The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.

The world is experiencing a sudden surge in urban population, especially in developing Asian and African countries. Consequently, the global burden of cardio-metabolic disease (CMD) is also rising owing to gut microbiome dysbiosis due to urbanization factors such as mode of birth, breastfeeding, diet, environmental pollutants, and soil exposure. Dysbiotic gut microbiome indicated by altered Firmicutes to Bacteroides ratio and loss of beneficial short-chain fatty acids-producing bacteria such as Prevotella, and Ruminococcus may disrupt host-intestinal homeostasis by altering host immune response, gut barrier integrity, and microbial metabolism through altered T-regulatory cells/T-helper cells balance, activation of pattern recognition receptors and toll-like receptors, decreased mucus production, elevated level of trimethylamine-oxide and primary bile acids. This leads to a pro-inflammatory gut characterized by increased pro-inflammatory cytokines such as tumour necrosis factor-α, interleukin-2, Interferon-ϒ and elevated levels of metabolites or metabolic endotoxemia due to leaky gut formation. These pathophysiological characteristics are associated with an increased risk of cardio-metabolic disease. This review aims to comprehensively elucidate the effect of urbanization on gut microbiome-driven cardio-metabolic disease. Additionally, it discusses targeting the gut microbiome and its associated pathways via strategies such as diet and lifestyle modulation, probiotics, prebiotics intake, etc., for the prevention and treatment of disease which can potentially be integrated into clinical and professional healthcare settings.

The intricate relationship between hydrogen sulfide (H2S), gut microbiota, and sirtuins (SIRTs) can be seen as a paradigm axis in maintaining cellular homeostasis, modulating oxidative stress, and promoting mitochondrial health, which together play a pivotal role in aging and neurodegenerative diseases. H2S, a gasotransmitter synthesized endogenously and by specific gut microbiota, acts as a potent modulator of mitochondrial function and oxidative stress, protecting against cellular damage. Through sulfate-reducing bacteria, gut microbiota influences systemic H2S levels, creating a link between gut health and metabolic processes. Dysbiosis, or an imbalance in microbial populations, can alter H2S production, impair mitochondrial function, increase oxidative stress, and heighten inflammation, all contributing factors in neurodegenerative diseases such as Alzheimer's and Parkinson's. Sirtuins, particularly SIRT1 and SIRT3, are NAD+-dependent deacetylases that regulate mitochondrial biogenesis, antioxidant defense, and inflammation. H2S enhances sirtuin activity through post-translational modifications, such as sulfhydration, which activate sirtuin pathways essential for mitigating oxidative damage, reducing inflammation, and promoting cellular longevity. SIRT1, for example, deacetylates NF-κB, reducing pro-inflammatory cytokine expression, while SIRT3 modulates key mitochondrial enzymes to improve energy metabolism and detoxify reactive oxygen species (ROS). This synergy between H2S and sirtuins is profoundly influenced by the gut microbiota, which modulates systemic H2S levels and, in turn, impacts sirtuin activation. The gut microbiota-H2S-sirtuin axis is also essential in regulating neuroinflammation, which plays a central role in the pathogenesis of neurodegenerative diseases. Pharmacological interventions, including H2S donors and sirtuin-activating compounds (STACs), promise to improve these pathways synergistically, providing a novel therapeutic approach for neurodegenerative conditions. This suggests that maintaining gut microbiota diversity and promoting optimal H2S levels can have far-reaching effects on brain health.

The gut microbiota is important in the development and progression of metabolic illnesses such type 2 diabetes, cardiovascular disease (CVD), and obesity. This diverse community of microorganisms controls a variety of physiological functions, including metabolism, inflammation, and immune response. Understanding these interactions has resulted in novel therapeutic options, including microbiome supplementation. The gut microbiome is extremely susceptible to dietary changes, which can alter its makeup and function, influencing metabolite synthesis that affects host health. Certain metabolites, such as butyrate and propionate, have been proven to protect against metabolic illnesses, whereas trimethylamine has been linked to CVD. Prebiotics, probiotics, synbiotics, and postbiotics are being investigated by researchers as ways to change the gut microbiome and boost metabolic health. Despite advances in therapy and lifestyle adjustments, the prevalence of metabolic syndrome is increasing, emphasizing the need for new medicines.

Our understanding of gut microbial populations and their immense influence on host immunity, health, and diseases has increased deeply in recent years. Numerous reports have identified the role of mosquito and mammalian gut microbiota in the modulation of host susceptibility to Plasmodium infection. Artemisinin resistance in malaria-endemic regions necessitates the development of new, safer, and more affordable treatments to supplement existing therapies. In this review, we compiled a colossal amount of data from numerous studies that have assessed the roles played by gut microbial communities in Plasmodium infection, progression, transmission, and severity. Most interestingly, our study points to the overwhelming evidence from experimental studies in mural malaria to human trials, suggesting that the presence of lactic acid bacteria in the gut microbiota of mammalian hosts provides a great degree of protection against malaria. Therefore, our study provides a compelling narrative for probiotic administration as an adjunct therapy for combatting malaria.

Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. Despite advances in treatment modalities, its prevalence continues to rise, notably among younger populations. Unhealthy dietary habits, sedentary routines, and obesity have been identified as one of the key contributors to the development of colorectal cancer, apart from genetic and epigenetic modifications. Recognizing the profound impact of diet and lifestyle on the intricate gut microbiota ecosystem offers a promising avenue for understanding CRC development and its treatment. Gut dysbiosis, characterized by imbalances favoring harmful microbes over beneficial ones, has emerged as a defining feature of CRC. Changes in diet and lifestyle can profoundly alter the composition of gut microbes and the metabolites they produce, potentially contributing to CRC onset. Focusing on recent evidence, this review discussed various dietary factors, such as high consumption of red and processed meats and low fiber intake, and lifestyle factors, including obesity, lack of physical activity, smoking, and excessive alcohol consumption, that influence the gut microbiome composition and elevate CRC risk.

This review delves into the complex interplay between obesity-induced gut microbiota dysbiosis and the progression of type 2 diabetes mellitus (T2DM), highlighting the potential of natural products in mitigating these effects. By integrating recent epidemiological data, we aim to provide a nuanced understanding of how obesity exacerbates T2DM through gut flora alterations.

Advances in research have underscored the significance of bioactive ingredients in natural foods, capable of restoring gut microbiota balance, thus offering a promising approach to manage diabetes in the context of obesity. These findings build upon the traditional use of medicinal plants in diabetes treatment, suggesting a deeper exploration of their mechanisms of action. This comprehensive manuscript underscores the critical role of targeting gut microbiota dysbiosis in obesity-related T2DM management and by bridging traditional knowledge with current scientific evidence; we highlighted the need for continued research into natural products as a complementary strategy for comprehensive diabetes care.

Breast cancer survivors with obesity are at a high risk of cancer recurrence, comorbidity, and mortality. This review aims to systematically evaluate the effects of combined aerobic and resistance training (CART) on body composition, lipid homeostasis, inflammation, adipokines, cancer-related fatigue, sleep, and quality of life in breast cancer patients and survivors with overweight/obesity. An electronic search was conducted in PubMed, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases from inception up to January 8, 2024. Randomized controlled trials (RCTs) meeting the inclusion criteria were selected for the analysis. The Cochrane risk of bias tool was used to assess eligible studies, and the GRADE method to evaluate the quality of evidence. A random-effects model was used, and data were analyzed using mean (MD) and standardized mean differences (SMD) for continuous variables with 95% confidence intervals (CI). We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. A total of 17 randomized controlled trials were included in the systematic review involving 1,148 female patients and survivors (mean age: 54.0 ± 3.4 years). The primary outcomes showed significant improvements in body mass index (SMD -0.57 kg/m2, p = 0.04), body fat (SMD -0.50%, p = 0.02), fat mass (SMD -0.63 kg, p = 0.04), hip circumference (MD -3.14 cm, p = 0.02), and fat-free mass (SMD 1.03 kg, p < 0.001). The secondary outcomes indicated significant increases in high-density lipoprotein cholesterol (MD -0.05 mmol/L, p = 0.008), natural killer cells (SMD 0.42%, p = 0.04), reductions in triglycerides (MD -81.90 mg/dL, p < 0.01), total cholesterol (SMD -0.95 mmol/L, p < 0.01), tumor necrosis factor α (SMD -0.89 pg/mL, p = 0.03), and leptin (SMD -0.63 ng/mL, p = 0.03). Also, beneficial alterations were found in cancer-related fatigue (SMD -0.98, p = 0.03), sleep (SMD -1.17, p < 0.001), and quality of life (SMD 2.94, p = 0.02) scores. There was very low to low confidence in the estimated effect of most of the outcomes. The present findings reveal that CART could be considered an adjunct therapy in supporting the conventional clinical approach observed following exercise. However, further high-quality research is needed to evaluate whether CART would be a valuable intervention to lower aggressive pharmacologic use in breast cancer patients with overweight/obesity.

The human microbiome, particularly the gut microbiome, has emerged as a central determinant of health and disease. Dysbiosis, an imbalance in the microbial composition of the gut, is associated with a variety of metabolic and other diseases, highlighting the potential for microbiota-targeted treatments. Fecal microbiota transplantation has received considerable attention as a promising therapy to modulate the gut microbiome and restore microbial homeostasis. However, challenges remain, including standardization, safety, and long-term efficacy. This review summarizes current knowledge on fecal microbiota transplantation and describes the next generation therapies targeting microbiome. This review looked at the mechanistic understanding of fecal microbiota transplantation and alternative strategies, elucidating their potential role in improving dysbiosis-associated metabolic disorders, such as obesity, and type 2 diabetes and others. Additionally, this review discussed the growing application of therapies targeting the gut microbiome. Insights from clinical trials, preclinical studies, and emerging technologies provide a comprehensive overview of the evolving landscape of microbiome-based interventions. Through a critical assessment of current advances and prospects, this review aims to highlight the therapeutic potential of targeting gut microbiome and pave the way for innovative approaches in precision medicine and personalized treatments.

Microbiota modulation, the intentional change in the structure and function of the microbial community, is an emerging trajectory that holds the promise to mitigate an infinite number of health issues. The present review illustrates the underlying principles of microbiota modulation and the various applications of this fundamental process to human health, healthcare management, and pharmacologic interventions. Different strategies, directing on dietary interventions, fecal microbiota transplantation, treatment with antibiotics, bacteriophages, microbiome engineering, and modulation of the immune system, are described in detail. This therapeutic implication is reflected in clinical applications to gastrointestinal disorders and immune-mediated diseases for microbiota-modulating agents. In addition to this, the review outlines the challenges of translating researched outcomes into clinical practice to consider safety and provides insights into future research directions of this rapidly developing area.

Cardiovascular diseases, including myocardial infarction, remain a leading cause of death globally. Emerging evidence suggests the gut microbiota plays a crucial role in cardiovascular health. This study aims to explore the impact of gut microbiota on myocardial infarction using a mouse model.

The research utilizes a multi-omics approach, including 16S rDNA sequencing and LC-MS-based metabolomics to analyze fecal and serum samples from mice modeled to mimic myocardial infarction. This methodology allows for a comprehensive analysis of microbial populations and their metabolic output.

The findings reveal a significant reduction in gut microbiota α-diversity in mice with induced myocardial infarction compared to healthy controls. Notably, there is an increase in populations of Fusobacteria and Clostridia. Metabolomic analysis indicates disruptions in amino acid and energy metabolism, suggesting a metabolic dysregulation linked to myocardial health.

The study proposes a novel microbiota-metabolite-myocardium axis, where specific microbial metabolites may directly affect heart health. This connection points to the gut microbiota as a potential player in the pathogenesis of myocardial infarction and may open new therapeutic avenues targeting the gut microbiome to combat cardiovascular diseases.

Microbial metabolites have been indicated to communicate with the host's endocrine system, regulating hormone production, immune-endocrine communications, and interactions along the gut-brain axis, eventually affecting the occurrence of endocrine cancer. Furthermore, microbiota metabolites such as short-chain fatty acids (SCFAs) have been found to affect the tumor microenvironment and boost immunity against tumors. SCFAs, including butyrate and acetate, have been demonstrated to exert anti-proliferative and anti-protective activity on pancreatic cancer cells. The employing of microbial metabolic products in conjunction with radiation and chemotherapy has shown promising outcomes in terms of reducing treatment side effects and boosting effectiveness. Certain metabolites, such as valerate and butyrate, have been made known to improve the efficiency of CAR T-cell treatment, whilst others, such as indole-derived tryptophan metabolites, have been shown to inhibit tumor immunity. This review explores the intricate interplay between microbial metabolites and endocrine tumorigenesis, spanning mechanistic insights to the discovery of potential therapeutic biomarkers.

In 2016, the International Scientific Association for Probiotics and Prebiotics (ISAPP) provided a new definition of a prebiotic as "a substrate that is selectively utilized by host microorganisms conferring a health benefit" [...].

Sickle cell disease (SCD), a distinctive and often overlooked illness in the 21st century, is a congenital blood disorder characterized by considerable phenotypic diversity. It comprises a group of disorders, with sickle cell anemia (SCA) being the most prevalent and serious genotype. Although there have been some systematic reviews of global data, worldwide statistics regarding SCD prevalence, morbidity, and mortality remain scarce. In developed countries with a lower number of sickle cell patients, cutting-edge technologies have led to the development of new treatments. However, in developing settings where sickle cell disease (SCD) is more prevalent, medical management, rather than a cure, still relies on the use of hydroxyurea, blood transfusions, and analgesics. This is a disease that affects red blood cells, consequently affecting most organs in diverse manners. We discuss its etiology and the advent of new technologies, but the aim of this study is to understand the various types of nutrition-related studies involving individuals suffering from SCD, particularly in Africa. The interplay of the environment, food, gut microbiota, along with their respective genomes collectively known as the gut microbiome, and host metabolism is responsible for mediating host metabolic phenotypes and modulating gut microbiota. In addition, it serves the purpose of providing essential nutrients. Moreover, it engages in direct interactions with host homeostasis and the immune system, as well as indirect interactions via metabolites. Nutrition interventions and nutritional care are mechanisms for addressing increased nutrient expenditures and are important aspects of supportive management for patients with SCD. Underprivileged areas in Sub-Saharan Africa should be accompanied by efforts to define and promote of the nutritional aspects of SCD. Their importance is key to maintaining well-being and quality of life, especially because new technologies and products remain limited, while the use of native medicinal plant resources is acknowledged.

The escalating misuse of antibiotics, particularly broad-spectrum antibiotics, has emerged as a pivotal driver of drug resistance. Among these agents, tetracyclines are widely prescribed for bacterial infections, but their indiscriminate use can profoundly alter the gut microbiome, potentially compromising both their effectiveness and safety. This review delves into the intricate and dynamic interplay between tetracyclines and the gut microbiome, shedding light on their reciprocal influence. By exploring the effects of tetracyclines on the gut microbiome and the impact of gut microbiota on tetracycline therapy, we seek to gain deeper insights into this complex relationship, ultimately guiding strategies for preserving antibiotic efficacy and mitigating resistance development.

This Special Issue, titled "Probiotics and Prebiotics in Cardiovascular Diseases", encompasses two comprehensive review articles examining the potential of gut-microbiota-targeted reprogramming interventions designed to prevent the onset and progression of cardiovascular diseases [...].

Sepsis is a complex clinical disorder with heterogeneous etiological factors. Given its high mortality rate, it is considered a global health issue. Recently, the link between gut microbiota and their metabolites, especially short-chain fatty acids, in the pathophysiology of sepsis has been reported. However, there are few findings to confirm this relationship. This study aimed to evaluate some key gut microbiota members, pathogenic bacteria, and short-chain fatty acids in non-ICU patients with sepsis caused by bacteremia compared to a control group. In this case-control study, 45 stool samples from patients with sepsis and 15 healthy persons were collected from October 2021 to August 2022 in Tabriz, Iran. The position of some gut microbiota members and the main short-chain fatty acids concentration were assessed in the two groups by the Q-PCR and the high-performance liquid chromatography system. Faecalibacterium prausnitzii and Bifidobacterium sp. As bacterial with protective features in non-ICU patients with sepsis decreased significantly. Moreover, the concentrations of acetic acid and propionic acid significantly decreased in this group compared to the healthy volunteers. In contrast, the pathogenic bacteria members such as Enterobacteriaceae and Bacteroides sp. Increased significantly in the patients compared to the healthy individuals. The concentration of butyric acid decreased in the patients, but this change was not significant in the two groups. Protective and immune functions of F. prausnitzii and Bifidobacterium sp., as well as acetate and propionate, are evident. In this investigation, this profile was significantly reduced in non-ICU patients with sepsis compared to the control group.

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject's phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.

The PI3K/AKT/mTOR signaling pathway may play crucial roles in the pathogenesis of obesity and diabetes mellitus, as well as metabolic syndromes, which could also be risk factors for cardio-metabolic disorders. Consistently, it has been shown that beneficial effects may be convoyed by the modulation of the PI3K/AKT/mTOR pathway against the development of these diseases. Importantly, the PI3K/AKT/mTOR signaling pathway can be modulated by probiotics. Probiotics have a variety of beneficial properties, with the potential of treating specific diseases such as immune-related diseases, which are valuable to human health. In addition, an increasing body of work in the literature emphasized the contribution of genetically modified probiotics. There now seems to be a turning point in the research of probiotics. A better understanding of the interactions between microbiota, lifestyle, and host factors such as genetics and/or epigenetics might lead to a novel therapeutic approach with probiotics for these diseases. This study might provide a theoretical reference for the development of genetically modified probiotics in health products and/or in functional foods for the treatment of cardio-metabolic disorders.