The Role of the Microbiota in the Diabetic Peripheral Artery Disease.

Vascular complications of diabetes mellitus represent a major public health problem. Although many steps forward have been made to define the causes and to find the best possible therapies, the problem remains crucial. In recent years, more and more evidences have defined a link between microbiota and the initiation, promotion, and evolution of atherosclerotic disease, even in the diabetic scenario. There is an urgency to develop the knowledge of modern medicine about the link between gut microbiota and its host's metabolic pathways, and it would be useful to understand and justify the interindividual diversity of clinical disease presentation of diabetic vascular complication even if an optimization of pharmacological treatment has been made or in the case of young patients where hypertension, dyslipidemia, and diabetes are not able to justify a very quick progress of atherosclerotic process. The aim of the present review is to gather all the best available evidence in this regard and to define a new role of the microbiota in this field, from biomarker to possible therapeutic target.

Infección arterial causada por Listeria monocytogenes: a propósito de dos casos. Eficacia del abordaje combinado precoz y tratamiento supresivo oral / Arterial infection caused by Listeria monocytogenes: Report of two cases. The efficacy of an early combined approach and oral suppressive treatment

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Coxiella burnetii endocarditis on bioprosthetic aortic valve, with peripheral arterial embolism.

Acute limb ischemia related to Coxiella burnetii endocarditis is rare. We report an original case of a 68-year-old man hospitalized for recurrent acute left limb ischemia in a context of atrial flutter, which revealed C. burnetii endocarditis. This case illustrates that even if embolic events are uncommon, septic embolisms must be systematically searched for in case of C. burnetii endocarditis. Conversely, extensive etiologic explorations must be performed in case of systemic embolism. New molecular techniques represent a major step forward in infective endocarditis diagnosis. Finally, diagnosis must be suspected in case of unexplained fever, inflammatory syndrome, or embolic event, especially in patients at risk. Conversely, in case of chronic Q fever, an immunodeficiency cause must be researched.

Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes.

OBJECTIVE: Multiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis. METHODS: Plasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia. The controls (n = 22) were age- and sex-matched participants who had no peripheral arterial disease or history of stroke or myocardial infarction. Patients with chronic kidney disease were excluded. Metabolites and internal standards were measured using high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Plasma metabolite concentrations differed significantly between the advanced atherosclerosis and control cohorts. After adjustment for traditional atherosclerosis risk factors, indole (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75-0.95; P = .004), tryptophan (OR, <0.001; 95% CI, <0.001-0.003; P < .001), indole-3-propionic acid (OR, 0.27; 95% CI, 0.019-0.91; P = .02), and indole-3-aldehyde (OR, 0.12; 95% CI, 0.014-0.92; P = .04) concentrations negatively associated with advanced atherosclerosis, whereas the kynurenine/tryptophan ratio (OR, 61.7; 95% CI, 1.9->999; P = .02) was positively associated. Furthermore, tryptophan and indole-3-propionic acid concentrations (Spearman coefficients of 0.63 and 0.56, respectively; P < .001) correlated with the ankle-brachial index, a surrogate for overall atherosclerotic disease burden. Fourteen patients experienced a major postoperative cardiac complication within 30 days in the advanced atherosclerosis cohort, which was associated with baseline kynurenine/tryptophan ratio (P = .001) and hippuric acid (P = .03). In a multivariate analysis, only the kynurenine/tryptophan ratio remained significantly associated with a postoperative cardiac complication (OR, 44.1; 95% CI, 3.3-587.1; P = .004). Twenty patients in the advanced atherosclerosis cohort experienced a major adverse cardiac event during the follow-up period, which was associated with hippuric acid (P = .002) and the kynurenine/tryptophan ratio (P < .001) at baseline. Both hippuric acid and the kynurenine/tryptophan ratio were independently associated with a major adverse cardiac event in multivariate analyses that included diabetes mellitus. CONCLUSIONS: Specific microbe-derived metabolite signatures associate with advanced human atherosclerosis and postoperative cardiac complications. We suggest that these metabolites are potential novel biomarkers for atherosclerotic disease burden and that further investigation into mechanistic links between defined microbial metabolic pathways and cardiovascular disease is warranted.

Quantification of periodontal pathogens in vascular, blood, and subgingival samples from patients with peripheral arterial disease or abdominal aortic aneurysms.

BACKGROUND: The aim of this investigation is to quantify periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, and Tannerella forsythia) in vascular, blood, and subgingival samples. As a secondary objective, two molecular bacterial identification methods (nested polymerase chain reaction [PCR] and quantitative PCR [qPCR]) are compared. METHODS: Seventy consecutive patients provided a vascular lesion, a blood sample, and 36 subgingival samples. Bacterial DNA was extracted, and qPCR was used to determine the prevalence and amounts of the target pathogens in each sample. Nested PCR was performed only in the samples from vascular lesions. Periodontal examination was performed in 42 patients. Mann-Whitney U or χ(2) tests were used to compare microbiologic results according to periodontal diagnosis. RESULTS: All targeted periodontal pathogens (A. actinomycetemcomitans, P. gingivalis, T. forsythia, or C. rectus) were detected in subgingival samples, with a prevalence rate of 72.2%, 47.2%, 74.3%, and 82.9%, respectively. In 7.1% and 11.4% of vascular and blood samples, bacterial DNA was detected. One patient was positive for A. actinomycetemcomitans in the three types of samples. No differences were found in the levels of targeted bacteria when comparing patients with and without periodontitis. Prevalence rates obtained with nested PCR were significantly higher than those obtained with qPCR. CONCLUSIONS: The presence of A. actinomycetemcomitans was demonstrated in vascular, blood, and subgingival samples in one of 36 patients. These results, although with a very low frequency, may support the hypothesis of a translocation of periodontal pathogens from subgingival microbiota to the bloodstream and then to atheromatous plaques in carotid or other peripheral arteries. Nested PCR is not an adequate method for identifying DNA of periodontal pathogens in low quantities because of the high number of false-negative results.

Differential identification of atypical pneumonia pathogens in aorta and internal mammary artery related to ankle brachial index and walking distance.

BACKGROUND: We studied the existence of agents in aorta biopsies, such as Chlamydia pneumoniae, cytomegalovirus, and Mycoplasma pneumoniae, that are thought to have a role in atherosclerosis etiopathogenesis role, and their association with peripheral artery disease. MATERIALS AND METHODS: We examined aorta wall and internal mammarian artery (IMA) biopsies taken from two different places in 63 patients in whom coronary artery bypass was performed. In these biopsies, we evaluated the deoxyribonuclease (DNA) of these microorganisms using polymerase chain reaction. From the same patients, we recorded the ankle brachial index, road walking distance information, lipid profile, C-reactive proteins, blood parameters such as fibrinogen, and the patient's operation data. RESULTS: In the nine aorta biopsies taken from 63 patients, we isolated C pneumoniae DNA. In IMA biopsies taken from the same patients, we detected no microorganism DNA (P < 0.001). In the same aorta biopsies, we found no cytomegalovirus or M pneumoniae DNA. We examined 12 patients using an index value of 0.9 in the ankle brachial index evaluation; eight had C pneumoniae in the aorta biopsies (P < 0.001). CONCLUSIONS: We found a significant relationship between C pneumoniae DNA and the existence of peripheral artery disease. In the development of atherosclerosis with C pneumoniae, there may be a determinant pathogen in both the aorta and the peripheral arteries. The nonexistence of C pneumoniae DNA in the IMA biopsies may indicate infectious agents because of the predominant endothelial functions in this artery, and thus its resistance to atherosclerosis.

Whole-blood platelet aggregation by Porphyromonas gingivalis in patients with peripheral arterial disease.

OBJECTIVES: To measure platelet aggregation promoted by Porphyromonas gingivalis (P. gingivalis) in whole blood, and to investigate the relation between P. gingivalis and peripheral arterial disease (PAD). METHODS AND RESULTS: Subjects were 30 patients who were diagnosed as having PAD (PAD Group), and 26 healthy adults without subjective symptoms or arteriosclerosis as a control (Control Group). PAD patients were classified depending on severity levels by Fontaine classification or toe pressure (TP). Twelve-minute changes of electrical impedance after adding P. gingivalis to whole blood was 10.2 ± 4.8 (range, 5.1-14.3) ohm in PAD Group, and 6.1 ± 5.6 (range, 0.2-10.8) ohm in Control Group. PAD Group showed significantly stronger whole-blood platelet aggregation by P. gingivalis. The patients with more severe PAD showed stronger whole-blood platelet aggregation by P. gingivalis. PAD Group had significantly higher serum IgG against P. gingivalis titers than Control Group. In PAD patients with teeth, there was a strong positive correlation between whole-blood platelet aggregation and IgG against P. gingivalis titers. CONCLUSIONS: Platelet aggregation promoted by P. gingivalis was significantly high in PAD patients, and was related to the deterioration of their symptoms even in whole blood, which was the environment closer to physiological conditions.

High frequency of Chlamydophila pneumoniae infections: patients with peripheral arterial disease and those with risk factors for cardiovascular diseases compared to normal subjects.

The role of bacterial infections, mainly Chlamydophila pneumoniae, on atherosclerotic processes as well as the therapeutic utility of additional antibiotic treatment is still an open question. In this study we compared the serological profiles of 160 patients (80 with peripheral arterial disease (PAD), diagnosed with an ankle/brachial index (ABI) ≤ 0.9 and 80 with risk factors for cardiovascular disease - CVD) with those of 80 healthy subjects, serum levels of specific C. pneumoniae antibodies using the microimmunofluorescence test. Our results show that PAD patients had a higher frequency of C. pneumoniae infection than those with risk factors for cardiovascular disease. This frequency was lower if compared to the previous two groups in controls. 44 out of the 80 (55%) patients with PAD and 34 out of the 80 (42.58%) subjects with risk factors for cardiovascular disease were seropositive while only 24 of the 80 (30%) healthy subjects showed seropositivity to C. pneumoniae. Furthermore, higher anticorpal titers were also found in patients with peripheral arterial disease and in patients with cardiovascular risk factors if compared to healthy subjects. On the basis of these results, we confirm that C. pneumoniae infection is frequent in peripheral arterial disease patients and we believe that it could be considered as an additional risk factor involved in the pathogenesis of this disease.