Gut microbiota has increasingly been shown to exert effects beyond the gastrointestinal tract, some of which are mediated through its metabolites, such as trimethylamine N-oxide (TMAO)—a compound converted by gut bacteria from dietary choline found predominantly in animal products that is associated with cardiovascular disease (CVD). However, a significant gap persists in human clinical trials assessing its potential causal role. This narrative review aims to present the current understanding of the gut microbiome, TMAO, and their relationship with CVD, while proposing future directions that may support the use of TMAO as a biomarker and guide potential interventions to reduce its harmful impact. Both animal and human studies have demonstrated a link between TMAO and CVD, with animal studies also indicating a causal effect—showing increased cardiovascular risk following TMAO administration and reduced risk when TMAO is eliminated. While direct extrapolation from animal models to humans is limited due to biological differences, these findings offer a foundation for the development of well-designed clinical trials in human populations. Although direct approaches to target TMAO—such as trimethylamine (TMA) lyase inhibitors and antisense oligonucleotide (ASO) therapy—have shown promising results in animal studies, they have yet to be investigated in human trials, leaving indirect strategies such as dietary changes and probiotics as the only currently available options.

Probiotics and postbiotics have gained increasing attention in microbiome research due to their potential roles in maintaining gut homeostasis and supporting human health. While probiotics are defined as live microorganisms that confer health benefits when administered in adequate amounts, postbiotics represent preparations of inanimate microorganisms and/or their components that also exert biological effects on the host. This narrative review provides an updated overview of the current knowledge on probiotics and postbiotics, with a particular focus on their mechanisms of action, production strategies, and emerging applications in human health. The review discusses key mechanisms through which probiotics and postbiotics interact with the host, including modulation of the gut microbiota, enhancement of epithelial barrier integrity, immune system regulation, metabolic modulation, and systemic signaling pathways. Advances in production technologies, ranging from conventional fermentation to innovative inactivation and stabilization approaches, are also examined, alongside challenges related to yield optimization, stability, safety, and standardization. Although a growing body of evidence suggests potential benefits of probiotics and postbiotics in metabolic, inflammatory, gastrointestinal, and immune-related conditions, much of the available data is derived from preclinical studies or small-scale clinical trials. Consequently, their clinical efficacy, optimal dosing, and long-term safety require further validation. By integrating current findings and highlighting existing gaps in the literature, this review aims to clarify the therapeutic potential of probiotics and postbiotics and to support the development of more robust, evidence-based strategies for their application in functional foods, supplements, and future biotherapeutic interventions.

The root of metabolic disease lies in the gastrointestinal tract, where nutrient absorption occurs. Within this environment, a diverse community of microorganisms exerts effects that extend beyond the intestinal barrier. Akkermansia muciniphila (A. muciniphila), one such bacterium, has been associated with enhanced intestinal integrity, reduced intestinal inflammation, weight loss, and improved insulin sensitivity, mediated through mucus fermentation, production of short-chain fatty acids (SCFAs), bacterial proteins, and extracellular vesicles (EVs). Research in this field is promising, yet far from perfect. Its clinical applicability remains limited by factors such as strain variability, scarcity of human intervention studies, and the lack of established causality. While associations have been consistently observed in both rodent and human studies, causality has thus far been demonstrated only in animal models. This issue is of critical importance, as metabolic disease remains highly prevalent, carries systemic consequences, and imposes a substantial burden on healthcare systems, underscoring the urgent need for alternative therapeutic strategies. The aim of this narrative review is to synthesize current knowledge on A. muciniphila and to highlight the key limitations consistently reported in the literature. By addressing these factors, the review seeks to provide realistic perspectives on its therapeutic potential and to outline directions for future research.

Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines the reasons behind the limited use of Lp(a) screening in clinical practice, assessing its role in cardiovascular risk, comparing it to traditional lipid markers and evaluating current assessment methods. It also explores existing and emerging treatments, including gene-silencing therapies, for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implied to be that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have a minimal impact on Lp(a), PCSK9-i lowers its levels by 20–25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the greatest reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether this reduction translates into CV benefits. These limitations should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether a reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL.

Prolonged hospitalization in cardiac patients is associated with increased morbidity and healthcare resource utilization, yet early biological factors linked to extended length of stay remain insufficiently defined. This study aimed to explore an integrative framework combining oral health parameters and targeted gut microbial markers to identify factors associated with prolonged hospitalization in cardiac patients. A comparative observational design was applied, including patients with short-term hospitalization (1–4 days) and prolonged hospitalization (≥25 days). Oral health status was evaluated using a standardized dental protocol at admission and longitudinally in patients with prolonged hospitalization. Targeted qRT-PCR-based quantification of selected gut bacterial markers was performed at admission and reassessed after one and two weeks. Temporal changes were calculated relative to baseline, and multivariate logistic regression models adjusted for age, sex, and major cardiac diagnoses were used to explore associations with prolonged hospitalization. Short-term hospitalized patients (n = 27) exhibited minimal oral health variation (+2%) and stable marker profiles. In contrast, patients with prolonged hospitalization (n = 30 for oral health; n = 18 for microbial markers) showed progressive changes over time. Oral health impairment increased by 3% after one week and 16% after two weeks, while targeted microbial marker variation showed modest directional changes. Integrative models combining oral health parameters and targeted microbial markers suggested potential complementary information alongside clinical variables, within the limits of an exploratory framework and limited sample size. These findings support the relevance of multidomain clinical and biological monitoring in the early identification of patients at risk for prolonged hospitalization.

Atherosclerotic cardiovascular disease (ASCVD) has been screened for decades using the traditional lipid profile, with by far the most emphasis on low-density lipoprotein-cholesterol (LDL). Even though more recent studies have suggested that there might be more to atherosclerosis than LDL, with inflammation and immune processes being some of the possible culprits, solid recommendations still haven’t been made regarding the potential use of other biomarkers. Most of the research has focused on Lipoprotein(a) [Lp(a)], an independent cardiovascular (CV) risk factor, with involvement in the progression of atherosclerosis, yet dramatically underused in clinical practice. This review aims to highlight the reasons for the lack of Lp(a) screening in clinical practice and to address these potential limitations. The study also reviews current screening and treatment methods and explores the hypothesis that proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) provide CV benefits due to a reduction in Lp(a), rather than LDL. A comprehensive review of the literature was conducted to assess the role of Lp(a) in cardiovascular disease risk, compare its predictive value to traditional lipid markers, and evaluate different measurement techniques, including mass spectrometry and immunoassays. Additionally, the review examined both current treatment strategies and emerging therapeutic approaches, such as gene-silencing therapies, that may offer new possibilities for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implying that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. However, Lp(a) has emerged as a potential biomarker for ASCVD, particularly in patients with high baseline levels or in patients who continue to develop CV events, despite having controlled LDL levels. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have minimal impact on Lp(a), PCSK9-i lower its levels by 20-25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the most reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether the reduction translates into CV benefits. Currently, there is more than one challenge that needs to be addressed when it comes to the use of Lp(a) as a reliable biomarker. Among them, the most mentioned in the literature are the lack of standardization and the absence of data to support a treatment. This should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether the reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL.