Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious burden", rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.

Recently, growing attention has focused on the impact of air pollution on gut microbiota as a possible mechanism by which air pollutant exposure increased the risk for chronic diseases, as evidenced by in vivo studies demonstrating important exposure-induced alterations in the diversity and relative abundance of gut bacterial taxa. This systematic review provides updated state-of-art findings of studies examining the impact of air pollution on the human gut microbiota. Databases PubMed, Scopus, and Web of Science were searched with the following strategy: “air poll*” AND “gut micro*” OR “intestinal micro*”; moreover, a total of 10 studies were included. Overall, there is the evidence that short-term and long-term exposure to air pollutants have the potential to alter the composition and diversity of gut microbiota; some studies also correlated air pollution exposure to adverse health effects (impaired fasting glucose, adverse pregnancy outcomes, and asthma attacks) via alterations in the composition and/or function of the gut microbiota. However, the evidence on this topic is still scarce, and large cohort studies are needed globally.

It is becoming increasingly clear that the human microbiota, also known as “the hidden organ”, possesses a pivotal role in numerous processes involved in maintaining the physiological functions of the host, such as nutrient extraction, biosynthesis of bioactive molecules, interplay with the immune, endocrine, and nervous systems, as well as resistance to the colonization of potential invading pathogens. In the last decade, the development of metagenomic approaches based on the sequencing of the bacterial 16s rRNA gene via Next Generation Sequencing, followed by whole genome sequencing via third generation sequencing technologies, has been one of the great advances in molecular biology, allowing a better profiling of the human microbiota composition and, hence, a deeper understanding of the importance of microbiota in the etiopathogenesis of different pathologies. In this scenario, it is of the utmost importance to comprehensively characterize the human microbiota in relation to disease pathogenesis, in order to develop novel potential treatment or preventive strategies by manipulating the microbiota. Therefore, this perspective will focus on the progress, challenges, and promises of the current and future technological approaches for microbiome profiling and analysis.

Several studies have attempted to relate the C. pneumoniae‐mediated inflammatory state with atherosclerotic cardiovascular diseases, providing inconsistent results. Therefore, we performed a meta‐analysis to clarify whether C. pneumoniae may contribute to the pathogenesis of atherosclerosis by enhancing inflammation. 12 case‐control, 6 cross‐sectional, and 7 prospective studies with a total of 10,176 patients have been included in this meta‐analysis. Odds Ratio (OR) with a 95% confidence interval was used to assess the seroprevalence of C. pneumoniae and differences between levels of inflammatory markers were assessed by standard mean differences. Publication bias was performed to ensure the statistical power. hsCRP, fibrinogen, interleukin‐ (IL‐) 6, TNF‐α, and IFN‐γ showed a significant increase in patients with atherosclerosis compared to healthy controls (P < 0.05), along with a higher seroprevalence of C. pneumoniae (OR of 3.11, 95% CI: 2.88–3.36, P < 0.001). More interestingly, hsCRP, IL‐6, and fibrinogen levels were significantly higher in C. pneumoniae IgA seropositive compared to seronegative atherosclerotic patients (P < 0.0001). In conclusion, the present meta‐analysis suggests that C. pneumoniae infection may contribute to atherosclerotic cardiovascular diseases by enhancing the inflammatory state, and, in particular, seropositivity to C. pneumoniae IgA, together with hsCRP, fibrinogen, and IL‐6, may be predictive of atherosclerotic cardiovascular risk.

Research in Chlamydia trachomatis and Chlamydia pneumoniae has gained new traction due to recent advances in molecular biology, namely the widespread use of the metagenomic analysis and the development of a stable genomic transformation system, resulting in a better understanding of Chlamydia pathogenesis. C. trachomatis, the leading cause of bacterial sexually transmitted diseases, is responsible of cervicitis and urethritis, and C. pneumoniae, a widespread respiratory pathogen, has long been associated with several chronic inflammatory diseases with great impact on public health. The present review summarizes the current evidence regarding the complex interplay between C. trachomatis and host defense factors in the genital micro-environment as well as the key findings in chronic inflammatory diseases associated to C. pneumoniae.

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research.