SummaryA hallmark of infection with the gram-negative pathogen Porphyromonas gingivalis is the induction of a chronic inflammatory response. P. gingivalis induces a local chronic inflammatory ...response that results in oral inflammatory bone destruction, which manifests as periodontal disease. In addition to chronic inflammation at the initial site of infection, mounting evidence has accumulated supporting a role for P. gingivalis-mediated periodontal disease as a risk factor for several systemic diseases including, diabetes, preterm birth, stroke, and atherosclerotic cardiovascular disease. A growing number of in vitro studies have demonstrated that P. gingivalis infection stimulates cell activation commensurate with expected responses paralleling inflammatory atherosclerotic-type responses. Furthermore, various mouse models have been used to examine the ability of P. gingivalis to stimulate chronic inflammatory plaque accumulation and recent studies have pointed to a pivotal role for innate immune signaling via the Toll-like receptors in the chronic inflammation associated with P. gingivalis infection. In this review we discuss the pathogen and host cell specificity of these responses and discuss possible mechanisms by which this oral pathogen can induce and maintain a chronic state of inflammation at sites distant from oral infection.
Increasing evidence indicates that chronic inflammation due to periodontal disease is associated with progression of non-alcoholic fatty liver disease (NAFLD) caused by a Western diet. NAFLD has also ...been associated with oral infection with the etiological agent of periodontal disease,
.
oral infection has been shown to induce cardiometabolic disease features including hepatic lipid accumulation while also leading to dysbiosis of the gut microbiome. However, the impact of
infection on the gut microbiota of mice with diet-induced NAFLD and the potential for those changes to mediate NAFLD progression has yet to be determined. In the current study, we have demonstrated that
infection induced sustained alterations of the gut microbiota composition and predicted functions, which was associated with the promotion of NAFLD in steatotic mice. Reduced abundance of short-chain fatty acid-producing microbiota was observed after both acute and chronic
infection. Collectively, our findings demonstrate that
infection produces a persistent change in the gut microbiota composition and predicted functions that promotes steatosis and metabolic disease.
Purpose
The aim of this study was to evaluate the safety and efficacy of a new intragastric balloon (Elipse™ Balloon, Allurion Technologies, Natick, MA USA) not needing endoscopy.
Materials and ...Methods
The balloon was swallowed under fluoroscopy in 38 consecutive patients (F/M 28/10, mean age 46.4 ± 10.6 years, mean weight 109.7 ± 21.9 kg, and mean body mass index (BMI) 38.6 ± 6.7 kg/m
2
). After 4 months, the balloon spontaneously emptied and it was excreted through the digestive tract without upper endoscopy.
Results
There were no complications during balloon passage. After 16 weeks, the mean weight loss was 12.7 kg, mean percent excess weight loss was 26%, and mean BMI reduction was 4.2 kg/m
2
. Total body weight loss was 11.6%. There was a significant reduction in major co-morbidities related to metabolic syndrome: blood pressure (
p
< 0.02), waist circumference (
p
< 0.002), triglycerides (
p
< 0.0001), blood glucose (
p
< 0.001), and HOMA-IR index (
p
< 0.001). At the end of the treatment, 37 balloons were naturally excreted in the stool, and one balloon was endoscopically removed.
Conclusions
The results of this study on 38 consecutive patients demonstrate that the Elipse™ Balloon is safe, effective, and very well accepted by patients.
Abstract Objective Studies in humans support a role for the oral pathogen Porphyromonas gingivalis in the development of inflammatory atherosclerosis. The goal of this study was to determine if P. ...gingivalis infection accelerates inflammation and atherosclerosis in the innominate artery of mice, an artery which has been reported to exhibit many features of human atherosclerotic disease, including plaque rupture. Methods and results Apolipoprotein E-deficient (ApoE−/− ) mice were orally infected with P. gingivalis, and magnetic resonance imaging (MRI) was used to monitor the progression of atherosclerosis in live mice. P. gingivalis infected mice exhibited a statistically significant increase in atherosclerotic plaque in the innominate artery as compared to uninfected mice. Polarized light microscopy and immunohistochemistry revealed that the innominate arteries of infected mice had increased lipids, macrophages and T cells as compared to uninfected mice. Increases in plaque, total cholesterol esters and cholesterol monohydrate crystals, macrophages, and T cells were prevented by immunization with heat-killed P. gingivalis prior to pathogen exposure. Conclusions These are the first studies to demonstrate progression of inflammatory plaque accumulation in the innominate arteries by in vivo MRI analysis following pathogen exposure, and to document protection from plaque progression in the innominate artery via immunization.
Periodontal diseases are a group of diseases that lead to erosion of the hard and soft tissues of the periodontium, which, in severe cases, can result in tooth loss. Anecdotal clinical observations ...have suggested that poor oral health may be associated with poor systemic health; however, only recently have appropriate epidemiological studies been initiated, with defined clinical endpoints of periodontal disease, to address the association of periodontal disease with increased risk for cardiovascular and cerebrovascular disease. Although conflicting reports exist, these epidemiological studies support this connection. Paralleling these epidemiological studies, emerging basic scientific studies also support that infection may represent a risk factor for atherosclerosis. With P. gingivalis as a model pathogen, in vitro studies support that this organism can activate host innate immune responses associated with atherosclerosis, and in vivo studies demonstrate that this organism can accelerate atheroma deposition in animal models. In this review, we focus primarily on the basic scientific studies performed to date which support that infection with bacteria, most notably P. gingivalis, accelerates atherosclerosis. Furthermore, we attempt to bring together these studies to provide an up-to-date framework of emerging theories into the mechanisms underlying periodontal disease and increased risk for atherosclerosis, as well as identify intervention strategies to reduce the incidence of periodontal disease in humans, in an attempt to decrease risk for systemic complications of periodontal disease such as atherosclerotic cardiovascular disease.
The bacterium Neisseria gonorrhoeae (Ngo) is the main cause of the sexually transmitted infection gonorrhea. The global incidence of 87 million new Ngo infections each year, rising infection rates, ...and the emergence of Ngo strains that are resistant to all clinically recommended antibiotics have raised the specter of untreatable infections (M. Unemo, H. S. Seifert, E. W. Hook, III, S. Hawkes, et al., Nat Rev Dis Primers 5:79, 2019, https://doi.org/10.1038/s41572-019-0128-6). Given their abundance in symptomatic disease, neutrophils are central to both Ngo infection and consequent damage to host tissues. This article highlights present knowledge and the main open questions about Ngo-neutrophil interactions in immunity versus disease pathogenesis.
Recent advances in high-throughput RNA sequencing (RNA-seq) have enabled tremendous leaps forward in our understanding of bacterial transcriptomes. However, computational methods for analysis of ...bacterial transcriptome data have not kept pace with the large and growing data sets generated by RNA-seq technology. Here, we present new algorithms, specific to bacterial gene structures and transcriptomes, for analysis of RNA-seq data. The algorithms are implemented in an open source software system called Rockhopper that supports various stages of bacterial RNA-seq data analysis, including aligning sequencing reads to a genome, constructing transcriptome maps, quantifying transcript abundance, testing for differential gene expression, determining operon structures and visualizing results. We demonstrate the performance of Rockhopper using 2.1 billion sequenced reads from 75 RNA-seq experiments conducted with Escherichia coli, Neisseria gonorrhoeae, Salmonella enterica, Streptococcus pyogenes and Xenorhabdus nematophila. We find that the transcriptome maps generated by our algorithms are highly accurate when compared with focused experimental data from E. coli and N. gonorrhoeae, and we validate our system's ability to identify novel small RNAs, operons and transcription start sites. Our results suggest that Rockhopper can be used for efficient and accurate analysis of bacterial RNA-seq data, and that it can aid with elucidation of bacterial transcriptomes.
This study was conducted to determine the
activities of gentamicin alone and in combination with ceftriaxone, ertapenem, and azithromycin against multidrug-resistant (MDR) Neisseria gonorrhoeae ...isolates. A total of 407 clinical isolates from Nanjing, China, obtained in 2016 to 2017, had MICs determined for gentamicin using the agar dilution method. MDR status was ascribed to 97 strains that displayed decreased susceptibility or resistance to extended-spectrum cephalosporins (ESCs) (ceftriaxone MIC, ≥0.125 mg/liter and cefixime MIC, ≥0.25 mg/liter), plus resistance to at least two of the following antimicrobials: penicillin (MIC, ≥2 mg/liter), ciprofloxacin (MIC, ≥1 mg/liter), and azithromycin (MIC, ≥1 mg/liter). MDR strains underwent MIC determinations for antimicrobial combinations using the antimicrobial gradient epsilometer test (Etest). Results that ranged from synergy to antagonism were interpreted using the fractional inhibitory concentration (FICI). All 407 gonococcal isolates were susceptible to gentamicin; MICs ranged from 2 mg/liter to 16 mg/liter. Synergy was demonstrated in 16.5% (16/97), 27.8% (27/97), and 8.2% (8/97) of MDR strains when gentamicin was combined with ceftriaxone (geometric mean GM FICI, 0.747), ertapenem (GM FICI, 0.662), and azithromycin (GM FICI, 1.021), respectively. No antimicrobial antagonism was observed with any combination tested against MDR strains; overall, antimicrobial combinations were indifferent. The GM MICs of gentamicin were reduced by 2.63-, 3.80-, and 1.98-fold when tested in combination with ceftriaxone, ertapenem, and azithromycin, respectively. The GM MICs of the three additional antimicrobials individually were reduced by 3-, 2.57-, and 1.98-fold, respectively, when each was tested in combination with gentamicin. Gentamicin alone was effective
against N. gonorrhoeae, including MDR isolates. Combination testing of MDR strains showed lower MICs against gentamicin and each of three antimicrobials (ceftriaxone, ertapenem, and azithromycin) when used in combination.
Antimicrobial-resistant Neisseria gonorrhoeae is a major global public health concern. New treatment options are urgently needed to successfully treat multidrug-resistant (MDR) Neisseria gonorrhoeae infections. This study showed that gentamicin maintained excellent
susceptibility against clinical gonococcal isolates collected in 2016 and 2017, including MDR isolates. Combinations of gentamicin plus ertapenem, ceftriaxone, and azithromycin produced synergistic effects against certain MDR isolates. No antagonism was observed in any of the antimicrobial combinations, which may prove useful to guide clinical testing of combination therapies.
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