-
Gastroenterology Dec 2023Pien Tze Huang (PZH) is a well-established traditional medicine with beneficial effects against inflammation and cancer. We aimed to explore the chemopreventive effect...
BACKGROUND & AIMS
Pien Tze Huang (PZH) is a well-established traditional medicine with beneficial effects against inflammation and cancer. We aimed to explore the chemopreventive effect of PZH in colorectal cancer (CRC) through modulating gut microbiota.
METHODS
CRC mouse models were established by azoxymethane plus dextran sulfate sodium treatment or in Apc mice treated with or without PZH (270 mg/kg and 540 mg/kg). Gut barrier function was determined by means of intestinal permeability assays and transmission electron microscopy. Fecal microbiota and metabolites were analyzed by means of metagenomic sequencing and liquid chromatography mass spectrometry, respectively. Germ-free mice or antibiotic-treated mice were used as models of microbiota depletion.
RESULTS
PZH inhibited colorectal tumorigenesis in azoxymethane plus dextran sulfate sodium-treated mice and in Apc mice in a dose-dependent manner. PZH treatment altered the gut microbiota profile, with an increased abundance of probiotics Pseudobutyrivibrio xylanivorans and Eubacterium limosum, while pathogenic bacteria Aeromonas veronii, Campylobacter jejuni, Collinsella aerofaciens, and Peptoniphilus harei were depleted. In addition, PZH increased beneficial metabolites taurine and hypotaurine, bile acids, and unsaturated fatty acids, and significantly restored gut barrier function. Transcriptomic profiling revealed that PZH inhibited PI3K-Akt, interleukin-17, tumor necrosis factor, and cytokine-chemokine signaling. Notably, the chemopreventive effect of PZH involved both microbiota-dependent and -independent mechanisms. Fecal microbiota transplantation from PZH-treated mice to germ-free mice partly recapitulated the chemopreventive effects of PZH. PZH components ginsenoside-F2 and ginsenoside-Re demonstrated inhibitory effects on CRC cells and primary organoids, and PZH also inhibited tumorigenesis in azoxymethane plus dextran sulfate sodium-treated germ-free mice.
CONCLUSIONS
PZH manipulated gut microbiota and metabolites toward a more favorable profile, improved gut barrier function, and suppressed oncogenic and pro-inflammatory pathways, thereby suppressing colorectal carcinogenesis.
Topics: Mice; Animals; Signal Transduction; Gastrointestinal Microbiome; Dextran Sulfate; Phosphatidylinositol 3-Kinases; Apoptosis; Medicine, Traditional; Colorectal Neoplasms; Carcinogenesis; Azoxymethane
PubMed: 37704113
DOI: 10.1053/j.gastro.2023.08.052 -
Genome Medicine Nov 2016Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators...
BACKGROUND
Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer.
METHODS
We undertook a study of the microbiome in samples taken from different locations along the female reproductive tract in patients with endometrial cancer (n = 17), patients with endometrial hyperplasia (endometrial cancer precursor, n = 4), and patients afflicted with benign uterine conditions (n = 10). Vaginal, cervical, Fallopian, ovarian, peritoneal, and urine samples were collected aseptically both in the operating room and the pathology laboratory. DNA extraction was followed by amplification and high-throughput next generation sequencing (MiSeq) of the 16S rDNA V3-V5 region to identify the microbiota present. Microbiota data were summarized using both α-diversity to reflect species richness and evenness within bacterial populations and β-diversity to reflect the shared diversity between bacterial populations. Statistical significance was determined through the use of multiple testing, including the generalized mixed-effects model.
RESULTS
The microbiome sequencing (16S rDNA V3-V5 region) revealed that the microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries) are significantly correlated (p < 0.001) and that there is a structural microbiome shift in the cancer and hyperplasia cases, distinguishable from the benign cases (p = 0.01). Several taxa were found to be significantly enriched in samples belonging to the endometrial cancer cohort: Firmicutes (Anaerostipes, ph2, Dialister, Peptoniphilus, 1-68, Ruminococcus, and Anaerotruncus), Spirochaetes (Treponema), Actinobacteria (Atopobium), Bacteroidetes (Bacteroides and Porphyromonas), and Proteobacteria (Arthrospira). Of particular relevance, the simultaneous presence of Atopobium vaginae and an uncultured representative of the Porphyromonas sp. (99 % match to P. somerae) were found to be associated with disease status, especially if combined with a high vaginal pH (>4.5).
CONCLUSIONS
Our results suggest that the detection of A. vaginae and the identified Porphyromonas sp. in the gynecologic tract combined with a high vaginal pH is statistically associated with the presence of endometrial cancer. Given the documented association of the identified microorganisms with other pathologies, these findings raise the possibility of a microbiome role in the manifestation, etiology, or progression of endometrial cancer that should be further investigated.
Topics: Adult; Aged; Bacteria; DNA, Bacterial; DNA, Ribosomal; Endometrial Hyperplasia; Endometrial Neoplasms; Fallopian Tubes; Female; Humans; Middle Aged; Ovary; Phylogeny; RNA, Ribosomal, 16S; Risk Factors; Sequence Analysis, DNA; Urine; Uterus; Vagina
PubMed: 27884207
DOI: 10.1186/s13073-016-0368-y -
Archives of Microbiology Jul 2022Strains Marseille-P3761 and Marseille-P3195 are representatives of two bacterial species isolated from human specimens. Strain Marseille-P3761 was isolated from the...
Strains Marseille-P3761 and Marseille-P3195 are representatives of two bacterial species isolated from human specimens. Strain Marseille-P3761 was isolated from the stool of a healthy volunteer, while strain Marseille-P3915 was cultivated from the urine of a kidney transplant recipient. Both strains are anaerobic Gram-positive coccoid bacteria. Both are catalase-negative and oxidase-negative and grow optimally at 37 °C in anaerobic conditions. They also metabolize carbohydrates, such as galactose, glucose, fructose, and glycerol. The major fatty acids were hexadecanoic acid for both strains. The highest digital DNA-DNA hybridization (dDDH) values of Marseille-P3761 and Marseille-P3195 strains when compared to their closest phylogenetic relatives were 52.3% and 56.4%, respectively. Strains Marseille-P3761 and Marseille-P3195 shared an OrthoANI value of 83.5% which was the highest value found with Peptoniphilus species studied here. The morphological, biochemical, phenotypic and genomic characteristics strongly support that these strains are new members of the Peptoniphilus genus. Thus, we suggest that Peptoniphilus coli sp. nov., and Peptoniphilus urinae sp. nov., are new species for which strains Marseille-P3761 (CSUR P3761 = CCUG 71,569) and Marseille-P3195 (CSUR P3195 = DSM 103,468) are their type strains, respectively of two new Peptoniphilus species, for which we propose the names Peptoniphilus coli sp. nov. and Peptoniphilus urinae sp. nov., respectively.
Topics: Bacteria, Anaerobic; Bacterial Typing Techniques; Clostridiales; DNA, Bacterial; Fatty Acids; Gram-Positive Bacteria; Humans; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 35857142
DOI: 10.1007/s00203-022-03044-z -
International Journal of Molecular... Sep 2022Recently, interest in the microbiome of cutaneous diseases has increased tremendously. Of particular interest is the gut-brain-skin axis proposed by Stokes and Pillsbury... (Review)
Review
Recently, interest in the microbiome of cutaneous diseases has increased tremendously. Of particular interest is the gut-brain-skin axis proposed by Stokes and Pillsbury in 1930. The microbiome has been suggested in the pathogenesis of hidradenitis suppurativa, however the link between the commensals and the host is yet to be established. Across all studies, the increased abundance of , and spp., and a loss of skin commensal species, such as in HS lesions, is a consistent finding. The role of gut and blood microbiome in hidradenitis suppurativa has not been fully elucidated. According to studies, the main link with the intestine is based on the increased risk of developing Crohn's disease and ulcerative colitis, however, further research is highly needed in this area. Lifestyle, dietary approaches, and probiotics all seem to influence the microbiome, hence being a promising modality as adjuvant therapy. The aim of this review was to present the latest reports in the field of research on skin, blood, and gut microbiome in terms of hidradenitis suppurativa.
Topics: Crohn Disease; Gastrointestinal Microbiome; Hidradenitis Suppurativa; Humans; Microbiota; Skin
PubMed: 36232581
DOI: 10.3390/ijms231911280 -
Frontiers in Immunology 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gut luminal cells through the angiotensin-converting enzyme-2 receptor and disrupts the gut...
OBJECTIVES
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gut luminal cells through the angiotensin-converting enzyme-2 receptor and disrupts the gut microbiome. We investigated whether the gut microbiome in the early stage of SARS-CoV-2 infection was associated with the prognosis of coronavirus disease (COVID-19).
METHODS
Thirty COVID-19 patients and 16 healthy controls were prospectively enrolled. Blood and stool samples and clinical details were collected on days 0 (enrollment), 7, 14, and 28. Participants were categorized into four groups by their clinical course.
RESULTS
Gut microbiota composition varied during the clinical course of COVID-19 and was closely associated with cytokine levels (=0.003). A high abundance of the genus (linear discriminant analysis [LDA] effect size: 3.97856, =0.004), species (LDA effect size: 4.00551, =0.020), and (LDA effect size: 4.00885, =0.007) was associated with a good prognosis. Starch, sucrose, and galactose metabolism was highly activated in the gut microbiota of the poor prognosis group. Glucose-lowering diets, including whole grains, were positively correlated with a good prognosis.
CONCLUSION
Gut microbiota may mediate the prognosis of COVID-19 by regulating cytokine responses and controlling glucose metabolism, which is implicated in the host immune response to SARS-CoV-2.
Topics: Humans; COVID-19; Gastrointestinal Microbiome; SARS-CoV-2; Cytokines; Prognosis; Disease Progression
PubMed: 37051240
DOI: 10.3389/fimmu.2023.1079277 -
European Urology Oncology Aug 2022Bacteria play a suspected role in the development of several cancer types, and associations between the presence of particular bacteria and prostate cancer have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bacteria play a suspected role in the development of several cancer types, and associations between the presence of particular bacteria and prostate cancer have been reported.
OBJECTIVE
To provide improved characterisation of the prostate and urine microbiome and to investigate the prognostic potential of the bacteria present.
DESIGN, SETTING, AND PARTICIPANTS
Microbiome profiles were interrogated in sample collections of patient urine (sediment microscopy: n = 318, 16S ribosomal amplicon sequencing: n = 46; and extracellular vesicle RNA-seq: n = 40) and cancer tissue (n = 204).
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Microbiomes were assessed using anaerobic culture, population-level 16S analysis, RNA-seq, and whole genome DNA sequencing.
RESULTS AND LIMITATIONS
We demonstrate an association between the presence of bacteria in urine sediments and higher D'Amico risk prostate cancer (discovery, n = 215 patients, p < 0.001; validation, n = 103, p < 0.001, χ test for trend). Characterisation of the bacterial community led to the (1) identification of four novel bacteria (Porphyromonas sp. nov., Varibaculum sp. nov., Peptoniphilus sp. nov., and Fenollaria sp. nov.) that were frequently found in patient urine, and (2) definition of a patient subgroup associated with metastasis development (p = 0.015, log-rank test). The presence of five specific anaerobic genera, which includes three of the novel isolates, was associated with cancer risk group, in urine sediment (p = 0.045, log-rank test), urine extracellular vesicles (p = 0.039), and cancer tissue (p = 0.035), with a meta-analysis hazard ratio for disease progression of 2.60 (95% confidence interval: 1.39-4.85; p = 0.003; Cox regression). A limitation is that functional links to cancer development are not yet established.
CONCLUSIONS
This study characterises prostate and urine microbiomes, and indicates that specific anaerobic bacteria genera have prognostic potential.
PATIENT SUMMARY
In this study, we investigated the presence of bacteria in patient urine and the prostate. We identified four novel bacteria and suggest a potential prognostic utility for the microbiome in prostate cancer.
Topics: Bacteria; Humans; Male; Microbiota; Prostate; Prostatic Neoplasms; RNA, Ribosomal, 16S
PubMed: 35450835
DOI: 10.1016/j.euo.2022.03.006 -
Frontiers in Cellular and Infection... 2022A 39-year-old woman with a 3-year human papillomavirus (HPV) 18 infection history was admitted to the hospital for a 16-day history of vaginal bleeding after sex. She...
A 39-year-old woman with a 3-year human papillomavirus (HPV) 18 infection history was admitted to the hospital for a 16-day history of vaginal bleeding after sex. She was diagnosed with cervical cancer based on the results of the electronic colposcopy, cervical cytology, microscopy, and magnetic resonance imaging (MRI). Then, she received chemotherapy, with paclitaxel 200 mg (day 1), cisplatin 75 mg (day 2), and bevacizumab 700 mg (day 3) twice with an interval of 27 days. During the examination for the diagnosis and treatment, many invasive operations, including removal of intrauterine device, colposcopy, and ureteral dilatation, were done. After that, the patient was discharged and entered the emergency department about 2.5 months later with a loss of consciousness probably caused by septic shock. The patient finally died of multiple organ failure and bacterial infection, although she has received antimicrobial therapy. The blood cultures showed a monobacterial infection with an anaerobic Gram-positive bacterial strain, designated as SAHP1. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) indicated that the patient was infected with , while molecular analysis and genome-based taxonomy confirmed the infection with a novel species that has a close genetic relationship with and proposed provisionally as sp. nov., which may also act as a commensal of the human vagina. Genomic features of SAHP1 have been fully described, and comparative genomic analysis reveals the known prokaryote relative of sp. nov. in the genus The invasive operations on the genital tract during the diagnosis and treatment of the patient and the tumor tissue damage and bleeding may have a certain role in the bloodstream infection. This study casts a new light on the bacteria and prompts clinicians to include anaerobic blood cultures as part of their blood culture procedures, especially on patients with genital tract tumors. Furthermore, due to the incomplete database and unsatisfying resolution of the MALDI-TOF MS for species identification, molecular identification, especially whole-genome sequencing, is required for those initially identified as bacteria belonging to in the clinical laboratory.
Topics: Adult; Bacteria; Blood Culture; Clostridiales; Female; Firmicutes; Gram-Positive Bacteria; Humans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Uterine Cervical Neoplasms
PubMed: 35880078
DOI: 10.3389/fcimb.2022.954355 -
Archives of Microbiology Sep 2022
PubMed: 36166171
DOI: 10.1007/s00203-022-03248-3 -
MicrobiologyOpen Mar 2019Three previously unidentified Gram-positive anaerobic coccoid bacteria, strains KhD-2 , KHD4 , and Kh-D5 , isolated from a vaginal swab, were characterized using the...
Description of three new Peptoniphilus species cultured in the vaginal fluid of a woman diagnosed with bacterial vaginosis: Peptoniphilus pacaensis sp. nov., Peptoniphilus raoultii sp. nov., and Peptoniphilus vaginalis sp. nov.
Three previously unidentified Gram-positive anaerobic coccoid bacteria, strains KhD-2 , KHD4 , and Kh-D5 , isolated from a vaginal swab, were characterized using the taxonogenomics concept. The phylogenic analysis, phenotypic characteristics, and genotypic data presented in this report attest that these three bacteria are distinct from previously known bacterial species with standing in nomenclature and represent three new Peptoniphilus species. Strain KhD-2 is most closely related to Peptoniphilus sp. DNF00840 and Peptoniphilus harei (99.7% and 98.2% identity, respectively); strain KHD4 to Peptoniphilus lacrimalis (96%) and strain Kh-D5 to Peptoniphilus coxii (97.2%). Strains KhD-2 , KHD4 , and Kh-D5 DNA G+C contents are, respectively, 34.23%, 31.87%, and 49.38%; their major fatty acid was C (41.6%, 32.0%, and 36.4%, respectively). We propose that strains KhD-2 (=CSUR P0125 = DSM 101742), KHD4 (=CSUR P0110 = CECT 9308), and Kh-D5 (=CSUR P2271 = DSM 101839) be the type strains of the new species for which the names Peptoniphilus vaginalis sp. nov., Peptoniphilus raoultii sp. nov., and Peptoniphilu pacaensis sp. nov., are proposed, respectively.
Topics: Adult; Anaerobiosis; Bacterial Typing Techniques; Base Composition; Body Fluids; Cytosol; Fatty Acids; Female; Firmicutes; Humans; Phylogeny; Sequence Homology, Nucleic Acid; Vaginosis, Bacterial
PubMed: 29931836
DOI: 10.1002/mbo3.661 -
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