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Objectives Helicobacter pylori infection causes atrophic gastritis, which affects the gut microbiome; the gastric acid concentration depends on the degree of atrophic gastritis. Helicobacter pylori eradication also affects gastric acidity. Here, we determined the differences in the post-eradication changes in the gut microbiome in relation to the progression of gastric atrophy. Materials and methods Ten patients were included in the closed group and five in the open group, consisting of patients with non-progressive and progressive atrophy, respectively, diagnosed by endoscopy. The faecal microbiome was analysed and compared among three time-points: before eradication, 8 weeks after eradication, and 6 months after eradication. The microbiome was analysed by targeting 16S rRNA using Illumina Miseq. Results The relative abundance of 14 genera significantly differed between the closed and open groups before eradication, but only 12 and 6 genera presented a significant difference in the relative abundance at 8 weeks and 6 months after eradication, respectively. Of the 12 genera that differed between the closed and open groups before eradication, 8 genera, namely, Actinomyces, Aggregatibacter, Campylobacter, Granulicatella, Pyramidobacter, Streptococcus, Cardiobacterium, and Haemophilus, were oral-origin bacteria. Longitudinal changes showed that Haemophilus and Catenibacterium were consistently significantly more abundant in the open group than in the closed group during the follow-up period. Conclusion The gut microbiome substantially differed depending on the progression of gastric atrophy, but this difference was decreased by eradication, especially the differences in the number of oral bacteria in the gut. Eradication therapy may improve dysbiosis that result from gastric atrophy.

Obstructive sleep apnea–hypopnea syndrome (OSAHS) is an independent risk factor for cardiovascular diseases, including hypertension. In our previous study, it was demonstrated that oral microbiota alteration in patients with OSAHS, particularly in the genera Aggregatibacter and Porphyromonas, may influence the development of hypertension. Continuous positive airway pressure (CPAP) is the main therapy for OSAHS and OSAHS-associated hypertension. However, the role of oral microbiota post CPAP treatment remains unknown. We conducted 16S rDNA pyrosequencing and bioinformatic analyses to compare the bacterial composition of oral specimens from patients with OSAHS before and after overnight CPAP treatment. This approach enabled a relatively comprehensive description of oral microbiota, with decreases in Gemella and increases in Staphylococcus, f_Lachnospiraceae, Parabacteroides, and f_Ruminococcaceae after CPAP treatment. Alteration of oral microbiota may shed new insight on the underlying pathogenesis of OSAHS-associated hypertension.

Aggregatibacter actinomycetemcomitans, an etiological agent associated with periodontitis, endocarditis, and other infections, has rarely been implicated in spondylitis. A 70-year-old man with aortic valve replacement presented with a 4-month history of lower back pain and was diagnosed with spondylitis. Prolonged incubation of blood cultures and a biopsy yielded A. actinomycetemcomitans. Concurrent infective endocarditis (IE) was probable considering the infectious organism and the patients' prosthetic valve. The patient was treated with ceftriaxone and recovered well. Pyogenic spondylitis with possible concurrent IE may be caused by A. actinomycetemcomitans. Extended incubation and repeated cultures should be considered if Haemophilus spp., Aggregatibacter spp, Cardiobacterium spp, Eikenella spp, and Kingella spp. (HACEK) infection is suspected.

Periodontal disease is an inflammatory condition around the teeth which affects 20-50% of the worldwide population. In periodontal disease, the bacterial plaque destroys the epithelium of the periodontal pocket and breaks the barrier that separates the tissue and the circulation, allowing oral bacteria and their endotoxins and exotoxins to enter the bloodstream. This can cause health problems, such as atherosclerosis. Aggregatibacter actinomycetemcomitans (Aa) is commonly found in patients with periodontitis and the number of Aa is associated with atherosclerotic lesion size in humans. This review focuses on Aa and atherosclerosis with an emphasis on the interaction of Aa with cell types involved in atherosclerosis formation.

There has been an indiscriminate use of commercial antimicrobials in the previous decades, leading to emergence of multidrug resistant bacteria. This has become a frequent occurrence, so natural antimicrobial agents have grabbed attention of researchers as potential alternatives. Of particular interest is cow dung which has been shown to have antibacterial and antiseptic properties. It is known to be used predominantly in rural areas. This paper aims to evaluate the antibacterial activity of Goshala Activated Carbon toothpowder against three strains of periodontopathogennic and cariogenic bacteria. Standardized strains of Streptococcus mutans, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were cultured in BHI (Brain Heart Infusion Broth) media and Minimum Inhibitory Concentration (MIC) of Activated Carbon tooth powder was assessed by serial dilution method. Likewise, Amoxicillin, Metronidazole and Chlorhexidine were tested against the same pathogens. Porphyromonas gingivalis, Streptococcus mutans and Aggregatibacter actinomycetemcomitans were shown to be sensitive at an MIC of 50mg/ml, 25mg/ml and 0.8mg/ml for activated carbon toothpowder respectively. Given some limitations of this study, we can conclude that activated carbon powder presents a ray of hope in developing a targeted agent for aggressive periodontitis patients.

Hypericum perforatum is a useful plant because of its biological features, such as bactericidal, virucidal, and fungicidal effects. Elimination of periodontal pathogens, including Aggregatibacter a...

The Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella (HACEK) group genus Eikenella contained a single species, Eikenella corrodens, for many years. In November 2019, Eikenella exigua was described after recovery from a brain abscess and blood culture in Norway. Coincidentally, characterization of 22 Gram-negative bacteria resembling Eikenella from 17 Canadian patients had been underway. Seven isolates from five patients were conclusively identifiable as E. corrodens . One (NML 120819) was deemed to represent a species of the genus Eikenella most closely related to E. corrodens . Fourteen isolates had 97.6 to 98.8% similarities to E. corrodens by 16S rRNA gene sequencing, forming three distinct groups by genome analyses. The largest contained ten anaerobic isolates from eight patients recovered from blood, brain, bone and other abscesses; upon re-evaluation, this group was found to be most consistent with E. exigua . A second facultatively anaerobic clade consisted of two ocular isolates from one patient and a sinus isolate from a second patient. The third taxon consisted of a single strictly anaerobic blood culture isolate. The novel taxa, like E. corrodens , were poorly reactive biochemically and difficult to discern from each other phenotypically and chemotaxonomically, including by cellular fatty acids. MALDI-TOF (Bruker) and whole-genome sequencing were used to further characterize isolates. Draft genomes for the strains had similar DNA G+C contents (55.38–58.53 mol%) while sizes varied from 1.82 Mb to 2.54 Mb. We propose here emendations of the genus Eikenella and the species Eikenella exigua , as well as describing Eikenella halliae sp. nov. NML 130454T (=LMG 30894T=NCTC 14180T) and Eikenella longinqua sp. nov. NML 02-A-017T (=LMG 30896T=NCTC 14179T), on the basis of these findings.

Aims: To explore the tongue coating microbiota composition in patients with atrophic gastritis by using the 16S rRNA gene sequencing technology. Methods: The study included 29 atrophic gastritis patients and 29 age and gender-matched non-atrophic gastritis controls. By sequencing the V3-V4 region of the 16S rRNA, we investigated the microbial community structure and diversity on the tongue coating. Results: There was no significant difference in the microbial diversity on the tongue coating between the two groups. However, compared with the control, the atrophic gastritis group had a smaller number of operational taxonomic units (OTUs). At the class level, patients with atrophic gastritis had lower relative abundances of Betaproteobacteria and Spirochaetia than the control group. At the gene level, the abundance of Neisseria and Aggregatibacter in atrophic gastritis group had significantly decreased compared with control ones. Furthermore, functional prediction revealed that 24 metabolic pathways significantly differed between the two groups. Conclusions: Our findings provide novel evidence that tongue coating microbiota may be a biomarker for characterizing patient with atrophic gastritis, but its mechanism needs to be further elaborated.

Purpose of review Gram-negative bacilli (GNB) cause between 1% and 10% of infective endocarditis (IE). Most episodes are caused by microorganisms of the Haemophilus spp., Aggregatibacter spp. Cardiobacterium spp., Eikenella spp., and Kingella spp (HACEK) group. The frequency of IE caused by non-HACEK (GNB-IE) has increased in recent years. Uncertainties persist regarding its best medical treatment and the appropriateness and timing of surgical treatment. In addition, there are new drugs with activity against multiresistant microorganisms, of which there is little experience in this disease. We review this topic by answering the most frequently asked questions that arise among our colleagues. Recent findings HACEK microorganisms cause 1.5-2% of IE with only a 2% mortality. In contrast, non-HACEK GNB-IE accounts for 2.5-3% of all IE cases and is associated with nosocomial acquisition, advanced age, solid organ transplantation and 20-30% mortality. Drug addiction is important in areas with epidemic opioid abuse. Summary The frequency of IE caused by GNB has been modified in recent years. HACEK episodes are no longer treated with ampicillin and aminoglycosides. In non-HACEK GNB-IE, combination therapy with a beta-lactam and a quinolone or aminoglycoside is recommended. The surgical indication and its value are evident in many patients. Management should rely on a collaborative group with experience in this disease.

Made available in DSpace on 2022-04-29T08:34:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Background and objective: Previous studies have demonstrated an association between the IL10 promoter rs6667202 (C > A) single-nucleotide polymorphism (SNP) and grade C, stage 3 or 4 periodontitis (Perio4C) in the Brazilian population, where the altered A allele was detected more frequently in these patients. However, no functional analysis of this variation has yet been performed. Thus, the objective of this preliminary study was to evaluate the functionality of rs6667202 in gingival fibroblasts (GFs) of individuals with Perio4C and with periodontal health (PH) stimulated with Aggregatibacter actinomycetencomitans protein extract (AaPE). Methods: Patients with PH and Perio4C were segregated according to their genotype (AA, AC, or CC), and a biopsy was performed to establish the culture of the GFs. After GFs exposure to AaPE at 5 µg/ml for 1.5 h, RNA was extracted to analyze IL10 expression by qPCR. Aliquots of the cell's supernatant were subjected to immunoenzymatic analysis (MAGpix) to detect interleukin-10 (IL-10). Results: In PH, the genotypes AA and AC are related to less expression of IL10 (p = 0.027 and p 0.05), although a lower IL-10 expression and release compared with PH CC was seen (p = 0.033 and p

Diabetes is closely associated with periodontitis, however, the effects of type 2 diabetes and metformin treatment on the salivary microbiota in chronic periodontitis patients are still insufficiently studied. Saliva was collected from ten patients with moderate to severe chronic periodontitis (CP group) and 20 patients with type 2 diabetes mellitus (T2DM) and moderate to severe chronic periodontitis (ten patients were newly diagnosed with diabetes without drug treatment (DM group), and ten patients were treated with metformin (CP-DM-MET group)). Total DNA was extracted. DNA amplicons of the V3-V4 hypervariable regions of the 16S rRNA gene were generated and subjected to high-throughput sequencing. There was no significant difference in the alpha diversity of the salivary microbiota (Observed_Species, Shannon, Simpson, ACE, Chao1 index) among the three groups. The dominant phyla with relative abundances greater than 1% were Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, Fusobacteriota, and Spirochaetota, and no significant difference was found among the three groups. Compared with the CP group, the relative abundance of twelve genera was found changed in CP-DM group, for example, Aggregatibacter, Unclassified_f_Neisseriaceae, Parvimonas, Erysipelotrichace_UCG-006, Atopobium, and Endomicrobium et al. Metformin treatment could partly restore the abundance of several genera in CP-DM, such as Acholeplasma and Comamonas. Compared with the CP group, genus Lactobacillus, Parvimonas, Norank_f_norank_o_Absconditabacteriales_SR1, and Acholeplasma changed significantly in CP-DM-MET group. Plaque index (PLI) was positively correlated with Prevotella and Lactobacillus but negatively correlated with Haemophilus, Lautropia, Unclassified_f_Pasteurellaceae, and TM7x. In conclusion, there was a significant difference in the salivary microbiota of patients with chronic periodontitis complicated by T2DM. Treatment with metformin partially alleviated the alteration in salivary microbiota caused by T2DM.

ObjectiveMicroorganisms play a key role in the initiation and progression of periodontal disease. Research studies have focused on seeking specific microorganisms for diagnosing and monitoring the outcome of periodontitis treatment. Large samples may help to discover novel potential biomarkers and capture the common characteristics among different periodontitis patients. This study examines how to screen and merge high-quality periodontitis-related sequence datasets from several similar projects to analyze and mine the potential information comprehensively.MethodsIn all, 943 subgingival samples from nine publications were included based on predetermined screening criteria. A uniform pipeline (QIIME2) was applied to clean the raw sequence datasets and merge them together. Microbial structure, biomarkers, and correlation network were explored between periodontitis and healthy individuals. The microbiota patterns at different periodontal pocket depths were described. Additionally, potential microbial functions and metabolic pathways were predicted using PICRUSt to assess the differences between health and periodontitis.ResultsThe subgingival microbial communities and functions in subjects with periodontitis were significantly different from those in healthy subjects. Treponema, TG5, Desulfobulbus, Catonella, Bacteroides, Aggregatibacter, Peptostreptococcus, and Eikenella were periodontitis biomarkers, while Veillonella, Corynebacterium, Neisseria, Rothia, Paludibacter, Capnocytophaga, and Kingella were signature of healthy periodontium. With the variation of pocket depth from shallow to deep pocket, the proportion of Spirochaetes, Bacteroidetes, TM7, and Fusobacteria increased, whereas that of Proteobacteria and Actinobacteria decreased. Synergistic relationships were observed among different pathobionts and negative relationships were noted between periodontal pathobionts and healthy microbiota.ConclusionThis study shows significant differences in the oral microbial community and potential metabolic pathways between the periodontitis and healthy groups. Our integrated analysis provides potential biomarkers and directions for in-depth research. Moreover, a new method for integrating similar sequence data is shown here that can be applied to other microbial-related areas.

Significance Studies of the microbial communities living in association with animals, with plants, and in the environment have revolutionized our understanding of microbial diversity, but the interactions between these microbes remain largely elusive. Here, we characterize pairwise interactions during infection between a human pathogen and 25 diverse microbes from both sympatric (same) and allopatric (different) environments. We demonstrate that allopatric microbes increase survival of the pathogen. Furthermore, we identify the large set of genes (33% of the genome) that are essential for pathogen survival during coinfection, including a core set that are also required in monoinfection and diverse accessory essential genes. This work advances our understanding of how coinfecting microbes modulate the genes required for survival in vivo., Recent evidence suggests that the genes an organism needs to survive in an environment drastically differ when alone or in a community. However, it is not known if there are universal functions that enable microbes to persist in a community and if there are functions specific to interactions between microbes native to the same (sympatric) or different (allopatric) environments. Here, we ask how the essential functions of the oral pathogen Aggregatibacter actinomycetemcomitans change during pairwise coinfection in a murine abscess with each of 15 microbes commonly found in the oral cavity and 10 microbes that are not. A. actinomycetemcomitans was more abundant when coinfected with allopatric than with sympatric microbes, and this increased fitness correlated with expanded metabolic capacity of the coinfecting microbes. Using transposon sequencing, we discovered that 33% of the A. actinomycetemcomitans genome is required for coinfection fitness. Fifty-nine “core” genes were required across all coinfections and included genes necessary for aerobic respiration. The core genes were also all required in monoinfection, indicating the essentiality of these genes cannot be alleviated by a coinfecting microbe. Furthermore, coinfection with some microbes, predominately sympatric species, induced the requirement for over 100 new community-dependent essential genes. In contrast, in other coinfections, predominately with nonoral species, A. actinomycetemcomitans required 50 fewer genes than in monoinfection, demonstrating that some allopatric microbes can drastically alleviate gene essentialities. These results expand our understanding of how diverse microbes alter growth and gene essentiality within polymicrobial infections.

Aggregatibacter and Haemophilus species are relevant human commensals and opportunistic pathogens. Consequently, their bacteriophages may have significant impact on human microbial ecology and pathologies. Our aim was to reveal the prevalence and diversity of bacteriophages infecting Aggregatibacter and Haemophilus species that colonize the human body. Genome mining with comparative genomics, screening of clinical isolates, and profiling of metagenomes allowed characterization of 346 phages grouped in 52 clusters and 18 superclusters. Less than 10% of the identified phage clusters were represented by previously characterized phages. Prophage diversity patterns varied significantly for different phage types, host clades, and environmental niches. A more diverse phage community lysogenizes Haemophilus influenzae and Haemophilus parainfluenzae strains than Aggregatibacter actinomycetemcomitans and “Haemophilus ducreyi”. Co-infections occurred more often in “H. ducreyi”. Phages from Aggregatibacter actinomycetemcomitans preferably lysogenized strains of specific serotype. Prophage patterns shared by subspecies clades of different bacterial species suggest similar ecoevolutionary drivers. Changes in frequencies of DNA uptake signal sequences and guanine–cytosine content reflect phage-host long-term coevolution. Aggregatibacter and Haemophilus phages were prevalent at multiple oral sites. Together, these findings should help exploring the ecoevolutionary forces shaping virus-host interactions in the human microbiome. Putative lytic phages, especially phiKZ-like, may provide new therapeutic options.

HACEK organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella species) are rare causes of endocarditis. HACEK organisms are fastidious and may escape detection by culture techniques, but the use of molecular studies may aid diagnosis. A 10-year review of pediatric HACEK endocarditis cases at Texas Children's Hospital identified 10 patients, with 2 cases recognized by next-generation sequencing, highlighting potential benefits of these assays.

Timely diagnosis of microorganisms in blood cultures is necessary to optimize therapy. Although blood culture media and systems have evolved for decades, the standard interval for incubation prior to being discarded as negative has remained 5 days. Here, we evaluated the optimal incubation time for the BacT/Alert Virtuo blood culture detection system (bioMérieux) using FA Plus (aerobic) and FN Plus (anaerobic) resin culture bottles in routine clinical use., Timely diagnosis of microorganisms in blood cultures is necessary to optimize therapy. Although blood culture media and systems have evolved for decades, the standard interval for incubation prior to being discarded as negative has remained 5 days. Here, we evaluated the optimal incubation time for the BacT/Alert Virtuo blood culture detection system (bioMérieux) using FA Plus (aerobic) and FN Plus (anaerobic) resin culture bottles in routine clinical use. Following institutional review board (IRB) approval, a retrospective review evaluated the outcomes of 158,710 bottles collected between November 2018 and October 2019. The number of positive blood bottles was 13,592 (8.6%); 99% of positive aerobic and anaerobic bottles flagged positive by 91.5 and 108 h, respectively. The mean (median) times to positivity were 18.4 h (15.6 h) for Staphylococcus aureus, 12.3 h (9.5 h) for Escherichia coli, 22.2 h (15.9 h) for Pseudomonas aeruginosa, and 48.9 h (42.9 h) for Candida spp. Only 175 bottles (0.1% of all bottles) flagged positive after 4 days of incubation; 89 (51%) of these bottles grew Cutibacterium (Propionibacterium) species. Chart review of blood cultures positive after 4 days (96 h) rarely had a clinical impact and sometimes had a negative impact on patient care. Finally, a seeded study of the HACEK group (i.e., Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella), historically associated with delayed blood culture positivity, demonstrated no benefit to extended incubation beyond 4 days. Collectively, these findings demonstrated that a 4-day incubation time was sufficient for the Virtuo system and media. Implementation of the 4-day incubation time could enhance clinically relevant results by reducing recovery of contaminants and finalizing blood cultures 1 day earlier.

A 49-year-old man with a 37.5 pack-year smoking history presented with a suspected neoplasm of the right lung following the discovery of a metabolically active mass on positron emission tomography-CT imaging. The patient, who demonstrated poor oral hygiene, had a history of irregular problem-oriented dental visitation. Having excluded malignancy through histologic investigations, Aggregatibacter actinomycetemcomitans—a well-established periodontal pathogen—was subsequently cultured from his pulmonary aspirate. The patient was therefore managed with systemic antimicrobials and adjunctive dental extractions to eliminate the likely source of infection, whereafter the mass resolved without complication. This case corroborates previous reports of extraoral isolation of A. actinomycetemcomitans, which may mimic cancer clinically and radiographically. While a definitive causative link between untreated periodontitis and systemic infection remains to be elucidated, such cases present a compelling argument in favour of promoting oral health to prevent systemic disease.

Infective endocarditis (IE) caused by bacteria within Haemophilus (excluding Haemophilus influenzae), Aggregatibacter, Cardiobacterium, Eikenella and Kingella (HACEK) is rare. This study aimed to describe clinical features of IE caused by HACEK genera in comparison with IE due to other pathogens. Cases of IE due to HACEK were identified through the Swedish Registry of Infective Endocarditis (SRIE). Clinical characteristics of IE cases caused by HACEK were compared with cases of IE due to other pathogens reported to the same registry. Ninety-six patients with IE caused by HACEK were identified, and this corresponds to 1.8% of all IE cases. Eighty-three cases were definite endocarditis, and the mortality rate was 2%. The median age was 63 years, which was lower compared to patients with IE caused by other pathogens (66, 70 and 73 years respectively, p ≤ 0.01). Patients with IE caused by Haemophilus were younger compared to patients with IE due to Aggregatibacter (47 vs 67 years, p ≤ 0.001). Patients with IE due to HACEK exhibited longer duration from onset of symptoms to hospitalization and had more prosthetic valve endocarditis compared to patients with IE due to Staphylococcus aureus (10 vs 2 days, p ≤ 0.001, and 35 vs 14%, p ≤ 0.001). This is, to date, the largest study on IE due to HACEK. Aggregatibacter was the most common cause of IE within the group. The condition has a subacute onset and often strikes in patients with prosthetic valves, and the mortality rate is relatively low.

Background Transmural healing (TH) is associated with better long-term outcomes in Crohn disease (CD), whereas pretreatment ileal gene signatures encoding myeloid inflammatory responses and extracellular matrix production are associated with stricturing. We aimed to develop a predictive model for ileal TH and to identify ileal genes and microbes associated with baseline luminal narrowing (LN), a precursor to strictures. Materials and Methods Baseline small bowel imaging obtained in the RISK pediatric CD cohort study was graded for LN. Ileal gene expression was determined by RNASeq, and the ileal microbial community composition was characterized using 16S rRNA amplicon sequencing. Clinical, demographic, radiologic, and genomic variables were tested for association with baseline LN and future TH. Results After controlling for ileal location, baseline ileal LN (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.8), increasing serum albumin (OR, 4; 95% CI, 1.3-12.3), and anti-Saccharomyces cerevisiae antibodies IgG serology (OR, 0.97; 95% CI, 0.95-1) were associated with subsequent TH. A multivariable regression model including these factors had excellent discriminant power for TH (area under the curve, 0.86; positive predictive value, 80%; negative predictive value, 87%). Patients with baseline LN exhibited increased Enterobacteriaceae and inflammatory and extracellular matrix gene signatures, coupled with reduced levels of butyrate-producing commensals and a respiratory electron transport gene signature. Taxa including Lachnospiraceae and the genus Roseburia were associated with increased respiratory and decreased inflammatory gene signatures, and Aggregatibacter and Blautia bacteria were associated with reduced extracellular matrix gene expression. Conclusions Pediatric patients with CD with LN at diagnosis are less likely to achieve TH. The association between specific microbiota, wound healing gene programs, and LN may suggest future therapeutic targets.

BackgroundMicrobiome research has focused on populations that are predominantly of European descent, and from narrow demographics that do not capture the socio-economic and lifestyle differences which impact human health. This limits our understanding of human-host microbiota interactions in their broadest sense. Here we examined the airway microbiology of the Orang Asli, the indigenous peoples of Malaysia. In addition to exploring the carriage and antimicrobial resistance of important respiratory pathobionts, we also present the first investigation of the nasal microbiomes of these indigenous peoples, in addition to their oral microbiomes.ResultsA total of 130 participants were recruited to the study from Kampung Sungai Pergam and Kampung Berua, both sites in the north-eastern state of Terengganu in Peninsular Malaysia. High levels ofStaphylococcus aureuscarriage were observed, particularly in the 18-65 age group (n=17/36; 47.2% 95%CI: 30.9-63.5). The highest carriage of pneumococci was in the p= 0.001). Hierarchical clustering of Bray-Curtis dissimilarity scores revealed six microbiome types. The largest cluster (n=28; 35.4%) had a marked abundance ofCorynebacterium.Others comprisedCorynebacteriumwithDolosigranulum, two clusters were definable by the presence ofMoraxella, one with and the other withoutHaemophilus, a small grouping ofDelftia/ Ochrobactumprofiles and one withStreptococcus. NoStaphylococcusprofiles were observed. In the oral microbiomesStreptococcus, NeisseriaandHaemophiluswere dominant. Lower levels ofPrevotella, Rothia, Porphyromonas, VeillonellaandAggregatibacterwere also among the eight most observed genera.ConclusionsWe present the first study of Orang Asli airway microbiomes and pathobiont microbiology. Key findings include the prevalence of pneumococcal serotypes that would be covered by pneumococcal conjugate vaccines if introduced into a Malaysian national immunisation schedule, and the high level ofS. aureuscarriage. The dominance ofCorynebacteriumin the airway microbiomes is particularly intriguing given its’ consideration as a potentially protective commensal with respect to acute infection and respiratory health.

Background/purpose This study aimed to investigate the clinical characteristics and outcomes of bacteremia caused by Haemophilus and Aggregatibacter species in patients who were treated at a medical center between 2006 and 2018. Methods Haemophilus and Aggregatibacter isolates were identified up to the species level using Bruker Biotyper MALDI-TOF analysis and ancillary 16S rRNA gene sequencing analysis (in case of ambiguity). Clinical characteristics and outcomes of patients with bacteremia caused by these organisms were evaluated. Results Sixty-five Haemophilus and Aggregatibacter species isolates causing bacteremia were identified from nonduplicated patients, including 51 (78.5%) Haemophilus influenzae, 6 (9.2%) Haemophilus parainfluenzae, 1 (1.5%) Haemophilus haemolyticus, 3 (4.6%) A. aphrophilus, and 4 (6.2%) A. segnis. Hospital mortality was observed in 18 (28.1%) of 64 patients with bacteremia caused by Haemophilus (n = 57) and Aggregatibacter species (n = 7). The majority of patients with bacteremia had community-acquired disease with low severity. The average Sequential Organ Failure Assessment (SOFA) score was low (4.4 ± 4.7). But, a higher SOFA score (adjusted odds ratio 2.5, 95% confidence interval 1.22–5.12; P = 0.01) was an independent factor predicting poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia (n = 39). Conclusions The overall hospital mortality of 28.1% was observed among patients with bacteremia due to Haemophilus and Aggregatibacter species. A higher SOFA score was and independent predictor of poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia.

Introduction: Microbiome imbalance could be associated with the occurrence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Aims: To investigate the association between oral bacterial flora and the occurrence of AE-IPF. Methods: We have prospectively collected 142 patients with IPF, 264 healthy subjects and 31 patients with bacterial pneumonia. Baseline serum antibody levels against 17 bacteria were measured by ELISA. The correlations between these values and the occurrence of AE-IPF were evaluated. An imbalance in the number of bacteria was defined as the number of pathogenic bacteria minus that of inhibitory bacteria. Results: We have identified 7 bacteria potentially promoting AE-IPF (Porphyromonas type I, III, IV, V, Helicobacter, Campylobacter, and Tannerella) and 3 bacteria potentially inhibiting AE-IPF (Prevotella, Fusobacterium, and Aggregatibacter). The baseline number of pathogenic bacteria was increased in patients with AE-IPF compared with those without AE-IPF (4.1±2.3 vs 2.9±2.4, p=0.0049), whereas the number of inhibitory bacteria was decreased (1.1±1.1 vs 1.6±1.1, p=0.007). The imbalance in the number of bacteria was increased in patients with AE-IPF (3.0±2.2 vs 1.3±2.2, p Conclusions: The imbalance of pathogenic and inhibitory bacteria was associated with the occurrence of AE-IPF.

Introduction: COPD is related to decline in lung function and microbiome dysbiosis. The relationship between airway bacterial profile with respiratory function and bronchial brush transcriptome in COPD is uncertain. Aim: We sought to investigate the association of COPD bronchial brush microbiome with lung function and bronchial gene expression. Method: Subjects with mild to moderate COPD (n=339) and healthy control individuals (n=207) were recruited as part of the EvA consortium. Spirometry was used to assess the Subjects’ lung function. microbial profile and gene expression from bronchscopic bronchial brush samples were obtained through 16S rRNA gene sequencing and RNAseq respectively. Results: A regression analysis of the postbronchodilator FEV1 % predicted versus bacterial genera abundance revealed Aggregatibacter genus had a significant negative association with respiratory function in COPD samples (r = -5.35; Adjusted p=2.30E-04) and also combined samples from COPD and healthy individuals (r = -2.81; Adjusted p=3.15E-02). Regression analysis of Aggregatibacter abundance versus lung transcriptome revealed four genes (CCL20, PTGS2, IL1B and CF3) with significant positive associations in combined COPD and control samples, however no significant associations were observed between them in either COPD or control samples alone. These genes were involved in IL-17 signalling, TNF signalling, cytokine-cytokine receptor interaction and NF-kappa B signalling pathways. Conclusion: With reduction in the respiratory function, the lung microbiome is associated with increase abundance of Aggregatibacter and up-regulation of pro-inflammatory genes involving in host inflammatory response pathways.

Recent evidence has demonstrated that salivary molecules, as well as bacterial populations, can be perturbed by several pathological conditions, including neuro-psychiatric diseases. This relationship between brain functionality and saliva composition could be exploited to unveil new pathological mechanisms of elusive diseases, such as Autistic Spectrum Disorder (ASD). We performed a combined approach of miRNA expression profiling by NanoString technology, followed by validation experiments in qPCR, and 16S rRNA microbiome analysis on saliva from 53 ASD and 27 neurologically unaffected control (NUC) children. MiR-29a-3p and miR-141-3p were upregulated, while miR-16-5p, let-7b-5p, and miR-451a were downregulated in ASD compared to NUCs. Microbiome analysis on the same subjects revealed that Rothia, Filifactor, Actinobacillus, Weeksellaceae, Ralstonia, Pasteurellaceae, and Aggregatibacter increased their abundance in ASD patients, while Tannerella, Moryella and TM7-3 decreased. Variations of both miRNAs and microbes were statistically associated to different neuropsychological scores related to anomalies in social interaction and communication. Among miRNA/bacteria associations, the most relevant was the negative correlation between salivary miR-141-3p expression and Tannerella abundance. MiRNA and microbiome dysregulations found in the saliva of ASD children are potentially associated with cognitive impairments of the subjects. Furthermore, a potential cross-talking between circulating miRNAs and resident bacteria could occur in saliva of ASD.

Background and Aim: Reflux Esophagitis (RE) is caused by a variety of factors including anatomical and functional alterations involved in the pathogenesis. Oral microbiota is influenced by many factors such as heredity, nutrition, environments and host conditions, but little is known about relationship between oral microbiota and RE. The aim of this study was to explore whether the oral microbiota is changed in patients with RE. Methods: To clarify this correlation, fresh saliva samples from all subjects were collected and then oral microorganism diversity was analysed in 55 patients with RE and 51 controls via hypervariable tag sequencing and analyzing the V3–V4 region of the 16S rDNA gene. Results: There was no difference found in oral microbial diversity between RE patients and healthy controls by Shannon diversity index (p=0.60) and Simpson diversity index (p= 0.38). The abundance of Proteobacteria was lower, but Bacteroidetes was higher in patients with RE at the phylum level. At the genus level the abundances of Prevotella, Veillonella, Megasphaera, Peptostreptococcus, Atopobium, Oribacterium, Eubacterium, and Lachnoanaerobaculum were increased, while Neisseria, Streptococcus, Rothia, Granulicatella, Gemella, Aggregatibacter, Treponema, Campylobacter, Filifactor, Corynebacterium, and Lactivibrio were decreased in RE patients than the controls. Conclusions: Our study suggested oral microbial dysbiosis in patients with RE, and identified bacterial species with potential biomarker significance. Further studies are required to understand role of oral microbial dysbiosis in the pathogenesis of RE.

Empyema necessitans is a relatively rare clinical entity in which the empyema extends through the parietal pleura into the adjacent soft tissue and musculature of the chest wall. It usually occurs due to inadequate treatment of a primary lung infection. Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans is a facultative anaerobic gram-negative coccobacillus that is part of the normal oral flora. Infections due to this organism usually result from aspiration in conjunction with dental disease or trauma to the oral mucosa resulting in pneumonia or empyema. It often coinfects with Actinomyces and is known to cause empyema necessitans. Cases of monomicrobial empyema necessitans due to Aggregatibacter actinomycetemcomitans in adults have rarely been reported with four such publications found on review of the literature. We present a patient with severe periodontitis who developed empyema necessitans due to Aggregatibacter actinomycetemcomitans likely from aspiration complicated by pyomyositis of the right triceps brachii and a left posterior thigh abscess.

This study aimed to characterize the microbial community and metabolic profiles in generalized aggressive periodontitis (AgP) using 16S ribosomal RNA (rRNA) gene high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS). A total of 146 subgingival plaque samples and 50 gingival crevicular fluid (GCF) samples were collected from 24 patients with AgP and 10 periodontally healthy subjects (PH). Striking differences were observed in subgingival microbiome and GCF metabolomics between patients with AgP and PH, but not between samples with different probing depths (PDs). Metabolomics analysis combined with enrichment analysis showed that periodontitis significantly altered the concentration of compounds associated with biosynthesis of amino acids (e.g., alanine, leucine, isoleucine, and valine), galactose metabolism (e.g., myo-inositol, galactose, glucose, and hexitol), and pyrimidine metabolism (e.g., uracil, uridine, beta alanine, and thymine). Correlation analysis showed that the genera with significant difference between AgP and PH were usually significantly correlated with more metabolites, such asAggregatibacter,Rothia,Peptostreptococcaceae_[XI][G-5], andBacteroidaceae_[G-1]. While glucose and oxoproline had the most significant correlations with microorganisms. Our results revealed distinct microbial communities and metabolic profiles between AgP and PH. The significant correlation between microbial taxa and metabolites suggested the possible mechanisms for periodontitis. Our results also provided effective approaches for detecting periodontal disease and managing periodontitis.

The objective was to describe the epidemiology, bacteriology, clinical presentation, risk factors for endocarditis (IE), diagnostic workup, and outcome of patients with bacteremia caused by the non-influenzae Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella genera (HACEK). A retrospective population-based cohort of patients with bacteremia collected from 2012 to 2017 was identified. Clinical data from identified patients were collected from medical records to classify patients, calculate incidences, analyze risk factors of IE, and describe the management and outcome of the cohort. A total of 118 episodes of HACEK bacteremia were identified, of which 27 were definite IE. The incidence of HACEK bacteremia was 5.2 and of HACEK IE 1.2 episodes per 1,000,000 inhabitants per year. Other focal infections were identified in 55 of 118 of the episodes, most commonly within the abdomen (26 episodes). The propensity to cause IE ranged from 62 in Aggregatibacter actinomycetemcomitans to 6% in Eikenella. Risk factors for IE were cardiac implantable electronical device, predisposing cardiac conditions, community acquisition, long duration of symptoms, multiple positive blood cultures, fever, heart murmur, embolization, and unknown origin of infection. The scoring system DENOVA developed to predict IE in bacteremia with Enterococcus faecalis also had a high sensitivity and specificity for predicting IE in HACEK bacteremia. The 30-day mortality was 4% in IE and 15% in non-IE bacteremia, and only one case of relapse was found. IE is common in bacteremia with Aggregatibacter, Cardiobacterium, and Kingella but relatively rare in Haemophilus and Eikenella. Treatment failures are very rare, and DENOVA can be used to evaluate the need for transesophageal echocardiography.

Highlights • actinomycetemcomitans causes periodontitis, endocarditis and soft tissue abscess. • First case of A. actinomycetemcomitans diaphragmatic infection without lung injury. • Hematogenous spread of A. actinomycetemcomitans from oral mucosa to thorax. • Color is not necessary for the figure., A 52-year-old man was evaluated in our outpatient facility because of a thoracic mass for one month. A needle biopsy of the chest mass was performed and microbiological culture showed growth of Aggregatibacter actinomycetemcomitans. Three months after starting antimicrobial therapy, acute phase reactants normalized, and chest CT showed a progressive reduction in the size of the phlegmon. To our knowledge, we report the first case of A. actinomycetemcomitans diaphragmatic and chest wall infection without pulmonary involvement. This supports the theory of hematogenous spread of the germ from oral mucosa to produce thoracic lesions.

To assess the influence of periodontal disease on cerebral hemorrhage and its clinical course, we examined the association of the serum IgG titer of periodontal pathogens with hemorrhage growth and 3-month outcome. We consecutively enrolled 115 patients with acute cerebral hemorrhage (44 females, aged 71.3 ± 13.1 years) and used ELISA to evaluate the serum IgG titers of 9 periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter (A.) actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium (F.) nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, and Eikenella corrodens. Significant hematoma growth was defined as an increase in the volume of >33% or an absolute increase in the volume of >12.5 mL. A poor outcome was defined as a 3 or higher on the modified Rankin Scale. We observed hemorrhage growth in 13 patients (11.3%). Multivariate analysis revealed that increased IgG titers of A. actinomycetemcomitans independently predicted the elevated hemorrhage growth (odds ratio 5.26, 95% confidence interval 1.52-18.25, p = 0.01). Notably, augmented IgG titers of F. nucleatum but not A. actinomycetemcomitans led to a poorer 3-month outcome (odds ratio 7.86, 95% confidence interval 1.08-57.08, p = 0.04). Thus, we demonstrate that elevated serum IgG titers of A. actinomycetemcomitans are an independent factor for predicting cerebral hemorrhage growth and that high serum IgG titers of F. nucleatum may predict a poor outcome in patients with this disease. Together, these novel data reveal how systemic periodontal pathogens may affect stroke patients, and, should, therefore, be taken into consideration in the management and treatment of these individuals.

Background and objective Periodontitis is an oral chronic inflammatory disease caused by dental plaque. It is comorbid with numerous systemic diseases and associated with several predisposing factors, such as chronic kidney disease (CKD). Peritoneal dialysis is one of the ultimate treatments for patients with severe CKD. However, peritoneal dialysis patients with periodontitis often will be accompanied with more poor oral hygiene and periodontal clinical indexes. This study aimed to compare the microbial flora of periodontitis patients with or without peritoneal dialysis. Methods Sixteen peritoneal dialysis patients with periodontitis (P group) and 16 patients with periodontitis only (C group) were selected. Subgingival plaque samples of them were processed for bioinformatics analysis by 16S rDNA gene sequencing. Results The diversity indices and species richness in the P group were insignificantly higher than that in the C group (P > 0.05). The two groups exhibited different microbial community structure. At Genus level, Prevotellaceae, Selenomonas, Aggregatibacter, Anaeroglobus, TM7_[G-5], and Centipeda were significantly enriched in the P group than those in the C group. Conclusions This study demonstrated that specific microbes enriched in the subgingival flora of peritoneal dialysis patients with periodontitis.

The use of next generation sequencing and bioinformatics has revealed the complexity and richness of the human oral microbiota. While some species are well known for their periodontal pathogenicity, the molecular-based approaches for bacterial identification have raised awareness about new putative periodontal pathogens. Although they are found increased in case of periodontitis, there is currently a lack of data on their interrelationship with the periodontal measures. We processed the sequencing data of the subgingival microbiota of 75 patients with hemochromatosis and chronic periodontitis in order to characterize the well-described and newly identified subgingival periodontal pathogens. We used correlation tests and statistical models to assess the association between the periodontal pathogens and mean pocket depth, and to determine the most relevant bacterial biomarkers of periodontitis severity. Based on correlation test results, nine taxa were selected and included in the statistical models. The multiple linear regression models adjusted for systemic and periodontal clinical variables showed that mean pocket depth was negatively associated with Aggregatibacter and Rothia, and positively associated with Porphyromonas. Furthermore, a bacterial ratio that was previously described as a signature of dysbiosis in periodontitis (%Porphyromonas+%Treponema+%Tannerella)/(%Rothia+%Corynebacterium) was the most significant predictor. In this specific population, we found that the best model in predicting the mean pocket depth was microbial dysbiosis using the dysbiosis ratio taxa formula. While further studies are needed to assess the validity of these results on the general population, such a dysbiosis ratio could be used in the future to monitor the subgingival microbiota.

Background The relationship between oral microbiota and IE (infective endocarditis) is well established. Opportunistic pathogens in normal oral flora enter the bloodstream through daily oral cleaning or invasive dental procedures, leading to the occurrence of infective endocarditis. An in vitro iron-deficient condition leads to a drastic community shift in oral microbiota with increasing proportions of taxa related to infective endocarditis. To investigate the relationship among insufficient iron supply, oral microbiota and the risk of IE and to conduct a population amplification study, iron-deficiency anaemia is used as an in vivo model. Methods This cross-sectional study enrolled 24 primary iron-deficiency anemia (IDA) patients from 2015.6 to 2016.6 from the hematology department of West China Hospital, Sichuan University, and 24 healthy controls. High-throughput sequencing compared the dental plaque microbiota of 24 IDA (iron-deficiency anaemia) patients and 24 healthy controls. Results Sequences were classified into 12 phyla, 28 classes, 50 orders, 161 genera and 497 OTUs (the IDA and control groups shared the same 384 OTUs). Iron deficiency leads to lower internal diversity in the oral flora. The abundances of genera Corynebacterium, Neisseria, Cardiobacterium, Capnocytophaga, and Aggregatibacter were significantly higher in healthy controls, while genera Lactococcus, Enterococcus, Lactobacillus, Pseudomonas and Moraxella showed higher proportions in the IDA group (P P Conclusions Without an increase of oral streptococci, the main pathogen of IE, it is difficult to determine whether IDA can increase the risk of IE. However, the iron-deficient condition did lead to changes in the oral microbiota community structure. The genera that showed higher proportions in the IDA group were frequently reported as antibiotic-resistant. As antibiotics are commonly recommended to prevent IE before dental procedures, this study offers new ideas of personalized prevention of IE.

Backgroud/purpose: Aggregatibacter actinomycetemcomitans has emerged as one of the aetiological agents in periodontal disease. Although Type IV secretion systems (T4SSs) are widely distributed in many bacteria, the genetic features and distribution of T4SSs in A. actinomycetemcomitans remain unclear. In this study, we investigated the prevalence of A. actinomycetemcomitans serotypes and their T4SSs in a Taiwanese population. Methods: A comparative analysis of 20 A. actinomycetemcomitans genomes and their T4SSs deposited in GenBank was performed. One hundred subjects, including 20 periodontitis and 80 normal subjects, were enrolled and PCR identification of A. actinomycetemcomitans serotypes and T4SS genes were performed. Results: Of 100 subjects, serotypes C (22%) and E (11%) were most common. In addition, T4SSs were distributed in all of the serotypes. The prevalence of T4SSs and their location in plasmids in periodontitis subjects were 1.28–2 fold higher but not significantly different compared to normal subjects. Of 20 A. actinomycetemcomitans genomes, only ten with complete T4SS modules could be detected, which was highly correlated with localized aggressive periodontitis (p

Background/Purpose: Subgingival microorganisms are potentially associated with periodontal diseases. However, the correlation between the variance in the periodontal microbiome and the prevalence and severity of periodontitis remains unclear. The aim of this study was to determine the subgingival microbiota in Taiwanese individuals with severe chronic periodontitis (SP). Methods: The composition of the subgingival microbiota in healthy and diseased individuals was compared using a 16S rRNA metagenomic approach and quantitative polymerase chain reaction (qPCR). A total of 20 samples, including 10 from healthy individuals and 10 from SP patients, were analyzed. Results: We found high microbial diversity, with an average of 774 classified phylotypes per sample and a total of six bacterial phyla across all samples. Cluster analysis by principal component analysis and heat map showed that the bacterial communities were different in the two groups. Streptococcus dominated across all the healthy samples, whereas Prevotella, Porphyromonas, and Treponema were highly abundant across all diseased samples. At least 13 bacterial genera were conserved among all the samples. Only eight genera, including Lautropia, Parvimonas, Actinomyces, Capnocytophaga, Paludibacter, Streptococcus, Haemophilus, and Corynebacterium, were significantly enriched in the healthy group, and six genera, including Porphyromonas, Treponema, Tannerella, Aggregatibacter, Peptostreptococcus, and Filifactor, were significantly enriched in the diseased group. Furthermore, a trend of abundance of bacteria at the species level measured by qPCR in all samples was consistent with the 16S rRNA metagenomics results. Conclusion: This study is the first in Taiwan to provide a picture of the microbiome in SP via 16S rRNA metagenomics. Keywords: 16S rRNA metagenomics, severe chronic periodontitis

AIM The study aims to assess the Mentha piperita leaf extract's effectiveness against oral pathogens. MATERIALS AND METHODS The leaf extract of M. piperita was prepared using cold water method. The three microbial strains, i.e., Streptococcus mutans, Aggregatibacter actinomycetem-comitans, and Candida albicans were used as microbiological materials. Chlorhexidine 0.2% was used as positive control. The digital caliper was used to measure the zone of inhibition to know the antimicrobial activity at 24 and 48 hours. To compare the activity within and between the different microbial strains, one-way analysis of variance (ANOVA) was used. To analyze the data, Statistical Package for the Social Sciences (SPSS) software version of 21.0 was used. The p-value ≤0.05 was considered as statistically significant. RESULTS Maximum inhibition zone was seen in both M. piperita extracts and 0.2% chlorhexidine with S. mutans at 24 and 48 hours, followed by A. actinomycetemcomitans, and C. albi-cans respectively. The statistical analysis ANOVA reveals the statistically significant association of M. piperita extracts with p-value

Objective The possibility of infectious trigger at the gingival site in rheumatoid arthritis (RA) was reported in previous studies. The aim of our study is to determine the organisms causing periodontitis (PD) in a cohort of Egyptian patients with RA and their relation to serum and gingival anticitrullinated peptide protein antibodies (ACPA) level and other disease parameters. Patients and methods A prospective cohort study was conducted on 100 consecutive Egyptian patients with RA. Disease activity was assessed by applying disease activity score-28, and functional status was measured using health assessment questionnaire. Dental examination, serum rheumatoid factor, ACPA in serum and gingival crevicular fluid (GCF), and radiograph of the hands were done for all patients. GCF culture was performed for all cases with PD for Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), and Prevotella intermedia (Pi). Results Of the 100 patients, 66 patients had PD; of them, GCF culture was performed, and Pg, Aa, and Pi were found in 60.6, 15.2, and 30.3% of patients with RA with PD, respectively. Gingival ACPA showed significant higher level with Pg than Pi cases (P=0.047). No statistically significant difference was detected on comparing Pg with Aa or Aa with Pi. Aa-positive cases were associated with significantly higher level of C-reactive protein than Pi-positive cases (P=0.029), whereas no statistical significant difference was detected between Pg- and Aa-positive or Pi-positive cases. Conclusion Our findings support the relationship between PD and infectious trigger at the gingival site and RA. Pg is the most prevalent periodontal microbiota in our cohort of patients with RA with PD that is associated with significant higher level of gingival ACPA. None of the detected organisms correlated with the degree of RA activity or other disease parameters, apart from significantly higher C-reactive protein level with Aa.

Background: Subgingival niche is one biofilm habitat containing rich microbiota, which plays an active role in maintaining the health of periodontal tissue and determining host response. As such, a study of changing subgingival biofilms is important for understanding the effect of a systemic condition. In this study, we compared the occurrence of six bacteria cohabiting in the subgingival area of periodontitis subjects, with (DP, n = 8) and without (NDP, n = 4) diabetes. Methods: The six genus and species of targeted bacteria were confirmed by 16S rRNA amplicon sequencing on MinION nanopore platform. Descriptive statistic was used to describe the obtained data. Results: We found that the six genus and species of targeted bacteria were detected but in different quantities in either group's periodontal pocket. Our data showed that Tannerella forsythia was the most abundant species in subgingival biofilms of the DP group of the red complex bacteria. In contrast, Aggregatibacter sp., which belongs to the phylum of proteobacteria, was present at a relatively lower level. In contrast, Fusobacterium sp., which belongs to orange complex bacteria, showed relative similarities in subgingival biofilms of both groups tested, while Veillonella sp., were abundant in the DP groups. Conclusions: Our data show that the diversity of classic periodontopathogens increased in the subgingival niche of periodontitis subjects with diabetes. It is the first study in Indonesia to apply MinION-based, full-length 16S rRNA amplicon sequencing in periodontitis patients with and without diabetes.

// Pranab K. Mukherjee 1,* , Hannah Wang 2, 3, * , Mauricio Retuerto 1 , Huan Zhang 2, 3 , Brian Burkey 4, 7 , Mahmoud A. Ghannoum 1, 7, 8 and Charis Eng 2, 3, 4, 6, 8 1 Center for Medical Mycology, Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA 2 Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA 3 Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA 4 Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA 5 Section of Head and Neck Surgery and Oncology, Head and Neck Institute, Cleveland Clinic, Cleveland, OH, USA 6 Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA 7 Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA 8 Germline High Risk Cancer Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA * Contributed equally to the work and should be viewed as joint first authors Correspondence to: Charis Eng, email: engc@ccf.org Mahmoud A. Ghannoum, email: mag3@case.edu Keywords: microbiome; metagenomics; head and neck squamous cell carcinoma; lingual carcinomas Received: June 08, 2017 Accepted: September 08, 2017 Published: October 19, 2017 ABSTRACT Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P

BackgroundInfective endocarditis (IE) caused by Abiotrophia (ABI) and Granulicatella (GRA) species is poorly studied. This work aims to describe and compare the main features of ABI and GRA IE.MethodsWe performed a retrospective study of 12 IE institutional cases of GRA or ABI and of 64 cases published in the literature (overall, 38 ABI and 38 GRA IE cases).ResultsABI/GRA IE represented 1.51% of IE cases in our institution between 2000 and 2015, compared to 0.88% of HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)–related IE and 16.62% of Viridans group streptococci (VGS) IE. Institutional ABI/GRA IE case characteristics were comparable to that of VGS, but periannular complications were more frequent (P = .008). Congenital heart disease was reported in 4 (10.5%) ABI and in 11 (28.9%) GRA cases (P = .04). Mitral valve was more frequently involved in ABI than in GRA (P < .001). Patient sex, prosthetic IE, aortic involvement, penicillin susceptibility, and surgical treatment were comparable between the genera. New-onset heart failure was the most frequent complication without genera differences (P = .21). Five (13.2%) ABI patients and 2 (5.3%) GRA patients died (P = .23). Factors associated with higher mortality were age (P = .02) and new-onset heart failure (P = .02). The genus (GRA vs ABI) was not associated with higher mortality (P = .23).ConclusionsGRA/ABI IE was more prevalent than HACEK IE and approximately one-tenth as prevalent as VGS; periannular complications were more frequent. GRA and ABI genera IE presented similar clinical features and outcomes. Overall mortality was low, and related to age and development of heart failure.

This study aimed to compare two nanofiber drug delivery systems that were prepared with an electrospun process and have the potential to serve as adjuvants for the treatment of periodontal disease. The first system was composed of polycaprolactone loaded with tetracycline (TCN) and the second was composed of polycaprolactone loaded with tetracycline/β-cyclodextrin (TCN:BCD). An antimicrobial diffusion test was performed for each of these sets of nanofibers with the microorganisms, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, both of which contribute to periodontal disease. In vitro release profiles were also obtained, and the nanofibers were characterized by thermal analysis, x-ray powder diffraction, infrared absorption spectroscopy, and scanning electron microscopy. Profiles of the TCN and TCN:BCD nanofibers showed that drug release occurred for up to 14days. However, the TCN:BCD nanofibers appeared to better protect and enhance the biological absorption of TCN due to the formation of a TCN:BCD inclusion complex.

Purpose: We aim to develop peptic nucleic acid (PNA) probes for the identification and localization of Aggregatibacter actinomycetemcomintans and Porphyromonas gingivalis in sub-gingival plaque and gingival biopsies by Fluorescence in situ Hybridization (FISH). Methods A PNA probe was designed for each microorganism. The PNA-FISH method was optimized to allow simultaneous hybridization of both microorganisms with their probe (PNA-FISH multiplex). After being tested on representative strains of P. gingivalis and A. actinomycetemcomitans, the PNA-FISH method was then adapted to detect microorganisms in the subgingival plaque and gingival samples, collected from patients with severe periodontitis. Results The best hybridization conditions were found to be 59 °C for 150 min for both probes (PgPNA1007 and AaPNA235). The in silico sensitivity and specificity was both 100% for PgPNA1007 probe and 100% and 99.9% for AaPNA235 probe, respectively. Results on clinical samples showed that the PNA-FISH method was able to detect and discriminate target bacteria in the mixed microbial population of the subgingival plaque and within periodontal tissues. Conclusion This investigation presents a new highly accurate method for P. gingivalis and A. actinomycetemcomitans detection and co-location in clinical samples, in just few hours. With this technique we were able to observe spatial distribution of these species within polymicrobial communities in the periodontal pockets and, for the first time with the FISH method, in the organized gingival tissue., The authors report no conflicts of interest. This work was financially supported by: Project POCI-01-0145-FEDER-006939 Laboratory for Process Engineering, Environment, Biotechnology and Energy—LEPABE funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI)—and by national funds through FCT—Fundação para a Ciência e a Tecnologia; PIC/IC/82815/2007, SFRH/BDE/51910/2012, SFRH/BD/82663/2011].

Background Oral microbiota is not only important for maintaining oral health but also plays a role in various oral diseases. However, studies regarding microbiome changes in oral lichen planus (OLP) are very limited. To the best of our knowledge, there has been only two studies investigating salivary microbiome changes in OLP. Therefore, the purpose of this study was to identify the characteristic microbial profile in the saliva of OLP patients, with or without erosive lesions, and compare that with recurrent aphthous ulcer (RAU), a common oral immunological disorder that also shows multiple erosive/ulcerative lesions. Whole saliva samples were collected from 20 patients with OLP (erosive E, n = 10 and non-erosive NE, n = 10), 10 patients with RAU (U) and 10 healthy controls (C). DNA was extracted from the saliva samples, and the 16S rDNA gene V4 hypervariable region was analyzed using Illumina sequencing. Results We obtained 4949 operational taxonomic units (OTUs) from the V4 region in all saliva samples. Community composition analysis showed a clear decreased relative abundance of genera Streptococcus and Sphingomonas in saliva from RAU patients when compared to the other three groups. Relative abundance of Lautropia and Gemella were higher in E group, whereas relative abundance of Haemophilus and Neisseria were higher in NE group when compared to C group. Abiotrophia and Oribacterium were higher in OLP (combining E and NE groups), while Eikenella and Aggregatibacter were lower when compared to C group. There was statistically significance in α-diversity between E and RAU groups(p g_Haemophilus might be the potential biomarker in NE group. Conclusions We found that salivary microbiome in erosive OLP was significantly different from that found in RAU; and these changes may be related to the underlying disease process rather than presence of ulcerative/erosive lesions clinically. In addition, our findings in bacterial relative abundance in OLP were significantly different from the previously reported findings, which points to the need for further research in salivary microbiome of OLP.

Eikenella corrodens is a facultatively anaerobic gram-negative rod bacterium in the oropharynx and respiratory tract. It is a member of HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, E. corrodens, and Kingella kingae) group commonly associated with endocarditis and craniofacial infections. It is usually susceptible to penicillin, second and third-generation cephalosporins, and carbapenem, but has variable susceptibility to first-generation cephalosporin. We herein provide a description of the first case of pediatric acute dacryocystitis caused by E. corrodens. The patient did not respond to oral cephalexin and required surgical drainage followed by intravenous cefotaxime. Also provided is a brief review of the current literature.

Introduction: Microbiome imbalance could be one of the risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). However, little is known about the role of the oral bacterial flora in AE-IPF. Aims: To investigate the significance of oral bacterial flora as a risk factor for AE-IPF. Methods: A total of 142 patients with IPF (77 German and 65 Japanese), 264 healthy subjects (164 German and 100 Japanese) and 31 Japanese patients with bacterial pneumonia were prospectively collected. Baseline serum levels of antibodies against 16 bacteria of the oral flora were measured by ELISA. The correlations between baseline serum levels of these antibodies and the incidence of AE-IPF were evaluated. Results: Baseline serum levels of Porphyromonas type III, IV, V, and Fusobacterium antibodies were significantly higher in the Japanese IPF patients compared with the other 4 groups (Japanese healthy, Japanese pneumonia, German healthy and German IPF). Baseline serum levels of several antibacterial antibodies (Porphyromonas type I, III, IV, V, Tannerella, and Campylobacter) were positively correlated with the occurrence of AE-IPF (AUC 0.554-0.608), whereas others (Aggregatibacter, Prevotella and Fusobcterium) were negatively correlated (AUC 0.400-0.441). Among them, the ratio of Tannerella to Aggregatibacter was significantly associated with the occurrence of AE-IPF (AUC 0.520-0.747, p=0.015). In the multivariate analysis, the ratio of Tannerella to Aggregatibacter > 0.72 and Japanese ethnicity were independent risk factors for AE-IPF (hazard ratio 2.23, p=0.03; 4.48, p=0.0002). Conclusions: An imbalance in the oral bacterial flora could be a risk factor for AE-IPF.

In this study, a next-generation sequencing strategy on 16S ribosomal RNA (16S rRNA) gene was employed to analyze 70 oral samples from 32 patients with throat cancer, nine patients with vocal cord polyp, and 29 healthy individuals (normal controls). Using this strategy, we demonstrated, for the first time, that the salivary microbiota of cancer patients were significantly different from those of patients with a polyp and healthy individuals. We observed that the beta diversity of the cancer group was divergent from both the normal and polyp groups, while alpha-diversity indices such as the Chao1 estimator (P = 8.1e-05), Simpson (P = 0.0045), and Shannon (P = 0.0071) were significantly reduced in cancer patients compared with patients containing a polyp and normal healthy individuals. Linear discriminant analysis (LDA) and Kruskal–Wallis test analyses and real-time quantitative polymerase chain reaction (qPCR) verification test revealed that the genera Aggregatibacter, Pseudomonas, Bacteroides, and Ruminiclostridium were significantly enriched in the throat cancer group compared with the vocal cord polyp and normal control groups (score value >2). Finally, diagnostic models based on putatively important constituent bacteria were constructed with 87.5% accuracy [area under the curve (AUC) = 0.875, 95% confidence interval (CI): 0.695–1]. In summary, in this study we characterized, for the first time, the oral microbiota of throat cancer patients without smoking history. We speculate that these results will help in the pathogenic mechanism and early diagnosis of throat cancer.

Objectives The pathogenesis of Graves’ disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China. Design and methods Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis and partial least squares-discriminant analysis (PLS-DA). Results The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P Conclusions The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.