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Frontiers in Immunology 2023Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are...
BACKGROUND
Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.
METHODS
Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer.
RESULTS
60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. (p=0.028), (p=0.0295) (p=0.034) (p=0.029) were enriched in anal cancer specimens when compared to HR normal.
CONCLUSION
Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal , , and abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.
Topics: Humans; Female; Papillomavirus Infections; Prospective Studies; Cross-Sectional Studies; Anus Neoplasms; Carcinoma, Squamous Cell; Microbiota; Tumor Microenvironment
PubMed: 37063829
DOI: 10.3389/fimmu.2023.1051431 -
Anaerobe Oct 2022Anaerobic cocci are common anaerobic isolates. Numerous genera of anaerobic cocci have been reported in both urinary tract microbiota, mainly of females, and in cases of... (Review)
Review
Anaerobic cocci are common anaerobic isolates. Numerous genera of anaerobic cocci have been reported in both urinary tract microbiota, mainly of females, and in cases of urinary tract infections (UTIs), predominantly in patients with comorbidities, when no facultatively anaerobic bacteria were detected from the urine samples. UTIs caused by anaerobic cocci have been reported in >7% in some studies. As the routine diagnostic methods may be insufficient to detect and identify the anaerobic cocci in patients with UTIs, enhanced quantitative urine culture (EQUC) can give better results. EQUC is performed by plating urine samples onto different media to be incubated in both aerobic and anaerobic conditions with a prolonged incubation time. Other newer methods such as 16S rRNA gene sequencing, qualitative PCR and Next Generation Sequencing can also be considered. Anaerobic cocci such as Peptoniphilus, Parvimonas, Anaerococcus and Finegoldia spp. were found in patients with bacteremia of urinary source. A fatal outcome has been reported in a diabetic patient with emphysematous pyelonephritis caused by Finegoldia magna and Candida parapsilosis due to a delay in seeking hospital care during the COVID-19 pandemic. In specific cases such as of chronic infections, immunosuppression, comorbidity, advanced age, following urological tract manipulations and negative culture results for usual uropathogens, it may be advisable to use suprapubic aspiration cultured in both aerobic and anaerobic condition or EQUC using media which support the relative slow growing anaerobic cocci as well.
Topics: Female; Humans; Bacteria, Anaerobic; RNA, Ribosomal, 16S; Anaerobiosis; Pandemics; COVID-19; Urinary Tract Infections
PubMed: 34990817
DOI: 10.1016/j.anaerobe.2021.102509 -
Frontiers in Immunology 2023The intricate connection between gut microbiota and rheumatoid arthritis (RA) pathogenesis has gained prominence, although the specific microbial species contributing to...
INTRODUCTION
The intricate connection between gut microbiota and rheumatoid arthritis (RA) pathogenesis has gained prominence, although the specific microbial species contributing to RA development remain largely unknown. Recent studies have sought to comprehensively explore alterations in the human microbiome, focusing on identifying disease-related microbial species through blood analysis. Consequently, this study aimed to identify RA-associated microbial species using a serum microbial array system and to investigate the efficacy and underlying mechanisms of potential microbial species for RA treatment.
METHODS
Serum immunoglobulin M levels against 384 intestinal microbial species were assessed using a microbial microarray in patients with RA and healthy individuals. We investigated the therapeutic potential of the identified microbial candidate regarding arthritis development, immune responses, gut barrier function, and gut microbiome using a collagen-induced arthritis (CIA) mouse model.
RESULTS
Our findings revealed significant alterations in antibody levels against 36 microbial species in patients with RA compared to healthy individuals. Notably, the antibody levels against () were decreased in patients with RA and exhibited an inverse correlation with RA disease activity. experiments demonstrated that produced acetate and butyrate, while exhibiting anti-inflammatory properties. In CIA mice, administration suppressed arthritis symptoms, reduced the accumulation of inflammatory monocytes in the mesenteric lymph nodes, and downregulated gene expression of pro-inflammatory cytokines in the ileum. Additionally, supplementation restored intestinal barrier integrity and partially resolved gut microbial dysbiosis in CIA mice. The fecal microbiota in -treated mice corresponded to improved intestinal barrier integrity and reduced inflammatory responses.
CONCLUSION
This study highlights the potential of serum-based detection of anti-microbial antibodies to identify microbial targets at the species level for RA treatment. Moreover, our findings suggest that , identified through the microbial microarray analysis, holds therapeutic potential for RA by restoring intestinal barrier integrity and suppressing the immunologic response associated with RA.
Topics: Mice; Humans; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Disease Models, Animal; Cytokines; Firmicutes
PubMed: 38239365
DOI: 10.3389/fimmu.2023.1286387 -
Dermatology (Basel, Switzerland) 2024Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection...
INTRODUCTION
Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity.
METHODS
All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing.
RESULTS
Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively.
CONCLUSION
Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.
Topics: Humans; Darier Disease; Male; Female; Dysbiosis; Adult; Middle Aged; Microbiota; Axilla; Skin; Corynebacterium; Young Adult; Propionibacterium; Micrococcus; Severity of Illness Index; Hand; Thorax; Scalp; Aged; Adolescent
PubMed: 38330926
DOI: 10.1159/000537714 -
Nutrients Nov 2022This study aimed to investigate the relationship between anxiety, depression, and gut microbiota in elderly patients with FC.
UNLABELLED
This study aimed to investigate the relationship between anxiety, depression, and gut microbiota in elderly patients with FC.
METHODS
in this cross-sectional study, a total of 198 elderly participants (85 male and 113 female) aged over 60 years were recruited. The study was conducted in Changsha city, China. The participants completed an online questionnaire, including The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), The Patient Assessment of Symptoms (PAC-SYM), and The Patient Assessment of Quality of Life (PAC-QoL). We selected the 16S rDNA V3 + V4 region as the amplification region and sequenced the gut microbiota using the Illumina Novaseq PE250 high-throughput sequencing platform.
RESULTS
in total, 30.3% of patients with constipation had depression, while 21.3% had anxiety. The relative abundance of intestinal microbiota in the normal group was higher than that in the anxiety and depression group. According to LEfSe analysis, the relative abundance of and in the people without depression and anxiety was higher. The relative abundance of and in the depression group was lower, and the relative abundance of and in the anxiety group was higher. In addition, according to the correlation analysis, and were negatively correlated with constipation symptoms, anxiety, and depression.
CONCLUSIONS
this study found that gut microbiota composition may be associated with a higher incidence of anxiety and depression in patients with FC, thus providing insight into the mechanisms that ameliorate mood disorders in patients with FC.
Topics: Aged; Humans; Male; Female; Middle Aged; Gastrointestinal Microbiome; Quality of Life; Cross-Sectional Studies; East Asian People; Anxiety; Constipation; Clostridiales; Depression
PubMed: 36501044
DOI: 10.3390/nu14235013 -
Investigative and Clinical Urology Sep 2022Recent advances in molecular biology technology have allowed identification of microbial communities in the urinary tract, and urinary microbiome is associated with...
PURPOSE
Recent advances in molecular biology technology have allowed identification of microbial communities in the urinary tract, and urinary microbiome is associated with various urological diseases. In this study, we aimed to characterize the urinary microbiome of genitourinary malignancies.
MATERIALS AND METHODS
Metagenomic analysis of urinary DNA was performed in 85 patients including 30 with bladder cancer (BC), 27 with prostate cancer (PC), 12 with renal cancer (RC), and 16 with non-cancer (NC). 16S rRNA gene sequencing was conducted after amplification of the V3-V4 region.
RESULTS
PC and RC had significantly lower Shannon index than BC, and beta diversity showed significantly different microbiome composition between four groups. We identified six genera of , , , , , and , which showed significantly different abundance between the four groups. When each of the malignancies were compared to NC at the species level, sp. was significantly increased in BC. We also identified 12 and five species with increased populations in PC and RC, respectively. Of these, , , , and were significantly increased in both PC and RC.
CONCLUSIONS
Urinary microbiome composition was different depending on the type of genitourinary malignancies, and we identified bacteria that are significantly associated with each type of malignancy. Specifically, several bacterial species were associated both PC and RC, suggesting that PC and RC share a similar pathogenesis-related urinary microbiome.
Topics: Bacteria; Humans; Male; Microbiota; Prostatic Neoplasms; RNA, Ribosomal, 16S; Urinary Bladder Neoplasms; Urinary Tract
PubMed: 36068003
DOI: 10.4111/icu.20220124 -
Microbiology Spectrum Dec 2022The knowledge of bacterial species diversity within the female urinary microbiome (FUM) is essential for understanding the role of the FUM in urinary tract health and...
The knowledge of bacterial species diversity within the female urinary microbiome (FUM) is essential for understanding the role of the FUM in urinary tract health and disease. This study aimed to characterize the bacterial species diversity of the FUM of asymptomatic reproductive-age European women by combining extended culturomics and long-read sequencing of the near-full-length 16S rRNA gene. A total of 297 bacterial species (median of 53 species/sample) were identified, yet only 22% of the species were detected by both culture and sequencing methods. Recently recognized , , and species and 5 new putative species were identified by culturomics, while anaerobic species (e.g., 11 spp.) were mostly detected by amplicon sequencing. Notably, there was not a single species common to all samples, although members of the genus were detected in all. Lactobacillus crispatus, Lactobacillus iners, and Lactobacillus mulieris were observed in high relative abundance in several samples, as well as other species (e.g., Streptococcus agalactiae, Fannyhessea vaginae, Gardnerella vaginalis, Gardnerella swidsinskii), while low-abundance members (e.g., Finegoldia magna) were often more prevalent. A moderate correlation (Mantel test; = 0.5) between community structure types captured by culturomics and amplicon sequencing was observed, highlighting the benefit of combining both methodologies. This study provided a detailed FUM structure at the species level, which is critical to unveil the potential relationship between specific microbiome members and urinary diseases/disorders. Moreover, the different capacity to characterize microbiome profiles of culturomic and amplicon sequencing is described, providing valuable insights for further urinary microbiome studies. The bacterial species diversity within the female urinary microbiome (FUM) has been insufficiently characterized. This study demonstrated that complementarity between optimized culture-dependent and -independent approaches is highly beneficial for comprehensive FUM species profiling by detecting higher FUM species diversity than previously reported, including identification of unreported species belonging to the genera , , and and putative novel species. Although some species were present in high relative abundance, low-abundance members were more prevalent. FUM classification into community structure types demonstrated high interindividual differences in urinary microbiome composition among asymptomatic women. We also report moderate correlation between culture-dependent and -independent derived data-highlighting drawbacks of each methodological approach. Our findings suggest that FUM bacterial diversity reported from previous studies may be underestimated. Finally, our results contribute to the fundamental knowledge of the FUM required for further exploration of the urinary microbiome role in urinary tract diseases.
Topics: Humans; Female; RNA, Ribosomal, 16S; Urinary Tract; Gardnerella vaginalis; Bacteria; Corynebacterium; Microbiota; European People; Vagina
PubMed: 36383025
DOI: 10.1128/spectrum.01308-22 -
Frontiers in Cellular and Infection... 2022Age-related changes in nasal bacterial microbiota of patients with chronic rhinosinusitis (CRS) remains unclear. In this study, we aimed to identify distinct...
Age-related changes in nasal bacterial microbiota of patients with chronic rhinosinusitis (CRS) remains unclear. In this study, we aimed to identify distinct characteristics of nasal bacterial microbiota between aged and younger patients with CRS through 16S rDNA gene sequencing. Patients with CRS undergoing endoscopic sinus surgery were recruited and separated into aged (≥60 years, median age = 66 years, N = 17) and younger (<60 years, median age = 35.5 years, N = 14) patients. Diversity, bacterial composition and metabolic activities of nasal microbiota between aged and younger patients were compared. Results have shown that levels of OTUs (p = 0.0173) and microbiota diversity (all p < 0.05) decreased significantly in aged patients. The abundance of phylum , and genus were significantly higher in aged patients, while the abundance of phylum , , and genus , were significantly higher in younger patients. In addition, predicted functional profiles have revealed that 41 KEGG pathways involving in 12 metabolic pathways, 4 genetic information processing, 3 environmental information processing, 4 cellular processes, 8 organismal systems, 6 human diseases, and 4 unclassified pathways were identified. Among which, the vast majority of metabolic activities are involved in replication and repair, membrane transport, translation, and the metabolism of amino acid, carbohydrate, energy, cofactors and vitamins, and nucleotide. On the level of the thirdly bacterial metabolic pathways, purine metabolism, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, glycolysis/gluconeogenesis and phenylalanine, tyrosine and tryptophan biosynthesis are significantly up-regulated while carbon fixation pathways in prokaryotesand methane metabolism are significantly down-regulated in aged patients. Overall, our analysis revealed that age-related physiological and pathological changes on the nasal mucosal surface may alter the host immune response and be highly associated with the nasal bacterial microbiota of patients with CRS. However, future studies are needed to elucidate the causal relationship.
Topics: Adult; Aged; Chronic Disease; Humans; Microbiota; Middle Aged; Nasal Mucosa; RNA, Ribosomal, 16S; Rhinitis; Sinusitis
PubMed: 35252024
DOI: 10.3389/fcimb.2022.786481 -
Journal of Gastroenterology Mar 2024Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and...
BACKGROUND
Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC.
METHODS
The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes.
RESULTS
The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO.
CONCLUSIONS
Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.
Topics: Humans; RNA, Ribosomal, 16S; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Prognosis; Microbiota
PubMed: 38242997
DOI: 10.1007/s00535-023-02069-5 -
Microbiology Spectrum Feb 2022Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD), with a substantially negative impact on patient management and...
Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD), with a substantially negative impact on patient management and outcome. The development and progression of CI exhibits high interindividual variability, which requires better diagnostic and monitoring strategies. PD patients often display sweating disorders resulting from autonomic dysfunction, which has been associated with CI. Because the axillary microbiota is known to change with humidity level and sweat composition, we hypothesized that the axillary microbiota of PD patients shifts in association with CI progression, and thus can be used as a proxy for classification of CI stages in PD. We compared the axillary microbiota compositions of 103 PD patients (55 PD patients with dementia [PDD] and 48 PD patients with mild cognitive impairment [PD-MCI]) and 26 cognitively normal healthy controls (HC). We found that axillary microbiota profiles differentiate HC, PD-MCI, and PDD groups based on differential ranking analysis, and detected an increasing trend in the log ratio of to in progression from HC to PDD. In addition, phylogenetic factorization revealed that the depletion of the , and genera is associated with PD-MCI and PDD. Moreover, functional predictions suggested significant increases in myo-inositol degradation, ergothioneine biosynthesis, propionate biosynthesis, menaquinone biosynthesis, and the proportion of aerobic bacteria and biofilm formation capacity, in parallel to increasing CI. Our results suggest that alterations in axillary microbiota are associated with CI in PD. Thus, axillary microbiota has the potential to be exploited as a noninvasive tool in the development of novel strategies. Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment (CI) in PD has significant negative impacts on life quality of patients. The emergence and progression of cognitive impairment shows high variability among PD patients, and thus requires better diagnostic and monitoring strategies. Recent findings indicate a close link between autonomic dysfunction and cognitive impairment. Since thermoregulatory dysfunction and skin changes are among the main manifestations of autonomic dysfunction in PD, we hypothesized that alterations in the axillary microbiota may be useful for tracking cognitive impairment stages in PD. To our knowledge, this the first study characterizing the axillary microbiota of PD patients and exploring its association with cognitive impairment stages in PD. Future studies should include larger cohorts and multicenter studies to validate our results and investigate potential biological mechanisms.
Topics: Aged; Axilla; Bacteria; Cognitive Dysfunction; Female; Humans; Male; Microbiota; Middle Aged; Parkinson Disease; Phylogeny
PubMed: 35138147
DOI: 10.1128/spectrum.02358-21