Salivary Microbial Dysbiosis Is Associated With Peri-Implantitis: A Case-Control Study in a Brazilian Population

Background and ObjectivesThe aim of this study was to examine the salivary microbiome in healthy peri-implant sites and those with peri-implantitis.MethodsSaliva samples were collected from 21 participants with healthy peri-implant sites and 21 participants with peri-implantitis. The V4 hypervariable region of the 16S rRNA gene was sequenced using the Ion Torrent PGM System (Ion 318™ Chip v2 400). The NGS analysis and composition of the salivary microbiome were determined by taxonomy assignment. Downstream bioinformatic analyses were performed in QIIME (v 1.9.1).ResultsClinical differences according to peri-implant condition status were found. Alpha diversity metrics revealed that the bacterial communities of participants with healthy peri-implant sites tended to have a richer microbial composition than individuals with peri-implantitis. In terms of beta diversity, bleeding on probing (BoP) may influence the microbial diversity. However, no clear partitioning was noted between the salivary microbiome of volunteers with healthy peri-implant sites or volunteers with peri-implantitis. The highest relative abundance of Stenotrophomonas, Enterococcus and Leuconostoc genus, and Faecalibacterium prausnitzii, Haemophilus parainfluenzae, Prevotella copri, Bacteroides vulgatus, and Bacteroides stercoris bacterial species was found in participants with peri-implantitis when compared with those with healthy peri-implant sites.ConclusionDifferences in salivary microbiome composition were observed between patients with healthy peri-implant sites and those with peri-implantitis. BoP could affect the diversity (beta diversity) of the salivary microbiome.

Mechanisms underlying interactions between two abundant oral commensal bacteria

Complex polymicrobial biofilm communities are abundant in nature particularly in the human oral cavity where their composition and fitness can affect health. While the study of these communities during disease is essential and prevalent, little is known about interactions within the healthy plaque community. Here we describe interactions between two of the most abundant species in this healthy microbiome, Haemophilus parainfluenzae and Streptococcus mitis. We discovered that H. parainfluenzae typically exists adjacent to mitis group streptococci in vivo with which it is also positively correlated based on microbiome data. By comparing in vitro coculture data to ex vivo microscopy we revealed that this co-occurrence is density dependent and further influenced by H2O2 production. We discovered that H. parainfluenzae utilizes a more redundant, multifactorial response to H2O2 than related microorganisms and that this system’s integrity enhances streptococcal fitness. Our results indicate that mitis group streptococci are likely the in vivo source of NAD for H. parainfluenzae and also evoke patterns of carbon utilization in vitro for H. parainfluenzae similar to those observed in vivo. Our findings describe mechanistic interactions between two of the most abundant and prevalent members of healthy supragingival plaque that contribute to their in vivo survival.

1041. In vitro activity of tebipenem against a recent collection of fastidious organisms recovered from respiratory tract infections

Background Tebipenem is under development as an oral treatment option for complicated urinary tract infections and acute pyelonephritis. This study further evaluated the in vitro activity of tebipenem against various fastidious organisms recovered from community-acquired respiratory tract infections (CARTIs). Methods The study included a total of 2,476 fastidious organisms: Haemophilus influenzae (692 isolates, including fluoroquinolone-resistant, β-lactamase-positive, and β-lactamase-negative ampicillin-resistant [BLNAR]), Haemophilus parainfluenzae (30 isolates, including β-lactamase-positive and BLNAR), Moraxella catarrhalis (490 isolates), and Streptococcus pneumoniae (1,264 isolates, including penicillin-resistant). The isolates were collected primarily from CARTIs (90.8%) and pneumonia in hospitalized patients (PIHPs, 9.2%). Organisms were tested using reference broth microdilution methods in a central laboratory. Results Tebipenem had MIC90 values of 0.5 mg/L against H. influenzae and 1 mg/L against H. parainfluenzae isolates. All 18 BLNAR isolates from these two species were inhibited at ≤1 mg/L of tebipenem. The MIC90 values observed for ertapenem and meropenem was 0.25 mg/L for these organisms. Tebipenem displayed good activity against M. catarrhalis (MIC90, 0.03 mg/L). Tebipenem inhibited 100% of S. pneumoniae isolates at ≤1 mg/L. Tebipenem activity (MIC90, 0.12 mg/L) was 8-fold greater than ertapenem (MIC90, 1 mg/L) against S. pneumoniae isolates. Conclusion Tebipenem displayed potent activity against fastidious organisms causing respiratory tract infections. Greater than 99.7% of all Haemophilus isolates, including all BLNAR, were inhibited at ≤1 mg/L. All M. catarrhalis isolates were inhibited at ≤0.03 mg/L. Although tebipenem activity correlated with penicillin resistance, all S. pneumoniae isolates were inhibited at ≤1 mg/L. Tebipenem in vitro activity was greater than ertapenem when tested against S. pneumoniae isolates. This data supports the possible development of tebipenem as an oral option for combating CARTIs caused by these organisms. Table Disclosures S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L. Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

Oral Dysbiosis in Severe Forms of Periodontitis Is Associated With Gut Dysbiosis and Correlated With Salivary Inflammatory Mediators: A Preliminary Study

Inflammation is a driven force in modulating microbial communities, but little is known about the interplay between colonizing microorganisms and the immune response in periodontitis. Since local and systemic inflammation may play a whole role in disease, we aimed to evaluate the oral and fecal microbiome of patients with periodontitis and to correlate the oral microbiome data with levels of inflammatory mediator in saliva.Methods: Nine patients with periodontitis (P) in Stage 3/Grade B and nine age-matched non-affected controls (H) were evaluated. Microbial communities of oral biofilms (the supra and subgingival from affected and non-affected sites) and feces were determined by sequencing analysis of the 16SrRNA V3–V4 region. Salivary levels of 40 chemokines and cytokines were correlated with oral microbiome data.Results: Supragingival microbial communities of P differed from H (Pielou's evenness index, and Beta diversity, and weighted UniFrac), since relative abundance (RA) of Defluviitaleaceae, Desulfobulbaceae, Mycoplasmataceae, Peptostreococcales-Tissierellales, and Campylobacteraceae was higher in P, whereas Muribaculaceae and Streptococcaceae were more abundant in H. Subgingival non-affected sites of P did not differ from H, except for a lower abundance of Gemellaceae. The microbiome of affected periodontitis sites (PD ≥ 4 mm) clustered apart from the subgingival sites of H. Oral pathobionts was more abundant in sub and supragingival biofilms of P than H. Fecal samples of P were enriched with Acidaminococcus, Clostridium, Lactobacillus, Bifidobacterium, Megasphaera, and Romboutsia when compared to H. The salivary levels of interleukin 6 (IL-6) and inflammatory chemokines were positively correlated with the RA of several recognized and putative pathobionts, whereas the RA of beneficial species, such as Rothia aeria and Haemophilus parainfluenzae was negatively correlated with the levels of Chemokine C-C motif Ligand 2 (CCL2), which is considered protective. Dysbiosis in patients with periodontitis was not restricted to periodontal pockets but was also seen in the supragingival and subgingival non-affected sites and feces. Subgingival dysbiosis revealed microbial signatures characteristic of different immune profiles, suggesting a role for candidate pathogens and beneficial organisms in the inflammatory process of periodontitis.

Pathogen Metagenomics Reveals Distinct Lung Microbiota Signatures Between Bacteriologically Confirmed and Negative Tuberculosis Patients

Understanding the dynamics of lung microbiota in tuberculosis patients, especially those who cannot be confirmed bacteriologically in clinical practice, is imperative for accurate diagnosis and effective treatment. This study aims to characterize the distinct lung microbial features between bacteriologically confirmed and negative tuberculosis patients to understand the influence of microbiota on tuberculosis patients. We collected specimens of bronchoalveolar lavage fluid from 123 tuberculosis patients. Samples were subjected to metagenomic next-generation sequencing to reveal the lung microbial signatures. By combining conventional bacterial detection and metagenomic sequencing, 101/123 (82%) tuberculosis patients were bacteriologically confirmed. In addition to Mycobacterium tuberculosis, Staphylococcus aureus, Kluyveromyces lactis, and Pyricularia pennisetigena were also enriched in the bacteriological confirmation group. In contrast, Haemophilus parainfluenzae was enriched in the bacteriologically negative group. Besides, microbial interaction exhibits a different state between bacteriologically confirmed and negative tuberculosis patients. Mycobacterium tuberculosis was confirmed correlated with clinical characteristics such as albumin and chest cavities. Our study comprehensively demonstrates the correlation between unique features of lung microbial dynamics and the clinical characteristics of tuberculosis patients, suggesting the importance of studying the pulmonary microbiome in tuberculosis disease and providing new insights for future precision diagnosis and treatment.