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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.

Oral microbiome changes take place at the initiation of rheumatoid arthritis (RA); however, questions remain regarding the oral microbiome at pre-RA stages in individuals with clinically suspect arthralgia (CSA). Two cross-sectional cohorts were selected including 84 Tatarstan women (15 early-RA as compared to individuals with CSA ranging from CSA = 0 [

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...

Poor oral health has broad consequences that can be seen at personal as well as societal levels, especially in developing countries like India. We have limited information on the healthy oral cavity's inhabitant microorganisms that play a crucial role in overall oral health. In a comprehensive culture-independent approach, the bacterial composition of healthy human oral cavities was determined from a sub-population of northern India. During this study, 20 mouthwash-derived metagenomes were explored for identifying bacterial diversity using the 16S rRNA hypervariable V3 region with the MiSeq Illumina platform. On the taxonomy assignment of operational taxonomic units (OTUs), 20 assigned phyla and 162 genera were recovered among the participants. The mean relative abundance revealed that Streptococcus was the dominant genera among the participants. However, at inter-individual analysis, Neisseria and Haemophilus exhibited first-order dominance among five and three healthy individuals, respectively. Correlation studies indicate that Streptococcus shares a strong relationship with Rothia, Corynebacterium, Prevotella, and Veillonella, whereas it was negatively correlated with Neisseria, Aggregatibacter, Porphyromonas, and Fusobacteria like Gram-negative bacteria. Bacterial diversity showed insignificant differences at the level of age and gender within and between the participants. The results support several of the major findings of previous reports on the healthy oral microbiome of the Indian population, however, the present investigation further illustrates that demographic region leaves an impact on overall bacterial composition. The study will assist in a better understanding of the oral microbiome from region-specific Indian population that was otherwise highly under-represented.

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.

There has been considerable interest in the impact of short-chain fatty acids (SCFAs) on inflammatory effects related to the microbiome. Here, we present evidence that SCFAs may also be important in disease by providing an energy source or disease-associated cue for colonizing pathogens., Like the bacterial residents of the human gut, it is likely that many of the species in the human oral microbiota have evolved to better occupy and persist in their niche. Aggregatibacter actinomycetemcomitans (Aa) is both a common colonizer of the oral cavity and has been implicated in the pathogenesis of periodontal disease. Here, we present a whole-genome phylogenetic analysis of Aa isolates from humans and nonhuman primates that revealed an ancient origin for this species and a long history of association with the Catarrhini, the lineage that includes Old World monkeys (OWM) and humans. Further genomic analysis showed a strong association with the presence of a short-chain fatty acid (SCFA) catabolism locus (atoRDAEB) in many human isolates that was absent in almost all nonhuman OWM isolates. We show that this locus was likely acquired through horizontal gene transfer. When grown under conditions that are similar to those at the subgingival site of periodontitis (anaerobic, SCFA replete), Aa strains with atoRDAEB formed robust biofilms and showed upregulation of genes involved in virulence, colonization, and immune evasion. Both an isogenic deletion mutant and nonhuman primate isolates lacking the ato locus failed to grow in a robust biofilm under these conditions, but grew well under the carbohydrate-rich conditions similar to those found above the gumline. We propose that the acquisition of the ato locus was a key evolutionary step allowing Aa to utilize SCFAs, adapt, and modulate subgingival disease.

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.