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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 -
Cureus Feb 2024Introduction is an obligate anaerobic non-spore-forming Gram-negative bacilli. As a part of polymicrobial film, the activated virulence factor causes oral diseases like...
Introduction is an obligate anaerobic non-spore-forming Gram-negative bacilli. As a part of polymicrobial film, the activated virulence factor causes oral diseases like gingivitis and periodontitis. Decreased susceptibility of clinical strains of to different antibiotics including piperacillin and metronidazole raises concerns. There has been significant interest in the utility of plant phytocompounds as potent antibacterial agents. Aim The study aimed to look at the potential of two phytocompounds, eugenol and hydroxychavicol, for their ability to inhibit outer membrane protein (OmpH) of using computational tools. Results The study showed effective inhibition of the OmpH of by both eugenol and hydroxychavicol. The high probability to be active (Pa) value indicated the probability of true positive for the tested compounds for their predicted biological activity. There was strong reciprocity between the drug-likeliness and its binding affinity for the target protein, indicating an inhibitory nature. Conclusion The tested phytocompounds hydroxychavicol and eugenol showed potential inhibition of the OmpH protein of indicating its potential use as inhibitory compounds of the pathogen and future directions for the treatment of periodontitis and gingivitis.
PubMed: 38465032
DOI: 10.7759/cureus.53809 -
Alzheimer's Research & Therapy Feb 2024The relationship between periodontitis and Alzheimer's disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival...
BACKGROUND
The relationship between periodontitis and Alzheimer's disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival crevicular fluid (GCF) metabolic signatures in AD patients have rarely been characterized; thus, little evidence exists to support the oral-brain axis hypothesis. Therefore, our study aimed to characterize both the microbial community of subgingival plaque and the metabolomic profiles of GCF in patients with AD and amnestic mild cognitive impairment (aMCI) for the first time.
METHODS
This was a cross-sectional study. Clinical examinations were performed on all participants. The microbial community of subgingival plaque and the metabolomic profiles of GCF were characterized using the 16S ribosomal RNA (rRNA) gene high-throughput sequencing and liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) analysis, respectively.
RESULTS
Thirty-two patients with AD, 32 patients with aMCI, and 32 cognitively normal people were enrolled. The severity of periodontitis was significantly increased in AD patients compared with aMCI patients and cognitively normal people. The 16S rRNA gene sequencing results showed that the relative abundances of 16 species in subgingival plaque were significantly correlated with cognitive function, and LC-MS/MS analysis identified a total of 165 differentially abundant metabolites in GCF. Moreover, multiomics Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) analysis revealed that 19 differentially abundant metabolites were significantly correlated with Veillonella parvula, Dialister pneumosintes, Leptotrichia buccalis, Pseudoleptotrichia goodfellowii, and Actinomyces massiliensis, in which galactinol, sn-glycerol 3-phosphoethanolamine, D-mannitol, 1 h-indole-1-pentanoic acid, 3-(1-naphthalenylcarbonyl)- and L-iditol yielded satisfactory accuracy for the predictive diagnosis of AD progression.
CONCLUSIONS
This is the first combined subgingival microbiome and GCF metabolome study in patients with AD and aMCI, which revealed that periodontal microbial dysbiosis and metabolic disorders may be involved in the etiology and progression of AD, and the differential abundance of the microbiota and metabolites may be useful as potential markers for AD in the future.
Topics: Humans; Alzheimer Disease; Cross-Sectional Studies; RNA, Ribosomal, 16S; Chromatography, Liquid; Tandem Mass Spectrometry; Periodontitis; Microbiota; Cognitive Dysfunction
PubMed: 38373985
DOI: 10.1186/s13195-024-01402-1 -
BMC Infectious Diseases Sep 2023Dialister pneumosintes is an anaerobic, Gram negative bacillus, found in the human oral cavity and associated with periodontitis. It has also been isolated from gastric...
BACKGROUND
Dialister pneumosintes is an anaerobic, Gram negative bacillus, found in the human oral cavity and associated with periodontitis. It has also been isolated from gastric mucosa and stool samples. Recent case reports implicate D. pneumosintes in local infection such as dental root canals, sinusitis, Lemierres syndrome and brain abscesses, as well as distal infections of the liver and lung through haematogenous spread.
CASE PRESENTATION
We present a novel case of aortic graft infection and aortoenteric fistula (AEF) in a 75 year old Caucasian male, associated with D. pneumosintes bacteraemia. Microbiological evaluation of septic emboli in the lower limbs revealed other gastrointestinal flora. This suggests either AEF leading to graft infection and subsequent distal emboli and bacteraemia, or a dental origin of infection which seeded to the graft, resulting in AEF and systemic infection. To our knowledge this is the first report of D. pneumosintes associated aortic graft infection. The patient underwent surgical explantation, oversew of the aorta and placement of extra-anatomical bypass graft in conjunction with antimicrobial therapy, making a good recovery with discharge home after a 35-day hospital admission.
CONCLUSION
We report a case of Dialister pneumosintes bacteraemia associated with aortic graft infection. To our knowledge, vascular graft-associated infection with D. pneumosintes has not been reported before.
Topics: Male; Humans; Aged; Aorta; Veillonellaceae; Postoperative Complications; Sepsis; Bacteremia; Bacteroides
PubMed: 37726696
DOI: 10.1186/s12879-023-08584-3 -
International Journal of Molecular... May 2023According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant...
According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to characterize the cervicovaginal microbiota of women undergoing hysterectomy due to benign disease, atypical hyperplasia, and endometrial cancer; The study included 96 patients, who undergone surgical treatment due to benign uterine disease, precancerous endometrial lesion, and endometrial cancer. Quantitative and qualitative real-time PCR analysis of DNA isolated from vaginal fornix and endocervical canal samples was performed to detect the 19 most commonly identified microorganisms, including different spp., , , , and ; At least one of the tested microorganisms was identified in 88.5% of vaginal and 83.3% of cervical samples. was significantly more frequent in patients with benign condition, whereas and was more frequent in cancer patients; and which were identified as significantly more common in endometrial cancer vaginal samples, may be considered as potential endometrial cancer co-factors which promote/stimulate carcinogenesis. However, the exact mechanism of such activity remains unexplained and requires further investigations.
Topics: Humans; Female; Cervix Uteri; Vagina; Endometrial Neoplasms; Uterine Diseases; Microbiota; RNA, Ribosomal, 16S
PubMed: 37175971
DOI: 10.3390/ijms24098266 -
International Journal of Molecular... Feb 2023The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and...
The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty oral biopsies from HL ( = 9), PVL ( = 12), OSCC ( = 10), PVL-OSCC ( = 8), and healthy ( = 11) donors were obtained. The sequence of the V3-V4 region of the 16S rRNA gene was used to analyze the composition and diversity of bacterial populations. In the cancer patients, the number of observed amplicon sequence variants (ASVs) was lower and constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of and lower than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in , , , , , and ; PVL is enriched in , and ; OSCC is enriched in , and ; and PVL-OSCC is enriched in , and . There is differential dysbiosis in patients suffering from OPMDs and cancer. To the best of our knowledge, this is the first study comparing the oral microbiome alterations in these groups; thus, additional studies are needed.
Topics: Humans; Mouth Neoplasms; Carcinoma, Squamous Cell; Dysbiosis; RNA, Ribosomal, 16S; Leukoplakia, Oral; Microbiota
PubMed: 36834903
DOI: 10.3390/ijms24043466 -
Journal of Applied Oral Science :... 2023Based on a holistic concept of polymicrobial etiology, we have hypothesized that putative and candidate periodontal pathogens are more frequently detected in consortia...
BACKGROUND
Based on a holistic concept of polymicrobial etiology, we have hypothesized that putative and candidate periodontal pathogens are more frequently detected in consortia than alone in advanced forms of periodontal diseases (PD).
OBJECTIVE
To correlate specific consortia of periodontal pathogens with clinical periodontal status and severity of periodontitis.
METHODOLOGY
Subgingival biofilm was obtained from individuals with periodontal health (113, PH), gingivitis (91, G), and periodontitis (209, P). Genomic DNA was purified and the species Aggregatibacter actinomycetemcomitans (Aa), Aa JP2-like strain, Porphyromonas gingivalis (Pg), Dialister pneumosintes (Dp), and Filifactor alocis (Fa) were detected by PCR. Configural frequency and logistic regression analyses were performed to correlate microbial consortia and PD.
RESULTS
Aa + Pg in the presence of Dp (phi=0.240; χ2=11.9, p<0.01), as well as Aa JP2 + Dp + Fa (phi=0.186, χ2=4.6, p<0.05) were significantly more associated in advanced stages of P. The consortium Aa + Fa + Dp was strongly associated with deep pocketing and inflammation (p<0.001). The best predictors of disease severity (80% accuracy) included older age (OR 1.11 [95% CI 1.07 - 1.15], p<0.001), Black/African-American ancestry (OR 1.89 [95% CI 1.19 - 2.99], p=0.007), and high frequency of Aa + Pg + Dp (OR 3.04 [95% CI 1.49 - 6.22], p=0.002).
CONCLUSION
Specific microbial consortia of putative and novel periodontal pathogens, associated with demographic parameters, correlate with severe periodontitis, supporting the multifactorial nature of PD.
Topics: Humans; Periodontal Diseases; Periodontitis; Porphyromonas gingivalis; Bacteroides; Aggregatibacter actinomycetemcomitans; Patient Acuity
PubMed: 36629716
DOI: 10.1590/1678-7757-2022-0359 -
Frontiers in Cellular and Infection... 2022Coronavirus disease 2019 (COVID-19) is currently a severe threat to global public health, and the immune response to COVID-19 infection has been widely investigated....
Coronavirus disease 2019 (COVID-19) is currently a severe threat to global public health, and the immune response to COVID-19 infection has been widely investigated. However, the immune status and microecological changes in the respiratory systems of patients with COVID-19 after recovery have rarely been considered. We selected 72 patients with severe COVID-19 infection, 57 recovered from COVID-19 infection, and 65 with non-COVID-19 pneumonia, for metatranscriptomic sequencing and bioinformatics analysis. Accordingly, the differentially expressed genes between the infected and other groups were enriched in the chemokine signaling pathway, NOD-like receptor signaling pathway, phagosome, TNF signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, and C-type lectin receptor signaling pathway. We speculate that , CD74, and TNFSF15 may serve as disease biomarkers in COVID-19. Additionally, principal coordinate analysis revealed significant differences between groups. In particular, frequent co-infections with the genera , , , and , among others, were found in COVID-19 patients. Moreover, the random forest prediction model with differential genes showed a mean area under the curve (AUC) of 0.77, and , , , , , , , , , and were identified as the most important genes distinguishing the infected group from the recovered group. sp. FJAT.14266, , and were selected as candidate microbial markers for monitoring the recovery of COVID patients. These results will facilitate the diagnosis, treatment, and prognosis of COVID patients recovering from severe illness.
Topics: Humans; COVID-19; Tumor Necrosis Factor Ligand Superfamily Member 15
PubMed: 36483456
DOI: 10.3389/fcimb.2022.1011672 -
IMeta Dec 2022The dysbiosis of the gut microbiome is one of the pathogenic factors of nonalcoholic fatty liver disease (NAFLD) and also affects the treatment and intervention of...
The dysbiosis of the gut microbiome is one of the pathogenic factors of nonalcoholic fatty liver disease (NAFLD) and also affects the treatment and intervention of NAFLD. Among gut microbiomes, keystone species that regulate the integrity and stability of an ecological community have become the potential intervention targets for NAFLD. Here, we collected stool samples from 22 patients with nonalcoholic steatohepatitis (NASH), 25 obese patients, and 16 healthy individuals from New York for 16S rRNA gene sequencing. An algorithm was implemented to identify keystone species based on causal inference theories and dynamic intervention simulation. External validation was performed in an independent cohort from California. Eight keystone species in the gut of NAFLD, represented by , and , were identified, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome with 92.3% recovery. These keystone species regulate intestinal amino acid metabolism and acid-base environment to promote the growth of the butyrate-producing Lachnospiraceae and Ruminococcaceae species that are significantly reduced in NAFLD patients. Our findings demonstrate the importance of keystone species in restoring the microbial composition toward a normal gut microbiome, suggesting a novel potential microbial treatment for NAFLD.
PubMed: 38867895
DOI: 10.1002/imt2.61 -
Infection and Drug Resistance 2022Although is a commensal microorganism of the oral cavity, it may sometimes cause severe systemic infections. We report a case of Lemierre syndrome (LS), which developed...
Although is a commensal microorganism of the oral cavity, it may sometimes cause severe systemic infections. We report a case of Lemierre syndrome (LS), which developed after infection, in a 73-year-old Japanese woman who was admitted to the hospital for throat pain, neck swelling, and fever for 3 days. She had a 3-month history of neglected dental caries, gingivitis, and periodontitis. Physical examination revealed right tonsillar erythema and swelling, and computed tomography (CT) showed peritonsillar and retropharyngeal abscesses. Ampicillin/sulbactam was promptly administered after collecting two sets of blood cultures. Surgical drainage for peritonsillar and retropharyngeal abscesses was also conducted on the second hospital day. Although only commensal oral microflora grew in the culture from the drained pus, Gram-negative bacilli were confirmed in the anaerobic blood cultures. Metronidazole was administered intravenously; however, the fever and neck swelling persisted. Repeat CT performed on the fifth hospital day revealed right internal jugular vein thrombosis, a known complication of tonsillitis and pharyngitis once the infection extends beyond the oropharynx. We diagnosed she had coexisting LS, and anticoagulant therapy was added to her treatment regimen. Her condition improved, and she was discharged after completing 3 weeks of antibiotics. Conventional methods failed to identify the isolated bacterium, and 16S rRNA sequencing ultimately identified it as . In a literature review of bacteremia due to , poor oral hygiene was considered a probable risk factor for invasive infection. We consider this to be the case in our patient who presented with dental caries, gingivitis, and periodontitis. In addition, all cases revealed that the 16S rRNA gene sequencing is useful for identifying this species. Although the diagnosis of LS by physical examination is difficult, physicians should always consider it as a potential complication of infections in the pharyngeal area.
PubMed: 35668853
DOI: 10.2147/IDR.S359074