on the onset of endocrine disorders holds great significance. Therefore, this research aimed to examine variations in fungal mycobiome and identify potential biomarkers for T2DM and T2DM-DF. Fecal and blood samples were collected from 33 individuals with T2DM, 32 individuals with T2DM-DF, and 32 healthy individuals without any health conditions (HC). Blood samples were used for laboratory parameters analysis, while total DNA was extracted from fecal samples and sequenced using Illumina 18s rRNA. Bioinformatics tools were employed to analyze fungal abundance and diversity, revealing differentially expressed fungal species and signature fungi that distinguished between T2DM, T2DM-DF, and HC groups. Firstly, significant alterations in some laboratory parameters were observed among the three groups, which also differed between T2DM and T2DM-DF. The diversity of gut fungi in T2DM and T2DM-DF significantly differed from that of the HC group; however, more pronounced changes were observed in T2DM-DF. Additionally, two significantly altered phyla, Ascomycota and Basidiomycota, were identified with higher Ascomycota abundance but lower Basidiomycota abundance in both the T2DM and T2DM-DF compared to the HC group. Furthermore, the top 15 fungi showing significant changes at the species level included a notable decrease in Rhodotorula_mucilaginosa abundance in patients with T2DM compared to HC and a substantial increase in unclassified_g_Candida abundance specifically seen only among patients with T2DM-DF, but not among those diagnosed with T2DM or HC. Thirdly, KEGG was employed to analyze enzyme expression across the three groups, revealing a more pronounced alteration in gut fungal function within T2DM-DF compared to T2DM. Subsequently, to accurately identify signature fungi in each group, a random forest was utilized to rank the top 15 significant fungi. Notably, 11 fungi were identified as potential biomarkers for distinguishing T2DM or T2DM-DF from HC, while eight fungi could discriminate between T2DM and T2DM-DF. Furthermore, receiver operating characteristic curve (ROC) analysis demonstrated enhanced accuracy of predicted outcomes. These findings suggest that changes in fungal mycobiome are closely associated with the progression and complications of T2DM and DF, offering promising prospects for diagnosis and treatment., (© 2024. The Author(s).)

Aim: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children., Methods: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D-DIA proteomics were performed., Results: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis., Conclusion: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders"., (© 2024 Asian Pacific Society of Nephrology.)

Objective: To identify the vaginal microbial signature in women with chronic endometritis (CE) and investigate the potential of vaginal microbiome characterization as a novel diagnostic tools for CE., Methods: A cross-sectional study was conducted to compare the characteristics of the vaginal microbiome in 98 women who underwent endometrial biopsy for routine clinical inspection of infertility (49 women diagnosed with CE and 49 with non-CE). The vaginal microbiome was analyzed using 16S ribosomal RNA gene amplicon sequencing. The study included an analysis of diversity, bacterial abundance, and microbial function. In addition, microbial markers were identified, and a CE classifier was developed., Results: The relative abundances of genera, including Bifidobacterium, Prevotella and Gardnerella, were found to be different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways reported differential expression in metabolism-related pathways in the two groups. We identified four microbial markers of CE (Enterobacter, Prevotella, Faecalibacterium, and Phascolarctobacterium) and developed a predictive classifier for diagnosing CE, achieving an area under the curve of 83.26%., Conclusion: The results of the current study revealed that, compared with the non-CE controls, patients with CE have a different vaginal microbiota, highlighting the diagnostic significance of the vaginal microbiome as a promising noninvasive biomarker in detecting CE., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: The gut-lung axis, pivotal for respiratory health, is inadequately explored in pulmonary and critical care medicine (PCCM) inpatients., Methods: Examining PCCM inpatients from three medical university-affiliated hospitals, we conducted 16S ribosomal RNA sequencing on stool samples (inpatients, n = 374; healthy controls, n = 105). We conducted statistical analyses to examine the gut microbiota composition in PCCM inpatients, comparing it to that of healthy controls. Additionally, we explored the associations between gut microbiota composition and various clinical factors, including age, white blood cell count, neutrophil count, platelet count, albumin level, hemoglobin level, length of hospital stay, and medical costs., Results: PCCM inpatients exhibited lower gut microbiota diversity than healthy controls. Principal Coordinates Analysis revealed marked overall microbiota structure differences. Four enterotypes, including the exclusive Enterococcaceae enterotype in inpatients, were identified. Although no distinctions were found at the phylum level, 15 bacterial families exhibited varying abundances. Specifically, the inpatient population from PCCM showed a significantly higher abundance of Enterococcaceae, Lactobacillaceae, Erysipelatoclostridiaceae, Clostridiaceae, and Tannerellaceae. Using random forest analyses, we calculated the areas under the receiver operating characteristic curves (AUCs) to be 0.75 (95% CIs 0.69-0.80) for distinguishing healthy individuals from inpatients. The four most abundant genera retained in the classifier were Blautia, Subdoligranulum, Enterococcus, and Klebsiella., Conclusions: Evidence of gut microbiota dysbiosis in PCCM inpatients underscores the gut-lung axis's significance, promising further avenues in respiratory health research., (© 2024. The Author(s).)

The gut microbiota has acquired significant attention in recent years for its potential as a diagnostic biomarker for colorectal cancer (CRC). In this literature review, we looked at the studies exploring alterations in gut microbiota composition associated with CRC, the potential mechanisms linking gut dysbiosis to CRC development, and the diagnostic approaches utilizing gut microbiota analysis. Our research has led to the conclusion that individuals with CRC often display alterations in their gut microbiota composition compared to healthy individuals. These alterations can include changes in the diversity, abundance, and type of bacteria present in the gut. While the use of gut microbiota as a diagnostic biomarker for CRC holds promise, further research is needed to validate its effectiveness and standardize testing protocols. Additionally, considerations such as variability in the microbiota composition among individuals and potential factors must be addressed before microbiota-based tests can be widely implemented in clinical practice.

The association between oral dysbiosis and celiac disease (CD) remains poorly understood, as does the impact of CD-associated dysbiosis on disease development or exacerbation. This study aims to investigate alterations in salivary microbial composition among children with CD. In this cross-sectional study, saliva samples from 12 children with active CD (A-CD group), 14 children with CD on a gluten-free diet (GFD), and 10 healthy control (HC) children were analyzed using DNA sequencing targeting the 16S ribosomal RNA. Both patients in A-CD and GFD groups showed a significant increase (p = 0.0001) in the Bacteroidetes phylum, while the Actinobacteria phylum showed a significant decrease (p = 0.0001). Notably, the Rothia genus and R.aeria also demonstrated a significant decrease (p = 0.0001) within the both CD groups as compare to HC. Additionally, the control group displayed a significant increase (p = 0.006) in R.mucilaginosa species compared to both CD patient groups. Distinct bacterial strains were abundant in the saliva of patients with active CD, indicating a unique composition of the salivary microbiome in individuals with CD. These findings suggest that our approach to assessing salivary microbiota changes may contribute to developing noninvasive methods for diagnosing and treating CD., (© 2024. The Author(s).)

Increased intestinal permeability and gut dysbiosis are important factors in the pathophysiology of psoriasis and its associated conditions. Claudin-3 is a protein that is found in tight junctions and may be used to assess the integrity of the gut barrier. The aim of this study was to investigate serum concentration of Claudin- 3 (CLDN3) in patients with psoriasis. Exploring its possible relations with patients' demographic, clinical and laboratory findings was another objective. Fifty psoriatic patients and thirty-five age- and sex-matched healthy volunteers served as the study's control group in this case-control, hospital-based research. The amount of serum CLDN3 was determined by means of an enzyme-linked immunosorbent test (ELISA). Concentration of serum CLDN3 was found to be significantly higher in patients with psoriasis. (p = 0.002). There was no statistically significant correlation between CLDN3 and patient's clinical & laboratory variables. We demonstrated that gut permeability is dysfunctional in patients with psoriasis as indicated by reduction of serum CLDN3. Further investigations are needed to determine whether modulation of gut barrier may represent a new therapeutic approach for psoriasis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 μg/g; n = 602), moderate (> 50-100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals., (© 2024. The Author(s).)

Purpose: Stomach and esophageal cancers are among the highest mortality from cancers worldwide. Microbiota has an interplaying role within the human gastrointestinal (GI) tract. Dysbiosis occurs when a disruption of the balance between the microbiota and the host happens. With this narrative review, we discuss the main alterations in the microbiome of gastroesophageal cancer, revealing its potential role in the pathogenesis, early detection, and treatment., Results: Helicobacter pylori plays a major role the development of a cascade of preneoplastic conditions ranging from atrophic gastritis to metaplasia and dysplasia, ultimately culminating in gastric cancer, while other pathogenic agents are Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, and Lactobacillus. Campylobacter species (spp.)'s role in the progression of esophageal adenocarcinoma may parallel that of Helicobacter pylori in the context of gastric cancer, with other esophageal carcinogenic agents being Escherichia coli, Bacteroides fragilis, and Fusobacterium nucleatum. Moreover, gut microbiome could significantly alter the outcomes of chemotherapy and immunotherapy. The gut microbiome can be modulated through interventions such as antibiotics, probiotics, or prebiotics intake. Fecal microbiota transplantation has emerged as a therapeutic strategy as well., Conclusions: Nowadays, it is widely accepted that changes in the normal gut microbiome causing dysbiosis and immune dysregulation play a role gastroesophageal cancer. Different interventions, including probiotics and prebiotics intake are being developed to improve therapeutic outcomes and mitigate toxicities associated with anticancer treatment. Further studies are required in order to introduce the microbiome among the available tools of precision medicine in the field of anticancer treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis., Methods: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced., Results: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections., Conclusion: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients., (© 2024. The Author(s).)

Chronic constipation is one of the common gastrointestinal disorders, with an incidence rate that is gradually increasing yearly and becoming an important chronic disease that affects people's health and quality of life. In recent years, significant progress has been made in the basic and clinical research of chronic constipation, especially the gut microbiota therapy methods have received increasing attention. Therefore, under the initiative of the Parenteral and Enteral Nutrition Branch of the Chinese Medical Association, Chinese Society for the Promotion of Human Health Science and Technology, and Committee on Gut Microecology and Fecal Microbiota Transplantation, experts from relevant fields in China have been organized to establish the " Chinese Expert Consensus on the Clinical Diagnosis and Treatment of Gut Microecology in Chronic Constipation (2024 Edition) " committee. Focusing on the dysbiosis of gut microbiota, the indications for gut microbiota therapy, and the protocols for fecal microbiota transplantation, 16 consensus opinions were proposed based on the review of domestic and international literature and the clinical experience of experts, aiming to standardize the clinical application of gut microbiota in chronic constipation.

Human papillomavirus (HPV) is a sexually transmitted virus, which infects approximately 80% of all men and women at some time in their lives. Usually, the infection is resolved successfully by the body's immune system. Persistent infection with high-risk HPV (hrHPV) is necessary but not sufficient for cervical cancer development, and additional factors, such as the vaginal microbiome (vaginome), are thought to be involved. The aim of this study is to investigate whether either vaginal dysbiosis (imbalance in vaginal bacterial composition) or sexually transmitted pathogens, e.g., Chlamydia trachomatis (CT), are possible cofactors for hrHPV infection and HPV-induced cervical dysplasia in asymptomatic women attending the Dutch Cervical Cancer Screening Program. In this study, 492 hrHPV-positive and 500 hrHPV-negative cervical smears from women attending the Screening Program were included. Age and cytology were known for the hrHPV-positive samples. All cervical smears were diluted in Aptima ® specimen transfer medium and tested with Aptima ® transcription-mediated amplification assays targeting CT , Neisseria gonorrhoeae (NG) , Mycoplasma genitalium (MG) , Candida spp. (CS), C. glabrata (CG) , Trichomonas vaginalis (TV), and bacterial vaginosis (BV). The prevalences of CT, NG, MG, CS, CG, TV, and BV in this cohort were found to be 1.9%, 0.0%, 1.7%, 5.4%, 1.4%, 0.1%, and 27.2%, respectively. When comparing HPV groups, it was found that CT, MG, and BV had a significantly higher prevalence in hrHPV-positive smears as compared with hrHPV-negative samples (for all p < 0.001). No significant differences were found when comparing different age groups and cytology outcomes. In conclusion, vaginal dysbiosis seems associated with hrHPV infection in women attending the Dutch Cervical Cancer Screening Program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Loonen, Verhagen, Luijten-de Vrije, Lentjes-Beer, Huijsmans and van den Brule.)

Acute leukemia (AL), one of the hematological malignancies, shows high heterogeneity. Tremendous progresses are achieved in treating AL with novel targeted drugs and allogeneic hematopoietic stem cell transplantation, there are numerous issues including pathogenesis, early diagnosis, and therapeutic efficacy of AL to be solved. In recent years, an increasing number of studies regarding microbiome have shed more lights on the role of gut microbiota in promoting AL progression. Mechanisms related to the role of gut microbiota in enhancing AL genesis are summarized in the present work, especially on critical pathways like leaky gut, bacterial dysbiosis, microorganism-related molecular patterns, and bacterial metabolites, resulting in AL development. Additionally, the potential of gut microbiota as the biomarker for early AL diagnosis is discussed. It also outlooks therapies targeting gut microbiota for preventing AL development., (© 2023 Wiley-VCH GmbH.)

Background: There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity., Methods: This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith's phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances., Results: Shannon and Faith's phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE., Conclusions: Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The second leading mortality cause in the world is cancer, making it a critical issue that impacts human health. As a result, scientists are looking for novel biomarkers for cancer detection. The oral microbiome, made up of approximately 700 species-level taxa, is a significant source for discovering novel biomarkers. In this review, we aimed to prepare a summary of research that has investigated the association between the oral microbiome and gastrointestinal cancers., Methods: We searched online scientific datasets including Web of Science, PubMed, Scopus, and Google Scholar. Eligibility criteria included human studies that reported abundances of the oral microbiome, or its diagnostic/prognostic performance in patients with gastrointestinal cancers., Results: Some phyla of the oral microbiome have a relationship with cancers. Some particular phyla of the oral microbiome that may be related to gastrointestinal cancers consist of Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria. Changes in the abundances of Porphyromonas, Fusobacterium, Prevotella, and Veillonella are correlated with carcinogenesis, and may be used for distinguishing cancer patients from healthy subjects. Oral, colorectal, pancreatic, and esophageal cancers are the most important cancers related to the oral microbiome., Conclusion: The results of this study may help future research to select bacteria as an early diagnostic or prognostic biomarker of gastrointestinal cancer. Given the current state of our knowledge, additional research is required to comprehend the multiplex processes underlying the role of bacterial microbiota upon cancer progression and to characterize the complex microbiota-host interaction network., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dysbiosis and weakened gastrointestinal barrier function have been identified as potential regulators of Chronic Kidney Disease (CKD). The complex connection among gut micro biota and CKD is provided in this study, with particular attention to how inflammation contributes to the CKD path physiology. It establishes the inverse association between CKD and gut microbial dysbiosis by exploring the collision of CKD about the organization and capabilities of the gut micro biota. The possibility of new diagnostic tools in measuring the dynamic changes within the gut microbial ecology illustrates the importance of accurately diagnosing gut micro biota abnormalities in CKD. Additionally, the study explores the targeted medicines that focus on gut micro biota in CKD. Using data from both human clinical trials and rat models, the study demonstrates the variety of therapeutic approaches and their ability to limit the rate of development of CKD and its accompanying problems. The study we performed was based on the Preferred Reporting Items for Systematic reviews and Meta Analyses (PRISMA) approach. The findings show the significance of investigating the relationship between gut micro biota and CKD, paving up the possibility for new therapeutic strategies to improve the patient outcomes and quality of life. The present understanding of CKD-induced modifications to the gut micro biota and the ensuing effects on gastrointestinal health, emphasizing studies, will be highlighted in this review.

Practical and affordable tools to screen intestinal dysbiosis are needed to support clinical decision making. Our study aimed to design a new subjective screening tool for the risk of intestinal dysbiosis from a previously described nonvalidated questionnaire (DYS/FQM) and based on subjective and objective data. A total of 219 individuals comprised the chronic diseases (CD; n = 167) and healthy control (HC; 52 subjects) groups. Sociodemographic, anthropometric, body composition, lifestyle, past history, intestinal health, and dietary data were collected. The gut microbiota (GM) profile was assessed from fecal samples using the 16S rRNA sequencing. Scores for the new tool (Dys-R Questionnaire) were assigned using discrete optimization techniques. The association between Dys-R scores and dysbiosis risk was assessed through correlation, simple linear models, sensitivity, specificity, as well as positive and negative predictive values. We found significant differences in the Chao1 Index between CD and HC groups (adjusted p -value = 0.029), highlighting lower GM richness as the primary marker for intestinal dysbiosis. DYS/FQM showed poor performance in identifying poor GM richness. Dys-R exhibited a 42% sensitivity, 82% specificity, 79% positive predictive value (PPV), and 55% negative predictive value (NPV) to identify poor GM richness. The new Dys-R questionnaire showed good performance in ruling out dysbiosis.

Objectives: The relationship between head and neck squamous cell carcinoma (HNSCC) and the oral microbiome has been drawn in various studies. Microbial diversities, microbiome profiles, metagenomic analysis, and host-pathogen interactions were collected from these studies to highlight similarities and account for inconsistencies. We also evaluate the possible clinical applications of the microbiome regarding screening and diagnosis of HNSCC., Methods: Systematic analysis of studies regarding HNSCC and the microbiome was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Articles were retrieved from four databases (PubMed, ScienceDirect, CUHK Full-Text Journals, and Cochrane database) and were screened using predefined criteria., Results: Twenty studies were chosen after screening for full-text review. α-diversity comparison was inconsistent whereas β-diversity between HNSCC and normal samples showed distinct clustering. Microbial dysbiosis characterized by change in the relative abundances of several bacterial species were also seen in HNSCC patients. At a phylum level, inconsistencies were seen between studies using HNSCC tumor tissue samples and saliva samples. At a genus level, Fusobacterium, Peptostreptococcus, Alloprevotella, Capnocytophaga, Catonella, and Prevotella were differentially enriched in HNSCC while Streptococcus, Actinomyces Veillonella, and Rothia were differentially depleted. Co-occurrence network analysis revealed a positive correlation of HNSCC with periodontal pathogens and a negative correlation with commensal bacteria. Metagenomic analysis of microbiota revealed a differential enrichment of pro-inflammatory genomic pathways which was consistent across various studies. Microbial dysbiosis was applied in clinical use as a tool for HNSCC screening. Random-forest analysis was adopted to differentiate between tumor and normal tissue, at 95.7% and 70.0% accuracies respectively in two studies. Microbial dysbiosis index was also used to predict prognosis., Conclusions: Oral microbial dysbiosis could be a promising tool for HNSCC screening and diagnosis. However, more research should be conducted pertaining to clinical applications to improve diagnostic accuracy and explore other clinical uses., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Human blood contains low biomass of circulating microbial cell-free DNA (cfmDNA) that predominantly originates from bacteria. Numerous studies have detected circulating cfmDNA in patients with infectious and non-infectious diseases, and in healthy individuals. Remarkable differences were found in the microbial composition of healthy subjects and patients compared to cohorts with various diseases or even patients with diversified prognoses, implying that these alterations may be associated with disease development. Although the function of circulating cfmDNA needs to be elucidated (whether it acts as a bystander of dysbiosis or a key player in disease development), several studies have demonstrated its potential as a non-invasive biomarker that may improve diagnosis and treatment efficacy. The origin of circulating cfmDNA is still the subject of much deliberation, but studies have identified members of various microbiome niches, including the gut, oral cavity, airways, and skin. Further studies investigating the origin and function of circulating cfmDNA are needed. Moreover, low-biomass microbiome studies are prone to contamination, therefore stringent negative experimental control reactions and decontamination frameworks are advised in order to detect genuine circulating cfmDNA.

The gut microbiome serves as a signaling hub that integrates environmental inputs with genetic and immune signals to influence the host's metabolism and immunity. Gut bacteria are intricately connected with human health and disease state, with specific bacteria species driving the characteristic dysbiosis found in gastrointestinal conditions such as inflammatory bowel disease (IBD); thus, gut bacteria changes could be harnessed to improve IBD diagnosis, prognosis, and treatment. The advancement in next-generation sequencing techniques such as 16S rRNA and whole-genome shotgun sequencing has allowed the exploration of the complexity of the gut microbial ecosystem with high resolution. Current microbiome data is promising and appears to perform better in some studies than the currently used fecal inflammation biomarker, calprotectin, in predicting IBD from healthy controls and irritable bowel syndrome (IBS). This study reviews current data on the differential potential of gut bacteria within IBD cohorts, and between IBD and other gastrointestinal diseases.

Dysbiosis of gut microbial community is associated with the pathogenesis of CD and may serve as a promising noninvasive diagnostic tool. We aimed to compare the performances of the microbial markers of different biological levels by conducting a multidimensional analysis on the microbial metagenomes of CD. We collected fecal metagenomic datasets generated from eight cohorts that altogether include 870 CD patients and 548 healthy controls. Microbial alterations in CD patients were assessed at multidimensional levels including species, gene, and SNV level, and then diagnostic models were constructed using artificial intelligence algorithm. A total of 227 species, 1047 microbial genes, and 21,877 microbial SNVs were identified that differed between CD and controls. The species, gene, and SNV models achieved an average AUC of 0.97, 0.95, and 0.77, respectively. Notably, the gene model exhibited superior diagnostic capability, achieving an average AUC of 0.89 and 0.91 for internal and external validations, respectively. Moreover, the gene model was specific for CD against other microbiome-related diseases. Furthermore, we found that phosphotransferase system (PTS) contributed substantially to the diagnostic capability of the gene model. The outstanding performance of PTS was mainly explained by genes celB and manY, which demonstrated high predictabilities for CD with metagenomic datasets and was validated in an independent cohort by qRT-PCR analysis. Our global metagenomic analysis unravels the multidimensional alterations of the microbial communities in CD and identifies microbial genes as robust diagnostic biomarkers across geographically and culturally distinct cohorts.

The occurrence of inflammatory bowel disease (IBD) is related to environmental factors, host immune status, genetic susceptibility and flora imbalance. With the development of sequencing technologies, the relationship between intestinal microbiota and IBD has been further studied and confirmed in many aspects. This article summarizes the characteristics of microbiota alterations in patients with IBD, as well as the role and mechanisms of microbiota dysbiosis in the onset and development of IBD, and discusses the research status of therapies based on intestinal microbiota, prospecting the future of intestinal flora in the prevention, diagnosis, treatment and prognosis of IBD.

Background: Spontaneous bacterial peritonitis (SBP) is a severe infection in cirrhotic patients that requires early diagnosis to improve the long-term outcome. Alterations in the gut microbiota have been shown to correlate with the development and progression of liver cirrhosis. However, the relationship between SBP and gut microbiota remains unknown., Methods: In this study, we applied 16S rRNA pyrosequencing of feces to ascertain possible links between the gut microbiota and SBP. We recruited 30 SBP patients, 30 decompensated cirrhotic patients without SBP (NSBP) and 30 healthy controls. Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt., Results: The composition of the gut microbiota in the SBP patients differed remarkably from that in the NSBP patients and healthy individuals. The microbial richness was significantly decreased, while the diversity was increased in the SBP patients. Thirty-four bacterial taxa containing 15 species, mainly pathogens such as Klebsiella pneumoniae , Serratia marcescens and Prevotella oris , were dominant in the SBP group, while 42 bacterial taxa containing 16 species, especially beneficial species such as Faecalibacterium prausnitzii , Methanobrevibacter smithii and Lactobacillus reuteri , were enriched in the NSBP group. Notably, we found that 18 gene functions of gut microbiota were different between SBP patients and NSBP patients, which were associated with energy metabolism and functional substance metabolism. Five optimal microbial markers were determined using a random forest model, and the combination of Lactobacillus reuteri , Rothia mucilaginosa , Serratia marcescens , Ruminococcus callidus and Neisseria mucosa achieved an area under the curve (AUC) value of 0.8383 to distinguish SBP from decompensated cirrhosis., Conclusions: We described the obvious dysbiosis of gut microbiota in SBP patients and demonstrated the potential of microbial markers as noninvasive diagnostic tools for SBP at an early stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Lv, Lv, Shi, Huang, Chen and Shi.)

Acne vulgaris (AV) and rosacea are two of the most common dermatoses diagnosed and managed by dermatologists.1,2 Despite this and our improved understanding of the unique pathogenesis of each, there has been little focus on general skin care and how it may affect physiologic functioning of the epidermis until recently.

Microbiota studies have reported changes in the microbial composition of the breast upon cancer development. However, results are inconsistent and limited to the later phases of cancer development (after diagnosis). We analyzed and compared the resident bacterial taxa of histologically normal breast tissue (healthy, H, n  = 49) with those of tissues donated prior to (prediagnostic, PD, n  = 15) and after (adjacent normal, AN, n  = 49, and tumor, T, n  = 46) breast cancer diagnosis ( n total = 159). DNA was isolated from tissue samples and submitted for Illumina MiSeq paired-end sequencing of the V3-V4 region of the 16S gene. To infer bacterial function in breast cancer, we predicted the functional bacteriome from the 16S sequencing data using PICRUSt2. Bacterial compositional analysis revealed an intermediary taxonomic signature in the PD tissue relative to that of the H tissue, represented by shifts in Bacillaceae , Burkholderiaceae , Corynebacteriaceae , Streptococcaceae , and Staphylococcaceae . This compositional signature was enhanced in the AN and T tissues. We also identified significant metabolic reprogramming of the microbiota of the PD, AN, and T tissue compared with the H tissue. Further, preliminary correlation analysis between host transcriptome profiling and microbial taxa and genes in H and PD tissues identified altered associations between the human host and mammary microbiota in PD tissue compared with H tissue. These findings suggest that compositional shifts in bacterial abundance and metabolic reprogramming of the breast tissue microbiota are early events in breast cancer development that are potentially linked with cancer susceptibility. IMPORTANCE The goal of this study was to determine the role of resident breast tissue bacteria in breast cancer development. We analyzed breast tissue bacteria in healthy breast tissue and breast tissue donated prior to (precancerous) and after (postcancerous) breast cancer diagnosis. Compared to healthy tissue, the precancerous and postcancerous breast tissues demonstrated differences in the amounts of breast tissue bacteria. In addition, breast tissue bacteria exhibit different functions in pre-cancerous and post-cancerous breast tissues relative to healthy tissue. These differences in function are further emphasized by altered associations of the breast tissue bacteria with gene expression in the human host prior to cancer development. Collectively, these analyses identified shifts in bacterial abundance and metabolic function (dysbiosis) prior to breast tumor diagnosis. This dysbiosis may serve as a therapeutic target in breast cancer prevention.

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn's disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium&#95;animalis, and Muribaculaceae-previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of gut microbiota in COVID-19 patients compared with healthy individuals may have potential value as a diagnostic and/or prognostic biomarker for the disease. Also, therapeutic interventions affecting gut microbial flora may open new horizons in the treatment of COVID-19 patients and accelerating their recovery., Methods: A systematic search was conducted for relevant studies published from December 2019 to December 2021 using Pubmed/Medline, Embase, and Scopus. Articles containing the following keywords in titles or abstracts were selected: "SARS-CoV-2" or "COVID-19" or "Coronavirus Disease 19" and "gastrointestinal microbes" or "dysbiosis" or "gut microbiota" or "gut bacteria" or "gut microbes" or "gastrointestinal microbiota"., Results: Out of 1,668 studies, 22 articles fulfilled the inclusion criteria and a total of 1,255 confirmed COVID-19 patients were examined. All included studies showed a significant association between COVID-19 and gut microbiota dysbiosis. The most alteration in bacterial composition of COVID-19 patients was depletion in genera Ruminococcus , Alistipes , Eubacterium , Bifidobacterium , Faecalibacterium , Roseburia , Fusicathenibacter , and Blautia and enrichment of Eggerthella , Bacteroides , Actinomyces , Clostridium , Streptococcus , Rothia , and Collinsella. Also, some gut microbiome alterations were associated with COVID-19 severity and poor prognosis including the increment of Bacteroides , Parabacteroides , Clostridium , Bifidobacterium , Ruminococcus , Campylobacter , Rothia , Corynebacterium , Megasphaera , Enterococcus , and Aspergillus spp. and the decrement of Roseburia , Eubacterium , Lachnospira , Faecalibacterium , and the Firmicutes/Bacteroidetes ratio., Conclusion: Our study showed a significant change of gut microbiome composition in COVID-19 patients compared with healthy individuals. This great extent of impact has proposed the gut microbiota as a potential diagnostic, prognostic, and therapeutic strategy for COVID-19. There is much evidence about this issue, and it is expected to be increased in near future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Farsi, Tahvildari, Arbabi, Vazife, Sechi, Shahidi Bonjar, Jamshidi, Nasiri and Mirsaeidi.)

Introduction: Measurement of breath hydrogen (H 2 ) and methane (CH 4 ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline., Methods: This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of H 2 -CH 4 -breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria., Results: The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro-cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H 2 -CH 4 -breath tests in these indications and recommends approaches to mitigate these issues., Conclusion: This clinical practice guideline should facilitate pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Type 2 diabetes (T2D) is a major public health problem, and gut microbiota dysbiosis has been implicated in the emergence of T2D in humans. Dietary interventions can indirectly influence the health status of patients with type 2 diabetes through their modulatory effects on the intestinal microbiota. In recent years, fecal microbiota transplantation is becoming familiar as a new medical treatment that can rapidly improve intestinal health. We conducted a 90-day controlled open-label trial to evaluate the health improvement ability of a specially designed diet, and the diet combined with fecal microbiota transplantation (FMT). According to our study, both diet and diet plus FMT treatments showed great potential in controlling blood glucose and blood pressure levels. Sequencing the V4 region of 16S rRNA gene on the Illumina MiniSeq platform revealed a shift of intestinal microbial community in T2D patients, and the changes were also observed in response to the treatments. FMT changed the gut microbiota more quickly than diet. Beneficial bacterium, such as Bifidobacterium, increased along the study and was negatively correlated with blood glucose, blood pressure, blood lipid and BMI. Sulfate-reducing bacteria (SRB), Bilophila and Desulfovibrio, decreased significantly after treatment, showed a positive correlation with blood glucose indices. Thus, the specially designed diet is beneficial to improve blood glucose control in diabetic patients, it also showed the potential to reverse dyslipidemia and dysarteriotony., (© 2022. The Author(s).)

Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray-Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray-Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies., Competing Interests: The authors have declared that no competing interests exist.

Modulation of commensal gut microbiota is increasingly recognized as a promising strategy to reduce mortality in patients with malignant diseases, but monitoring for dysbiosis is generally not routine clinical practice due to equipment, expertise and funding required for sequencing analysis. A low-threshold alternative is microbial diversity profiling by single-cell flow cytometry (FCM), which we compared to 16S rRNA sequencing in human fecal samples and employed to characterize longitudinal changes in the microbiome composition of patients with aggressive B-cell non-Hodgkin lymphoma undergoing chemoimmunotherapy. Diversity measures obtained from both methods were correlated and captured identical trends in microbial community structures, finding no difference in patients' pretreatment alpha or beta diversity compared to healthy controls and a significant and progressive loss of alpha diversity during chemoimmunotherapy. Our results highlight the potential of FCM-based microbiome profiling as a reliable and accessible diagnostic tool that can provide novel insights into cancer therapy-associated dysbiosis dynamics.

Background: Although intestinal fungi are known to interact with the immune system, the relationship between intestinal fungi and childhood celiac disease (CeD), an immune-mediated condition, has rarely been reported., Aims: The aim of this study was to describe gut fungal profiles in a cohort of children with new-onset CeD., Methods: Mucosal and fecal samples were collected from children with CeD and controls and subjected to metagenomics analysis of fungal microbiota communities. DNA libraries were sequenced using Illumina HiSeq platform 2 × 150 bp. Bioinformatic analysis was performed to quantify the relative abundance of fungi. Shannon alpha diversity metrics and beta diversity principal coordinate (PCo) analyses were calculated, and DESeq tests were performed between celiac and non-celiac groups., Results: Overall more abundant taxa in samples of children with CeD included Tricholomataceae, Saccharomycetaceae, Saccharomycetes Saccharomyces cerevisiae, and Candida, whereas less abundant taxa included Pichiaceae, Pichia kudriavzevii, Pneumocystis, and Pneumocystis jirovecii. Alpha diversity between CeD and control individuals did not differ significantly, and beta diversity PCo analysis showed overlap of samples from CeD and controls for both fecal or mucosal samples; however, there was a clear separation between mucosal and fecal overall samples CONCLUSIONS: We report fungal dysbiosis in children with CeD, suggesting a possible role in the pathogenesis of CeD. Further larger, controlled, prospective and longitudinal studies are needed to verify the results of this study and clarify the functional role of fungi in CeD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colorectal cancer (CRC) is ranked as the second most common cause of cancer deaths and the third most common cancer globally. It has been described as a 'silent disease' which is often easily treatable if detected early-before progression to carcinoma. Colonoscopy, which is the gold standard for diagnosis is not only expensive but is also an invasive diagnostic procedure, thus, effective and non-invasive diagnostic methods are urgently needed. Unfortunately, the current methods are not sensitive and specific enough in detecting adenomas and early colorectal neoplasia, hampering treatment and consequently, survival rates. Studies have shown that imbalances in such a relationship which renders the gut microbiota in a dysbiotic state are implicated in the development of adenomas ultimately resulting in CRC. The differences found in the makeup and diversity of the gut microbiota of healthy individuals relative to CRC patients have in recent times gained attention as potential biomarkers in early non-invasive diagnosis of CRC, with promising sensitivity, specificity and even cost-effectiveness. This review summarizes recent studies in the application of these microbiota biomarkers in early CRC diagnosis, limitations encountered in the area of the faecal microbiota studies as biomarkers for CRC, and future research exploits that address these limitations., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: The aim of this paper was to discuss the potency of gut microbiome as a non-invasive predictive biomarker for early detection of pancreatic cancer and hepatocellular carcinoma., Materials and Methods: We analysed the available up-to-date literature (PubMed, Embase, Google Scholar databases) regarding the link between gut microbiome and early detection of pancreatic cancer, as well as hepatocellular carcinoma. The following search linked to gut microbiome and aforementioned cancers was used: 'gut microbiome', 'gut microbiota', 'pancreatic cancer', 'pancreatic ductal adenocarcinoma', hepatocellular carcinoma', 'microbial biomarkers', 'fungal microbiota', 'mycobiota'.  The search was conducted in English., Results: The association between gut microbiota imbalance and development of pancreatic cancer and hepatocellular carcinoma has been recognized during last several years. The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma, whose carcinogenesis is strongly related to oral microbial dysbiosis, H. pylori infection, bactibilia, hepatotropic viruses, and intrapancreatic microbiota. It is known that gut-liver axis exists and may affect hepatocarcinogenesis. Currently, the treatment strategies of these cancers are strongly limited and there are not well-recognized screening tools to early diagnose them. The growing attention towards the use of gut microbiome as a predictive non-invasive biomarker to detect pancreatic cancer and hepatocellular carcinoma in early stage has been observed., Conclusions: To conclude, the field regarding the link between gut microbiome as a non-invasive biomarkers and early detection of pancreatic cancer and hepatocellular carcinoma exists, however, it is not well-investigated. Additionally, many of the studies were conducted with small sample sizes, whereas biomarkers are ethnicity-dependent and should be validated in wide range of populations. Nevertheless, these aspects are promising and open up new diagnostic options.

The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Through 16S rRNA gene sequencing, 728 samples are collected to identify microbial markers, and an independent cohort of 310 samples is used to validate the results. Furthermore, species-level and functional analysis are performed by metagenome sequencing using 200 samples. Gut microbial diversity is increased in yCRC. Flavonifractor plautii is an important bacterial species in yCRC, while genus Streptococcus contains the key phylotype in the old-onset colorectal cancer. Functional analysis reveals that yCRC has unique characteristics of bacterial metabolism characterized by the dominance of DNA binding and RNA-dependent DNA biosynthetic process. The random forest classifier model achieves a powerful classification potential. This study highlights the potential of the gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with yCRC., (© 2021. The Author(s).)

Background: The gut and oral microbiome have independently been shown to be associated with inflammatory bowel disease (IBD). However, it is not known to what extent gut and oral microbial disease markers converge in terms of their composition in IBD. Further, the spatial and temporal variation within the oral microenvironments of IBD remain to be elucidated., Patients and Methods: We used a prospectively recruited cohort of patients with IBD (n = 47) and unrelated healthy control patients (n = 18) to examine the spatial and temporal distribution of microbiota within the various oral microenvironments, represented by saliva, tongue, buccal mucosa, and plaque, and compared them with stool. Microbiome characterization was performed using 16S rRNA gene sequencing., Results: The oral microbiome displayed IBD-associated dysbiosis, in a site- and taxa-specific manner. Plaque samples depicted a relatively severe degree of dysbiosis, and the disease-associated dysbiotic bacterial groups were predominantly the members of the phylum Firmicutes. Our 16S rRNA gene analyses show that oral microbiota can distinguish patients with IBD from healthy control patients, with salivary microbiota performing the best, closely matched by stool and other oral sites. Longitudinal profiles of microbial composition suggest that some taxa are more consistently perturbed than others, preferentially in a site-dependent fashion., Conclusions: Collectively, these data indicate the potential of using oral microbial profiles in screening and monitoring patients with IBD. Furthermore, these results support the importance of spatial and longitudinal microbiome sampling to interpret disease-associated dysbiotic states and eventually to gain insights into disease pathogenesis., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Children with acute lymphoblastic leukemia (ALL) undergoing chemotherapy experience a relatively high risk of infection. And the disturbance of gut microbiota is generally believed to impair intestinal barrier function and may induce bacterial infections and inflammation. The study aimed to investigate the alterations in the gut microbiota and assess its relationship with chemotherapy-induced pneumonia in pediatric ALL patients., Methods: We conducted a case-control study with 14 cases affected by pneumonia and 44 unaffected subjects and characterized the physiological parameters and gut microbiota by microarray-based technique., Results: There were significant differences in α- and β-diversity in the affected group compared with the control group. At species level, the LEfSe analysis revealed that Enterococcus malodoratus, Ochrobactrum anthropi and Actinomyces cardiffensis were significantly abundant in the affected subjects. A receiver operating characteristic (ROC) curve yielded the area under the curve (AUC) of 0.773 for classification between the two groups. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the bacterial secretion system were more enriched in the affected group than in the control group., Conclusions: Gut microbiota alteration was associated with chemotherapy-induced pneumonia in pediatric ALL patients, which provided a new perspective on the personalized clinical care of pediatric ALL., (© 2021. The Author(s).)

The human gastrointestinal tract, skin and mucosal surfaces are inhabited by a complex system of bacteria, viruses, fungi, archaea, protists, and eukaryotic parasites with predominance of bacteria and bacterial viruses (bacteriophages). Collectively these microbes form the microbiota of the microecosystem of humans. Recent advancement in technologies for nucleic acid isolation from various environmental samples, feces and body secretions and advancements in shotgun throughput massive parallel DNA and RNA sequencing along with 16S ribosomal gene sequencing have unraveled the identity of otherwise unknown microbial entities constituting the human microecosystem. The improved transcriptome analysis, technological developments in biochemical analytical methods and availability of complex bioinformatics tools have allowed us to begin to understand the metabolome of the microbiome and the biochemical pathways and potential signal transduction pathways in human cells in response to microbial infections and their products. Also, developments in human whole genome sequencing, targeted gene sequencing of histocompatibility genes and other immune response associated genes by Next Generation Sequencing (NGS) have allowed us to have a better conceptualization of immune responses, and alloimmune responses. These modern technologies have enabled us to dive into the intricate relationship between commensal symbiotic and pathogenic microbiome and immune system. For the most part, the commensal symbiotic microbiota helps to maintain normal immune homeostasis besides providing healthy nutrients, facilitating digestion, and protecting the skin, mucosal and intestinal barriers. However, changes in diets, administration of therapeutic agents like antibiotics, chemotherapeutic agents, immunosuppressants etc. along with certain host factors including human histocompatibility antigens may alter the microbial ecosystem balance by causing changes in microbial constituents, hierarchy of microbial species and even dysbiosis. Such alterations may cause immune dysregulation, breach of barrier protection and lead to immunopathogenesis rather than immune homeostasis. The effects of human microbiome on immunity, health and disease are currently under intense research with cutting edge technologies in molecular biology, biochemistry, and bioinformatics along with tremendous ability to characterize immune response at single cell level. This review will discuss the contemporary status on human microbiome immune system interactions and their potential effects on health, immune homeostasis and allograft transplantation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

A mixed Chinese herbal formula, Xiao-Qing-Long-Decoction (XQLD), may contribute to sustained remission in allergic rhinitis (AR), but it is unknown which factors determine such long-term effect. Here, we aimed to identify bacterial signatures associated with sustained remission. To this end, samples from AR patients at four different times were analyzed to compare the dynamic bacterial community and structure shifts. Diversity indices Chao1 showed significant difference across different time ( p <0.05), and the Kruskal-Wallis test identified that Dialister (OTU&#95;31), Roseburia (OTU&#95;36), Bacteroides (OTU&#95;22), Bacteroides (OTU&#95;2040), and Prevotella&#95; 9 (OTU&#95;5) were the significant differential bacterial taxa ( p <0.05). These distinctive genera were significantly associated with the change of AR clinical indices and the predicted functional pathways such as PPAR signaling pathway, peroxisome, and citrate cycle (TCA cycle) ( p <0.05), indicating that they may be important bacterial signatures involving in the sustained remission in AR ( p <0.05). Besides, lower Firmicutes/Bacteroidetes (F/B) ratio at 6 months follow-up may also contribute to the long-term remission of AR. No seriously adverse events and safety concerns were observed in this study. In conclusion, XQLD is a meaningful, long-term efficient and safe medication for AR treatment. The underlying mechanisms of sustained remission in AR after XQLD treatment may be associated with the dynamic alteration of featured gut bacteria taxa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Wu, Lin, Tang, Yu, Wan, Xuan, Du, Chen and Liang.)

Method: This study included 74 Chinese male patients with HCC. They were divided into early ( n = 19), intermediate ( n = 37), and terminal ( n = 18) groups, referred to as Barcelona Clinic Liver Cancer stage 0+A, B, and C+D, respectively. Paired fecal and plasma samples were collected. Microbial composition and profiles were analyzed by 16S rRNA gene sequencing. The levels of gut damage marker (regenerating islet-derived protein 3 α (REG3 α )) and microbial translocation markers (soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), peptidoglycan recognition proteins (PGRPs)) were determined in plasma samples of patients by ELISA. Twenty plasma cytokine and chemokines were determined by Luminex., Results: In early, intermediate, and terminal groups, the abundance of the Bifidobacteriaceae family decreased significantly (3.52%, 1.55%, and 0.56%, respectively, P = 0.003), while the abundance of the Enterococcaceae family increased significantly (1.6%, 2.9%, and 13.4%, respectively, P = 0.022). Levels of REG3 α and sCD14 were markedly elevated only in the terminal group compared with the early ( P = 0.025 and P = 0.048) and intermediate groups ( P = 0.023 and P = 0.046). The level of LBP significantly increased in the intermediate ( P = 0.035) and terminal ( P = 0.025) groups compared with the early group. The PGRP levels were elevated only in the terminal group compared with the early group ( P = 0.018). The ratio of Enterococcaceae to Bifidobacteriaceae was significantly associated with the levels of REG3 α , LBP, sCD14, and PGRPs. With HCC progression, increased levels of inflammatory cytokines accompanied by a T cell-immunosuppressive response and microbial translocation were observed., Conclusion: Gut microbiota compositional and functional shift, together with elevated gut damage and microbial translocation, may promote HCC development by stimulating inflammatory response and suppressing T cell response., Competing Interests: All authors report no conflicts of interest relevant to this study., (Copyright © 2021 Nan Zhang et al.)

Objective: Periodontitis is an inflammatory disease of microbial etiology caused primarily by dysbiosis of the oral microbiota. Our aim was to compare variations in the composition of the oral microbiomes of youths with severe periodontitis according to gender., Methods: Subgingival plaque samples collected from 17 patients with severe periodontitis (11 males and 6 females) were split for 16S rRNA gene sequencing. The composition, α -diversity, and β -diversity of the patients' oral microbiomes were compared between the males and the females. Linear discriminant analysis effect size (LEfSe) was used to analyze the specific taxa enriched in the two groups. Functional profiles (KEGG pathways) were obtained using PICRUSt based on 16S rRNA gene sequencing data., Results: The Chao1 index and phylogenetic diversity whole tree were significantly higher in males than in females. The Simpson and Shannon indices were not significantly different between the two groups. β -Diversity suggested that the samples were reasonably divided into groups. The Kruskal-Wallis test based on the relative abundance of species, combined with the LEfSe analysis showed that the dominant bacteria in males were Pseudomonas and Papillibacter , whereas the dominant bacteria in women were Fusobacteriales and Tannerella . KEGG analysis predicted that the variation in the oral microbiome may be related to the immune system in women, whereas immune system diseases were the dominant pathway in men., Conclusion: We found sex-specific differences in the oral microbiome in a sample of youths with severe periodontitis. The differences may be related to changes in immune homeostasis and lead to a better understanding of periodontitis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Ya-Qiong Zhao et al.)

Endometriosis is a chronic, estrogen-dependent gynecological condition affecting approximately 10% of reproductive age women. The most widely accepted theory of its etiology includes retrograde menstruation. Recent reports suggest the uterus is not sterile. Thus, the refluxed menstrual effluent may carry bacteria, and contribute to inflammation, the establishment and growth of endometriotic lesions. Here, we compared and contrasted uterine bacteria (endometrial microbiota) in people with surgically confirmed presence (N = 12) or absence of endometriosis (N = 9) using next-generation 16S rRNA gene sequencing. We obtained an average of > 9000 sequence reads per endometrial biopsy, and found the endometrial microbiota of people with endometriosis was more diverse (greater Shannon Diversity Index and proportion of 'Other' taxa) than symptomatic controls (with pelvic pain, surgically confirmed absence of endometriosis; diagnosed with other benign gynecological conditions). The relative abundance of bacterial taxa enriched in the endometrial microbiota of people with endometriosis belonged to the Actinobacteria phylum (Gram-positive), Oxalobacteraceae (Gram-negative) and Streptococcaceae (Gram-positive) families, and Tepidimonas (Gram-negative) genus, while those enriched in the symptomatic controls belonged to the Burkholderiaceae (Gram-negative) family, and Ralstonia (Gram-negative) genus. Taken together, results suggest the endometrial microbiota is perturbed in people with endometriosis., (© 2021. The Author(s).)

Background: Hypertension (HTN) is frequently linked with depression (DEP) in adults with cardiovascular disease (CVD), yet the underlying mechanism and successful management remain elusive. We approached this knowledge gap through the lens that humans are eukaryote-prokaryote "meta-organisms," such that cardiovascular disease dysregulation is a mosaic disorder involving dysbiosis of the gut. We hypothesized that patients diagnosed with hypertension plus depression harbor a unique gut microbial ecology with attending functional genomics engaged with their hosts' gut/brain axis physiology., Methods: Stool microbiome DNA was analyzed by whole metagenome shotgun sequencing in 54 subjects parsed into cohorts diagnosed with HTN only (N = 18), DEP only (N = 7), DEP plus HTN (DEP-HTN) (N = 8), or reference subjects with neither HTN nor DEP (N = 21). A novel battery of machine-learning multivariate analyses of de-noised data yielded effect sizes and permutational covariance-based dissimilarities that significantly differentiated the cohorts (false discovery rate (FDR)-adjusted P ≤ .05); data clustering within 95% confidence interval)., Results: Metagenomic significant differences extricated the four cohorts. Data of the cohort exhibiting DEP-HTN were germane to the interplay of central control of blood pressure concomitant with the neuropathology of depressive disorders. DEP-HTN gut bacterial community ecology was defined by co-occurrence of Eubacterium siraeum, Alistipes obesi, Holdemania filiformis, and Lachnospiraceae bacterium 1.1.57FAA with Streptococcus salivariu. The corresponding microbial functional genomics of DEP-HTN engaged pathways degrading GABA and beneficial short chain fatty acids (SCFA), and are associated with enhanced sodium absorption and inflammasome induction., Conclusions: These data suggest a new putative endotype of hypertension, which we denote "depressive-hypertension" (DEP-HTN), for which we posit a model that is distinctive from either HTN alone or DEP alone. An "endotype" is a subtype of a heterogeneous pathophysiological mechanism. The DEP-HTN model incorporates a unique signature of microbial taxa and functional genomics with crosstalk that putatively intertwines host pathophysiology involving the gastrointestinal tract with disruptions in central control of blood pressure and mood. The DEP-HTN endotype model engages cardiology with gastroenterology and psychiatry, providing a proof-of-concept foundation to explore future treatments, diagnosis, and prevention of HTN-coupled mood disorders., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder companied with neuroendocrine and metabolic disorders. Gut microbiota has been implicated to play a key role in metabolic diseases and the production of neurotransmitters. Previous studies have reported the alterations in the gut microbiota of PCOS patients and animal models, however, most of the articles did not take the effect of age or diet on gut microbiota into account. The aim of this study was to identify the differential gut microbial species in PCOS patients compared with age and BMI-matched healthy control women., Methods: We performed physical examinations and dietary survey in 20 women with PCOS (lean PCOS, PL, n = 10; overweight PCOS, PO, n = 10) and 20 healthy control women (lean control, CL, n = 10; overweight control, CO, n = 10), and collected the blood on the days 1-3 of the menstrual cycle for the measurement of endocrine and metabolic profiles, and inflammatory factors; and collected the feces in non-menstrual period to investigate the composition of gut microbiota by sequencing the V4 region of the 16S rDNA gene in fecal samples. The correlations between clinical parameters and the differential species were evaluated., Results: Dietary analysis showed that the intake of dietary fiber, vitamin D were significantly decreased in PCOS. For the first time, our study found an increase of gamma-aminobutyric acid (GABA)-producing species in PCOS, including Parabacteroides distasonis, Bacteroides fragilis and Escherichia coli, which significantly positively correlated with serum LH levels and LH:FSH ratios., Conclusions: GABA-producing bacteria that were increased in PCOS, including Parabacteroides distasonis, Bacteroides fragilis and Escherichia coli, showed positive relationship with serum LH levels and LH:FSH ratios. In conclusion, gut microbial dysbiosis in women with PCOS is associated with neuroendocrine changes, revealing a potential gut-brain axis in PCOS., (© 2021. Italian Society of Endocrinology (SIE).)

Background: Increasing evidence revealed that airway microbial dysbiosis was associated with increased risk of asthma, or persistent wheezing (PW). However, the role of lung microbiota in PW or wheezing recurrence remains poorly understood., Methods: In this prospective observational study, we performed a longitudinal 16S rRNA-based microbiome survey on bronchoalveolar lavage (BAL) samples collected from 35 infants with PW and 28 age-matched infants (control group). A 2-year follow-up study on these PW patients was conducted. The compositions of lower airway microbiota were analyzed at the phylum and genus levels., Results: Our study showed a clear difference in lower airway microbiota between PW children and the control group. Children with PW had a higher abundance of Elizabethkingia and Rothia, and lower abundance of Fusobacterium compared with the control group. At the end of the 2-year follow-up, 20 children with PW (57.1%) experienced at least one episode of wheezing, and 15 (42.9%) did not suffer from wheezing episodes. Furthermore, PW children with recurrence also had increased abundances of Elizabethkingia and Rothia relative to those who had no recurrence. Additionally, wheezing history, different gender, and caesarean section demonstrated a greater impact in airway microbiota compositions., Conclusion: This study suggests that the alterations of lower airway microbiota could be strongly associated with the development of wheezing, and early airway microbial changes could also be associated with wheezing recurrence later in life., (© 2021. The Author(s).)

Dysbiosis or imbalance in the gut microbiome has been correlated with the etiology of a number of diseases/disorders. Thus, gut microbial communities can potentially be utilized for assessing the health of the human gut. Although the taxonomic composition of the microbiomes is dependent on factors such as diet, lifestyle, and geography, these microbes perform a specific set of common functions in the gut. In this study, metabolic pathway-based markers (agnostic to above-mentioned factors) specific to commensals and those specific to pathogens are utilized as indicators of gut health. Furthermore, this gut health assessment requires only a small set of features rather than complete sequencing of metagenomes. The proposed scheme can also be used to design personalized biotherapeutics, depending on functional aspects observed in an individual., (© 2021 Federation of European Biochemical Societies.)