-
World Journal of Gastroenterology Nov 2021Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients. Little is known about the intestinal nonpathogenic bacterial composition of...
BACKGROUND
Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients. Little is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma (HCC) patients treated by immunotherapy.
AIM
To determine whether there is a correlation between gut bacterial composition and prognosis in HCC patients.
METHODS
From September 2019 to March 2020, we prospectively collected fecal samples and examined the gut microbiome of 8 advanced HCC patients treated with nivolumab as a second- or third-line systemic treatment. Fecal samples were collected before the start of immunotherapy. Fecal samples of patients with progression during treatment were collected at the time of progression, and fecal samples of patients who showed good response to nivolumab were collected after 5-7 mo as follow-up. Metagenomic data from 16S ribosomal RNA sequencing were analyzed using CLC Genomics Workbench. Microbiome data were analyzed according to therapeutic response.
RESULTS
All 8 patients were male, of which 6 had underlying chronic hepatitis B. A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy ( = 0.036). The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic response. There was no significant difference in the diversity or composition of the patient gut microbiome according to the immunotherapy used. Several taxa specific to therapeutic response were designated as follows: sp., and for the non-responders; sp. and for the responders. Of note, a skewed ratio and a low ratio can serve as predictive markers of non-response, whereas the presence of species predicts a good response.
CONCLUSION
The current presumptive study suggests a potential role for the gut microbiome as a prognostic marker for the response to nivolumab in treatment of HCC patients.
Topics: Carcinoma, Hepatocellular; Feces; Gastrointestinal Microbiome; Humans; Liver Neoplasms; Male; Nivolumab; Phylogeny; RNA, Ribosomal, 16S
PubMed: 34876793
DOI: 10.3748/wjg.v27.i42.7340 -
Clinical Oral Investigations May 2018This short-term randomized controlled trial evaluated the effectiveness of photodynamic therapy (PDT) on clinical success (periapical healing) and on the microbiota of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
This short-term randomized controlled trial evaluated the effectiveness of photodynamic therapy (PDT) on clinical success (periapical healing) and on the microbiota of primary endodontic infections.
METHODS
Thirty-two patients presenting mandibular molars with apical periodontitis (one tooth/patient) were selected and randomly allocated into two therapeutic groups: control (chemo-mechanical debridement [CMD]; n = 16) and PDT (CMD + PDT; n = 16). All teeth in both groups had intracanal medication with calcium hydroxide for 7 days before final obturation. Follow-up radiographs were made at 3 and 6 months. Periapical healing was evaluated by the periapical index (PAI). Samples were obtained at baseline, after CMD with or without PDT, and just before root filling to determine the frequency and levels of 37 taxa by checkerboard.
RESULTS
Significant decreases in PAI scores were observed in both groups over time, although at 6 months, the PDT group presented a significantly better healing score than the control (p < 0.05). At baseline, the most prevalent species in all samples were Candida albicans (46.9%), Dialister pneumosintes (31.2%), Prevotella nigrescens (28.2%), Prevotella tannerae (28.1%), and Peptostreptococcus anaerobius (25%). Most species reduced over time in both groups, and no significant differences in frequency and levels of the tested species were observed between groups in any time point evaluated. C. albicans and D. pneumosintes were still detected in high frequency in both groups at 3 months post-therapy.
CONCLUSIONS
Conventional endodontic therapy with or without PDT is effective in reducing microbial load, resulting in periapical healing. Nevertheless, adjunctive PDT provides better periapical healing at 6-month follow-up.
CLINICAL RELEVANCE
Teeth with apical periodontitis treated with PDT adjunct to conventional treatment would demonstrate superior healing and reduction of microorganisms.
Topics: Adult; DNA Probes; Female; Humans; Male; Microbiota; Pain Measurement; Periapical Periodontitis; Photochemotherapy; Root Canal Filling Materials; Root Canal Therapy; Treatment Outcome
PubMed: 29116494
DOI: 10.1007/s00784-017-2270-4 -
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 -
NPJ Biofilms and Microbiomes 2017We have previously reported that oral biofilms in clinically healthy smokers are pathogen-rich, and that this enrichment occurs within 24 h of biofilm formation. The...
We have previously reported that oral biofilms in clinically healthy smokers are pathogen-rich, and that this enrichment occurs within 24 h of biofilm formation. The present investigation aimed to identify a mechanism by which smoking creates this altered community structure. By combining in vitro microbial-mucosal interface models of commensal (consisting of and and pathogen-rich (comprising and , and communities with metatranscriptomics, targeted proteomics and fluorescent microscopy, we demonstrate that smoke exposure significantly downregulates essential metabolic functions within commensal biofilms, while significantly increasing expression of virulence genes, notably lipopolysaccharide (LPS), flagella and capsule synthesis. By contrast, in pathogen-rich biofilms several metabolic pathways were over-expressed in response to smoke exposure. Under smoke-rich conditions, epithelial cells mounted an early and amplified pro-inflammatory and oxidative stress response to these virulence-enhanced commensal biofilms, and a muted early response to pathogen-rich biofilms. Commensal biofilms also demonstrated early and widespread cell death. Similar results were observed when smoke-free epithelial cells were challenged with smoke-conditioned biofilms, but not vice versa. In conclusion, our data suggest that smoke-induced transcriptional shifts in commensal biofilms triggers a florid pro-inflammatory response, leading to early commensal death, which may preclude niche saturation by these beneficial organisms. The cytokine-rich, pro-oxidant, anaerobic environment sustains inflammophilic bacteria, and, in the absence of commensal antagonism, may promote the creation of pathogen-rich biofilms in smokers.
PubMed: 29081982
DOI: 10.1038/s41522-017-0033-2 -
BMJ Case Reports Mar 2022A man in his twenties with a history of recurrent sinusitis was urgently referred to the emergency department (ED) by an out-of-hours general practitioner following a...
A man in his twenties with a history of recurrent sinusitis was urgently referred to the emergency department (ED) by an out-of-hours general practitioner following a 2-day history of increasing right eye pain, redness and swelling after a week of coryzal symptoms. He denied visual impairment and any history of recent dental pain or procedures. Initial assessment in ED noted fever, tachycardia and hypotension. Video consultation with ophthalmologist in the ED identified proptosis, periorbital erythema and chemosis with full eye movement solely affecting the right eye. Visual acuity of 6/6 was confirmed in both eyes. After review by the ear, nose and throat (ENT) team, a diagnosis of sinogenic right orbital cellulitis was made, empirical antibiotics started and care transferred to the ENT team for immediate surgical intervention. 48 hours postoperatively, the patient acutely deteriorated, developing ophthalmoplegia and visual acuity of 6/95 in the right eye. Repeat imaging demonstrated a deteriorating picture and urgent surgery was organised at a neighbouring hospital's specialist ENT unit combined with a change to his antibiotics. On day 4, 1 day following transfer, an anaerobic bacterium, was isolated from blood cultures collected on admission. The patient improved clinically following the second surgery and targeted antimicrobial therapy, eventually being discharged 10 days after initial presentation. In addition to , the Anaerobic Reference Unit (Cardiff) identified two further anaerobic bacteria, and This paper presents the first documented case of polymicrobial anaerobic orbital cellulitis secondary to acute bacterial sinusitis. Moreover, this case underpins the importance of broad empirical antibiotics coupled with surgical source control to effectively manage a rare but sight-threatening and life-threatening disease.
Topics: Anaerobiosis; Anti-Bacterial Agents; Base Composition; Humans; Male; Orbital Cellulitis; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Tomography, X-Ray Computed
PubMed: 35351758
DOI: 10.1136/bcr-2021-248473 -
Journal of Endodontics Aug 2016The purpose of this study was to combine multiple displacement amplification and checkerboard DNA-DNA hybridization to qualitatively and quantitatively evaluate the...
INTRODUCTION
The purpose of this study was to combine multiple displacement amplification and checkerboard DNA-DNA hybridization to qualitatively and quantitatively evaluate the microbiota present in infections refractory to endodontic treatment.
METHODS
The subjects of this study were 40 patients presenting with periapical lesions refractory to endodontic treatment. Samples were taken by scraping or filing root canal walls with a #10 K-type hand file. Sample DNA was amplified by multiple displacement amplification, and the levels of 107 bacterial taxa were analyzed by checkerboard DNA-DNA hybridization. The taxa were divided into 3 distinct microbial populations depending on their mean proportion in samples (% DNA probe counts ± standard error of the mean) as follows: dominant (≥3.0%), subdominant (>1.6%-3.0%), and residual (≤1.6%) populations. The significance of differences was determined using the Mann-Whitney test.
RESULTS
The taxa present with the highest mean proportions (constituting the dominant population) were Corynebacterium diphtheriae (8.03 ± 0.98), Porphyromonas gingivalis (5.42 ± 2.09), Streptococcus sobrinus (5.33 ± 0.69), and Stenotrophomonas maltophilia (4.72 ± 1.73). Among the subdominant population were Eubacterium saphenum (3.85 ± 1.06), Helicobacter pylori (3.16 ± 0.62), Dialister pneumosintes (3.12 ± 1.1), Clostridium difficile (2.74 ± 0.41), Enterobacter agglomerans (2.64 ± 0.54), Salmonella enterica (2.51 ± 0.52), Mobiluncus mulieris (2.44 ± 0.6), and Klebsiella oxytoca (2.32 ± 0.66). In the population of bacteria present at the lowest mean proportions (the residual population), Bacteroides ureolyticus (0.04 ± 0.01), Haemophilus influenzae (0.04 ± 0.02), and Prevotella oris (0.01 ± 0.01) were found at the lowest mean proportions. Enterococcus faecalis was detected in the residual population (0.52 ± 0.26).
CONCLUSIONS
The microbial climax community in teeth refractory to endodontic treatment not only harbors medically important species but also contains distinct microbial consortia present with different population levels.
Topics: Bacteria; DNA Probes; DNA, Bacterial; Dental Pulp Cavity; Dental Pulp Necrosis; Humans; Microbiota; Nucleic Acid Hybridization; Periapical Diseases; Root Canal Therapy
PubMed: 27377440
DOI: 10.1016/j.joen.2016.05.014 -
Frontiers in Cellular and Infection... 2015Patients with acquired immunodeficiency syndrome (AIDS) are at high risk of opportunistic infections. Oral manifestations have been associated with the level of...
Patients with acquired immunodeficiency syndrome (AIDS) are at high risk of opportunistic infections. Oral manifestations have been associated with the level of immunosuppression, these include periodontal diseases, and understanding the microbial populations in the oral cavity is crucial for clinical management. The aim of this study was to examine the salivary bacterial diversity in patients newly admitted to the AIDS ward of the Public Health Clinical Center (China). Saliva samples were collected from 15 patients with AIDS who were randomly recruited between December 2013 and March 2014. Extracted DNA was used as template to amplify bacterial 16S rRNA. Sequencing of the amplicon library was performed using a 454 GS-FLX Titanium sequencing platform. Reads were optimized and clustered into operational taxonomic units for further analysis. A total of 10 bacterial phyla (106 genera) were detected. Firmicutes, Bacteroidetes, and Proteobacteria were preponderant in the salivary microbiota in AIDS patients. The pathogen, Capnocytophaga sp., and others not considered pathogenic such as Neisseria elongata, Streptococcus mitis, and Mycoplasma salivarium but which may be opportunistic infective agents were detected. Dialister pneumosintes, Eubacterium infirmum, Rothia mucilaginosa, and Treponema parvum were preponderant in AIDS patients with periodontitis. Patients with necrotic periodontitis had a distinct salivary bacterial profile from those with chronic periodontitis. This is the first study using advanced sequencing techniques focused on hospitalized AIDS patients showing the diversity of their salivary microbiota.
Topics: Acquired Immunodeficiency Syndrome; Adult; Bacteria; Biota; China; Cluster Analysis; DNA, Bacterial; DNA, Ribosomal; Female; Gingivitis; Humans; Male; Middle Aged; Periodontal Diseases; Phylogeny; RNA, Ribosomal, 16S; Saliva; Sequence Analysis, DNA
PubMed: 26191508
DOI: 10.3389/fcimb.2015.00055 -
Journal of Endodontics Nov 2014This clinical study has investigated the antigenic activity of bacterial contents from exudates of acute apical abscesses (AAAs) and their paired root canal contents... (Comparative Study)
Comparative Study
INTRODUCTION
This clinical study has investigated the antigenic activity of bacterial contents from exudates of acute apical abscesses (AAAs) and their paired root canal contents regarding the stimulation capacity by levels of interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF-α) throughout the root canal treatment against macrophage cells.
METHODS
Paired samples of infected root canals and exudates of AAAs were collected from 10 subjects. Endodontic contents were sampled before (root canal sample [RCS] 1) and after chemomechanical preparation (RCS2) and after 30 days of intracanal medication with calcium hydroxide + chlorhexidine gel (Ca[OH]2 + CHX gel) (RCS3). Polymerase chain reaction (16S rDNA) was used for detection of the target bacteria, whereas limulus amebocyte lysate was used to measure endotoxin levels. Raw 264.7 macrophages were stimulated with AAA exudates from endodontic contents sampled in different moments of root canal treatment. Enzyme-linked immunosorbent assays were used to measure the levels of TNF-α and IL-1 beta.
RESULTS
Parvimonas micra, Porphyromonas endodontalis, Dialister pneumosintes, and Prevotella nigrescens were the most frequently detected species. Higher levels of endotoxins were found in samples from periapical exudates at RCS1 (P < .005). In fact, samples collected from periapical exudates showed a higher stimulation capacity at RCS1 (P < .05). A positive correlation was found between endotoxins from exudates with IL-1 beta (r = 0.97) and TNF-α (r = 0.88) production (P < .01). The significant reduction of endotoxins and bacterial species achieved by chemomechanical procedures (RCS2) resulted in a lower capacity of root canal contents to stimulate the cells compared with that at RCS1 (P < .05). The use of Ca(OH)2 + CHX gel as an intracanal medication (RCS3) improved the removal of endotoxins and bacteria from infected root canals (P < .05) whose contents induced a lower stimulation capacity against macrophages cells at RCS1, RCS2, and RCS3 (P < .05).
CONCLUSIONS
AAA exudates showed higher levels of endotoxins and showed a greater capacity of macrophage stimulation than the paired root canal samples. Moreover, the use of intracanal medication improved the removal of bacteria and endotoxins from infected root canals, which may have resulted in the reduction of the inflammatory potential of the root canal content.
Topics: Anti-Infective Agents, Local; Antigens, Bacterial; Calcium Hydroxide; Cell Line; Chlorhexidine; Dental Pulp Cavity; Endotoxins; Gram-Negative Anaerobic Straight, Curved, and Helical Rods; Humans; Interleukin-1beta; Macrophage Activation; Peptostreptococcus; Periapical Abscess; Porphyromonas endodontalis; Prevotella nigrescens; Root Canal Irrigants; Root Canal Preparation; Tumor Necrosis Factor-alpha
PubMed: 25205261
DOI: 10.1016/j.joen.2014.06.019