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BMC Bioinformatics Jun 2022Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that...
BACKGROUND
Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that microbial communities play in healthy and disease hosts remain largely unknown. The microbial communities are typically recorded through the taxa counts of operational taxonomic units (OTUs). The sparsity and high correlations among OTUs pose major challenges for understanding the microbiota-disease relation. Furthermore, the taxa data are structured in the sense that OTUs are related evolutionarily by a hierarchical structure.
RESULTS
In this study, we borrow the idea of super-variant from statistical genetics, and propose a new concept called super-taxon to exploit hierarchical structure of taxa for microbiome studies, which is essentially a combination of taxonomic units. Specifically, we model a genus which consists of a set of OTUs at low hierarchy and is designed to reflect both marginal and joint effects of OTUs associated with the risk of CRC to address these issues. We first demonstrate the power of super-taxon in detecting highly correlated OTUs. Then, we identify CRC-associated OTUs in two publicly available datasets via a discovery-validation procedure. Specifically, four species of two genera are found to be associated with CRC: Parvimonas micra, Parvimonas sp., Peptostreptococcus stomatis, and Peptostreptococcus anaerobius. More importantly, for the first time, we report the joint effect of Parvimonas micra and Parvimonas sp. (p = 0.0084) as well as that of Peptostrepto-coccus stomatis and Peptostreptococcus anaerobius (p = 8.21e-06) on CRC. The proposed approach provides a novel and useful tool for identifying disease-related microbes by taking the hierarchical structure of taxa into account and further sheds new lights on their potential joint effects as a community in disease development.
CONCLUSIONS
Our work shows that proposed approaches are effective to study the microbiota-disease relation taking into account for the sparsity, hierarchical and correlated structure among microbes.
Topics: Colorectal Neoplasms; Firmicutes; Humans; Microbiota; Peptostreptococcus
PubMed: 35729515
DOI: 10.1186/s12859-022-04786-9 -
Pediatric Research Jun 2022Premature adrenarche is a condition of childhood adrenal androgen excess (AAE) in the absence of gonadotropin-dependent puberty, and has been linked to insulin...
BACKGROUND
Premature adrenarche is a condition of childhood adrenal androgen excess (AAE) in the absence of gonadotropin-dependent puberty, and has been linked to insulin resistance and progression to metabolic syndrome. Microbial dysbiosis is associated with progression of inflammatory states and chronic diseases. Here, we aimed to examine the salivary microbiomes of children with AAE and assess the relationship with adrenal androgens and metabolic parameters.
METHODS
In a prospective cross-sectional study of children with AAE and healthy controls, adrenal and metabolic parameters were characterized and salivary microbiome was profiled using V3-V4 16S rDNA gene amplicon sequencing.
RESULTS
There was increased α-diversity in AAE (5 M, 15 F) compared to controls (3 M, 8 F), with positive correlation of 11OHA4, 11KA4, testosterone, androstenedione, DHEA, and DHEAS. Subanalyses showed increased α-diversity in both overweight/obese AAE and normal weight AAE compared to normal weight controls. Genus Peptostreptococcus, Veillonella, and Streptococcus salivarius were increased in normal weight AAE. Genus Prevotella, Abiotrophia, and Neisseria were increased in overweight/obese AAE.
CONCLUSION
These pilot data demonstrate differences in salivary microbiome profiles of children with and without AAE. Further studies are needed to assess the causal relationships between adrenal androgens, metabolic dysfunction, and salivary microbiome composition.
IMPACT
This study is the first to report the salivary microbiome of prepubertal children with adrenal androgen excess (AAE). α-Diversity is increased in the salivary microbiome of children with AAE independent of weight status, and in this study cohort several serum androgens are positively associated with α-diversity. Several taxa that have been associated with periodontal disease and inflammation are found to be significantly increased in AAE.
Topics: Androgens; Child; Cross-Sectional Studies; Dehydroepiandrosterone; Humans; Microbiota; Obesity; Overweight; Prospective Studies
PubMed: 34341500
DOI: 10.1038/s41390-021-01661-w -
Head & Neck Aug 2023The relationship between head and neck squamous cell carcinoma (HNSCC) and the oral microbiome has been drawn in various studies. Microbial diversities, microbiome... (Review)
Review
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.
Topics: Humans; Bacteria; Dysbiosis; Head and Neck Neoplasms; Microbiota; Squamous Cell Carcinoma of Head and Neck
PubMed: 37249085
DOI: 10.1002/hed.27422 -
Current Pharmaceutical Design 2021Interest in indolic structure metabolites, including a number of products of microbial biotransformation of the aromatic amino acid tryptophan, is increasingly growing.... (Review)
Review
Interest in indolic structure metabolites, including a number of products of microbial biotransformation of the aromatic amino acid tryptophan, is increasingly growing. The review prepared by a team of authors is based on in-depthscrutiny of data available in PubMed, Scopus, Cyberleninka, Clinical Trials, and Cochrane Library, eventually narrowing the search to a set of keywords such as tryptophan metabolites; plasma metabolomics profiling; metabolomics fingerprinting; gas-, liquid chromatography mass spectrometry; serotonin; melatonin; tryptamine; indoxyl sulfate; indole-3-acetic acid; indole-3-propionic acid; 5-hydroxyindole-3-acetic acid; gut microbiota and microbial metabolites. It provides a summary that outlines the pattern of changes in the level of indolic structure metabolites in a number of diseases and deals with the data from the field of human microbiota metabolites. In modern experimental studies, including the use of gnotobiological (germ-free) animals, it has been convincingly proved that the formation of tryptophan metabolites such as indole-3-acetic acid, indole-3-propionic acid, tryptamine, and indoxyl sulfate is associated with gut bacteria. Attention to some concentration changes of indolic compounds is due to the fact that pronounced deviations and a significant decrease of these metabolites in the blood were found in a number of serious cardiovascular, brain or gastrointestinal diseases. The literature-based analysis allowed the authors to conclude that a constant (normal) level of the main metabolites of the indolic structure in the human body is maintained by a few strict anaerobic bacteria from the gut of a healthy body belonging to the species of Clostridium, Bacteroides, Peptostreptococcus, Eubacteria, etc. The authors focus on several metabolites of the indolic structure that can be called clinically significant in certain diseases, such as schizophrenia, depression, atherosclerosis, colorectal cancer, etc. Determining the level of indole metabolites in the blood can be used to diagnose and monitor the effectiveness of a comprehensive treatment approach.
Topics: Animals; Biomarkers; Gastrointestinal Microbiome; Humans; Indoles; Noncommunicable Diseases; Tryptophan
PubMed: 33092503
DOI: 10.2174/1381612826666201022121653 -
BMC Microbiology Apr 2024Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical...
BACKGROUND
Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical stage for the early detection of lung cancer; however, the relationship between oral microbiota and PNs remains unknown.
METHODS
We conducted a 'Microbiome with pulmonary nodule series study 1' (MCEPN-1) where we compared PN patients and healthy controls (HCs), aiming to identify differences in oral microbiota characteristics and discover potential microbiota biomarkers for non-invasive, radiation-free PNs diagnosis and warning in the future. We performed 16 S rRNA amplicon sequencing on saliva samples from 173 PN patients and 40 HCs to compare the characteristics and functional changes in oral microbiota between the two groups. The random forest algorithm was used to identify PN salivary microbial markers. Biological functions and potential mechanisms of differential genes in saliva samples were preliminarily explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Groups (COG) analyses.
RESULTS
The diversity of salivary microorganisms was higher in the PN group than in the HC group. Significant differences were noted in community composition and abundance of oral microorganisms between the two groups. Neisseria, Prevotella, Haemophilus and Actinomyces, Porphyromonas, Fusobacterium, 7M7x, Granulicatella and Selenomonas were the main differential genera between the PN and HC groups. Fusobacterium, Porphyromonas, Parvimonas, Peptostreptococcus and Haemophilus constituted the optimal marker sets (area under curve, AUC = 0.80), which can distinguish between patients with PNs and HCs. Further, the salivary microbiota composition was significantly correlated with age, sex, and smoking history (P < 0.001), but not with personal history of cancer (P > 0.05). Bioinformatics analysis of differential genes showed that patients with PN showed significant enrichment in protein/molecular functions related to immune deficiency and energy metabolisms, such as the cytoskeleton protein RodZ, nicotinamide adenine dinucleotide phosphate dehydrogenase (NADPH) dehydrogenase, major facilitator superfamily transporters and AraC family transcription regulators.
CONCLUSIONS
Our study provides the first evidence that the salivary microbiota can serve as potential biomarkers for identifying PN. We observed a significant association between changes in the oral microbiota and PNs, indicating the potential of salivary microbiota as a new non-invasive biomarker for PNs.
TRIAL REGISTRATION
Clinical trial registration number: ChiCTR2200062140; Date of registration: 07/25/2022.
Topics: Humans; Saliva; RNA, Ribosomal, 16S; Microbiota; Biomarkers; Lung Neoplasms; Oxidoreductases
PubMed: 38643115
DOI: 10.1186/s12866-024-03280-x -
Gut Microbes 2022Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function,...
The duodenal mucosa associated microbiome, visceral sensory function, immune activation and psychological comorbidities in functional gastrointestinal disorders with and without self-reported non-celiac wheat sensitivity.
Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function, psychiatric comorbidities, gut-homing immune cells, and duodenal mucosa-associated microbiome (d-MAM) in FGID patients and controls with and without self-reported wheat sensitivity (SR-NCWS). We recruited 40 FGID patients and 20 controls referred by GPs for treatment. Gastrointestinal/extraintestinal symptoms, visceral sensory function, psychological comorbidities, and SR-NCWS were assessed in a standardized approach. Peripheral gut homing T-cells (CD4α4β7CCR9/CD8α4β7CCR9) were quantified, and the d-MAM was assessed by DNA sequencing for 46 subjects. Factors of bacterial genera were extracted utilizing factor analysis with varimax rotation and factors univariately associated with FGID or SR-NCWS included in a subsequent multivariate analysis of variance to identify statistically independent discriminators. Anxiety scores (p < .05) and increased symptom responses to a nutrient challenge (p < .05) were univariately associated with FGID. Gut homing T-cells were increased in FGID patients with SR-NCWS compared to other groups (p all <0.05). MANOVA revealed that anxiety (p = .03), visceral sensory function (p = 0.007), and a d-MAM factor comprise members of the , and lineages were significantly (p = .001) associated with FGID, while gut homing CD4α4 β7CCR9 T-cells were associated (p = .002) with SR-NCWS. Compared to controls, patients with and without SR-NCWS show that there are shifts in the amplicon sequence variants within specific bacterial genera between the FGID subgroups (particularly and ) as well as distinct bacterial taxa discriminatory for the two different FGID subtypes. Compared to controls, both FGID patients with and without SR-NCWS have an increased symptom response to a standardized nutrient challenge and increased anxiety scores. The FGID patients with SR-NCWS - as compared to FGID without SR-NCWS (and controls without SR-NCWS) - have increased gut homing T-cells. The d-MAM profiles suggest species and strain-based variations between the two FGID subtypes and in comparison to controls.
Topics: Humans; Wheat Hypersensitivity; Self Report; Gastrointestinal Microbiome; Gastrointestinal Diseases; Intestinal Mucosa; Sensation
PubMed: 36303431
DOI: 10.1080/19490976.2022.2132078 -
Frontiers in Microbiology 2022Microgravity influences are prevalent during orbital flight and can adversely affect astronaut physiology. Notably, it may affect the physicochemical properties of...
Microgravity influences are prevalent during orbital flight and can adversely affect astronaut physiology. Notably, it may affect the physicochemical properties of saliva and the salivary microbial community. Therefore, this study simulates microgravity in space using a ground-based -6° head-down bed rest (HDBR) test to observe the effects of microgravity on oral salivary secretion function and the salivary microbiome. Sixteen healthy young male volunteers were recruited for the 15-day -6° HDBR test. Non-stimulated whole saliva was collected on day 1 (pre-HDBR), on days 5, 10, and 15 of HDBR, and day 6 of recovery. Salivary pH and salivary flow rate were measured, and the V3-V4 region of the 16S rRNA gene was sequenced and analyzed in 80 saliva samples. The results showed that there were no significant differences in salivary pH, salivary flow rate, and alpha diversity between any two time points. However, beta diversity analysis revealed significant differences between pre-HDBR and the other four time points. After HDBR, the relative abundances of , , , , , and increased significantly, whereas the relative abundances of and decreased significantly. However, the relative abundances of and did not recover to the pre-HDBR level on day 6 of recovery. Network analysis revealed that the number of relationships between genera decreased, and the positive and negative correlations between genera changed in a complex manner after HDBR and did not reach their original levels on day 6 of recovery. PICRUSt analysis demonstrated that some gene functions of the salivary microbiome also changed after HDBR and remained significantly different from those before HDBR on day 6 of recovery. Collectively, 15 days of -6° HDBR had minimal effect on salivary secretion function but resulted in significant changes in the salivary microbiome, mainly manifested as an increase in oral disease-related bacteria and a decrease in oral health-related commensal bacteria. Further research is required to confirm these oral microbial changes and explore the underlying pathological mechanisms to determine the long-term effects on astronauts embarking on long-duration voyages to outer space.
PubMed: 36439790
DOI: 10.3389/fmicb.2022.1056637 -
Nature Medicine May 2024Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises...
Despite substantial progress in cancer microbiome research, recognized confounders and advances in absolute microbiome quantification remain underused; this raises concerns regarding potential spurious associations. Here we study the fecal microbiota of 589 patients at different colorectal cancer (CRC) stages and compare observations with up to 15 published studies (4,439 patients and controls total). Using quantitative microbiome profiling based on 16S ribosomal RNA amplicon sequencing, combined with rigorous confounder control, we identified transit time, fecal calprotectin (intestinal inflammation) and body mass index as primary microbial covariates, superseding variance explained by CRC diagnostic groups. Well-established microbiome CRC targets, such as Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for these covariates. In contrast, the associations of Anaerococcus vaginalis, Dialister pneumosintes, Parvimonas micra, Peptostreptococcus anaerobius, Porphyromonas asaccharolytica and Prevotella intermedia remained robust, highlighting their future target potential. Finally, control individuals (age 22-80 years, mean 57.7 years, standard deviation 11.3) meeting criteria for colonoscopy (for example, through a positive fecal immunochemical test) but without colonic lesions are enriched for the dysbiotic Bacteroides2 enterotype, emphasizing uncertainties in defining healthy controls in cancer microbiome research. Together, these results indicate the importance of quantitative microbiome profiling and covariate control for biomarker identification in CRC microbiome studies.
Topics: Humans; Colorectal Neoplasms; Middle Aged; Feces; Female; Aged; Male; RNA, Ribosomal, 16S; Adult; Gastrointestinal Microbiome; Aged, 80 and over; Young Adult; Microbiota; Leukocyte L1 Antigen Complex
PubMed: 38689063
DOI: 10.1038/s41591-024-02963-2 -
Journal of Prosthodontics : Official... Apr 2024To characterize the microbiome composition in peri-implant pocket of peri-implantitis and peri-implant sulcus controls using 16S rRNA gene sequencing.
PURPOSE
To characterize the microbiome composition in peri-implant pocket of peri-implantitis and peri-implant sulcus controls using 16S rRNA gene sequencing.
MATERIALS AND METHODS
In this controlled clinical cross-sectional study, 23 subjects with control implants (n = 14) and diseased implants (peri-implantitis, n = 21) were included. The peri-implant pocket/sulcus was sampled and used to extract DNA and amplify the 16S rRNA gene using universal primers targeting the V3-V4 regions. The resulting 16S PCR amplicons were sequenced on Illumina MiSeq, and the sequences were processed using DADA2 and the Human Oral Microbiome Database (HOMD) as references. Alpha and Beta diversity, as well as core microbiome and differential abundance analyses, were performed using the MicrobiomeAnalyst workflow.
RESULTS
There were no significant differences in microbial diversity between control implants and implants with peri-implantitis (Shannon p = 0.82). Overall bacterial community structure assessed through beta diversity analysis was also not significantly different between the two groups (p = 0.18). However, high levels of Gram-negative bacteria were detected in peri-implant pockets compared to the control sulcus. Abundant species in peri-implantitis were Capnocytophaga leadbetteri, Treponema maltophilum, Peptostreptococcus, Neisseria, P. gingivalis, and Porphyromonas endodontali, Lactococcus lactis and Filifactor alocis (p < 0.05). Gram-positive bacteria such as Streptococcus salivaris, Prevotella melaninogenica, L. wadei, and Actinomyces spp. serve were more abundant in peri-implant control sulcus.
CONCLUSIONS
Peri-implant sulcus in control implants harbors predominantly Gram-positive bacteria, whereas pockets of implants with peri-implantitis harbor predominantly Gram-negative bacteria.
Topics: Humans; Peri-Implantitis; Dental Implants; RNA, Ribosomal, 16S; Cross-Sectional Studies; Microbiota
PubMed: 37527556
DOI: 10.1111/jopr.13743 -
Food & Function Aug 2023Oral microbial dysbiosis is the primary etiologic factor for halitosis and may be the critical preventive target for halitosis. This study included randomized controlled... (Randomized Controlled Trial)
Randomized Controlled Trial
Oral microbial dysbiosis is the primary etiologic factor for halitosis and may be the critical preventive target for halitosis. This study included randomized controlled trials (RCTs) assessing the effects of ET-22 live and heat-killed bacteria on halitosis and the related oral microbiome. 68 halitosis subjects were divided into placebo, ET-22 live (ET-22.L) and ET-22 heat-killed (ET-22.HK) groups. Subjects took different lozenges three times a day for 4 weeks and underwent saliva collection and assessment of breath volatile sulfur compound (VSC) levels at the beginning and end of the intervention. Salivary volatile organic compounds were measured using HS-SPME-GC/MS, and the microbiome profile was determined by 16S rRNA gene amplicon sequencing. A positive decrease in breath volatile sulfur compound (VSC) levels was observed in the means of both ET-22.L and ET-22.HK groups after 4 weeks of intervention, being more marked in the ET-22.L group ( = 0.0148). Moreover, ET-22.L and ET-22.HK intervention remarkably changed the composition of total salivary volatile organic compounds (VOCs) and aroma-active VOCs. Key undesirable VOCs, such as indole, pyridine, nonanoic acid, benzothiazole, and valeric acid, were significantly reduced. Meanwhile, ET-22.L or ET-22.HK also altered the taxonomic composition of the salivary microbiome. The halitosis pathogens and were significantly reduced in the ET-22.HK group and the pathogenic and were significantly inhibited in the ET-22.L group. Collectively, our study suggests that both ET-22.L and ET-22.HK can significantly inhibit the production of undesirable odor compounds in subjects with halitosis, which may be related to the changes of the oral microbiome.
Topics: Humans; Double-Blind Method; Halitosis; Lacticaseibacillus paracasei; Microbiota; Randomized Controlled Trials as Topic; Sulfur; Sulfur Compounds; Volatile Organic Compounds
PubMed: 37493204
DOI: 10.1039/d3fo02271d