Background: Arterial hypertension and its organ sequelae show characteristics of T cell–mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage. Methods: To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout–deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg ^–1 ·d ^–1 subcutaneous) for 14 days. To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg ^–1 ·d ^–1 subcutaneous) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate. Results: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II–infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout–deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell–depleted angiotensin II–infused mice, suggesting the effect is regulatory T cell–dependent. Conclusions: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease.

Cardiovascular diseases (CVDs) are a leading cause of global morbidity and mortality, significantly driven by chronic inflammation. Interleukin-6 (IL-6) and interleukin-1β (IL-1β) are critical inflammatory cytokines implicated in CVD progression. This systematic review evaluates the roles of IL-6 and IL-1β in CVDs by synthesizing data from relevant studies to understand their impact on cardiovascular outcomes and identify potential therapeutic interventions. A comprehensive literature search was conducted using PubMed and Embase, covering studies from January 2014 to December 2024. Inclusion criteria encompassed studies investigating IL-6 and/or IL-1β in CVDs, including human and relevant animal models, and reporting clinical outcomes, molecular mechanisms, or therapeutic interventions. Data extraction and quality assessment were performed independently by two reviewers. Our review included 12 studies focusing on the roles of IL-6 and IL-1β in various CVDs. Elevated IL-6 levels were significantly associated with peripheral artery disease, myocardial infarction, and heart failure, while IL-1β levels were linked to worse outcomes in coronary artery disease and heart failure. Meta-analyses indicated a significant association between higher IL-6 and IL-1β levels and increased risk of adverse cardiovascular events. These findings suggest that targeting IL-6 and IL-1β could offer promising therapeutic strategies for reducing inflammation and improving cardiovascular outcomes.

This study provides a comprehensive assessment of how urban-rural divides influence gut microbial diversity and composition across the distinct geographical landscapes of Kazakhstan, elucidating the intricate interplay between lifestyle, environment, and gut microbiome. In this prospective cohort study, we enrolled 651 participants from urban centers and rural settlements across Kazakhstan, following ethical approval and informed consent. Comprehensive demographic, dietary, and stool sample data were collected. 16S rRNA gene sequencing and shotgun metagenomics techniques were employed to delineate the intricate patterns of the gut microbiome. A rigorous statistical framework dissected the interplay between urbanization gradients, geography, dietary lifestyles, and microbial dynamics. Our findings demonstrate a stark microbial divide between urban and rural gut ecosystems. The study found significant differences in gut microbiome diversity and composition between urban and rural populations in Kazakhstan. Urban microbiomes exhibited reduced diversity, higher Firmicutes/Bacteroidetes ratios, and increased prevalence of genera Coprococcus and Parasutterella . In contrast, rural populations had greater microbial diversity and abundance of Ligilactobacillus , Sutterella , and Paraprevotella . Urbanization also influenced dietary patterns, with urban areas consuming more salt, cholesterol, and protein, while rural areas had diets richer in carbohydrates and fiber. The study also identified distinct patterns in the prevalence of antibiotic resistance genes and virulence factors between urban and rural gut microbiomes. This study sheds light on how urbanization may be deeply involved in shaping the intricate mosaic of the gut microbiome across Kazakhstan’s diverse geographical and dietary landscapes, underscoring the complex interplay between environmental exposures, dietary lifestyles, and the microbial residents inhabiting our intestines. IMPORTANCE: The study examined gut microbiome composition across diverse geographical locations in Kazakhstan, spanning urban centers and rural settlements. This allows for thoroughly investigating how urbanization gradients and geographic factors shape the gut microbiome. The study's examination of the gut resistome and prevalence of virulence-associated genes provide essential insights into the public health implications of urbanization-driven microbiome alterations. Collecting comprehensive demographic, dietary, and stool sample data enables the researchers to better understand the relationships between urbanization, nutritional patterns, and gut microbiome composition. The findings have important implications for understanding how urbanization-driven microbiome changes may impact human health and well-being, paving the way for tailored interventions to restore a balanced gut microbial ecology.

Objective: Changes in the gut microbiota are increasingly recognised to be involved in many diseases. This ecosystem is known to be shaped by many factors, including climate, geography, host nutrition, lifestyle and medication. Thus, knowledge of varying populations with different habits is important for a better understanding of the microbiome. Design: We therefore conducted a metagenomic analysis of intestinal microbiota from Kazakh donors, recruiting 84 subjects, including male and female healthy subjects and metabolic syndrome (MetS) patients aged 25–75 years, from the Kazakh administrative centre, Astana. We characterise and describe these microbiomes, the first deep-sequencing cohort from Central Asia, in comparison with a global dataset (832 individuals from five countries on three continents), and explore correlations between microbiota, clinical and laboratory parameters as well as with nutritional data from Food Frequency Questionnaires. Results: We observe that Kazakh microbiomes are relatively different from both European and East Asian counterparts, though similar to other Central Asian microbiomes, with the most striking difference being significantly more samples falling within the Prevotella -rich enterotype, potentially reflecting regional diet and lifestyle. We show that this enterotype designation remains stable within an individual over time in 82% of cases. We further observe gut microbiome features that distinguish MetS patients from controls (eg, significantly reduced Firmicutes to Bacteroidetes ratio, Bifidobacteria and Subdoligranulum , alongside increased Prevotella ), though these overlap little with previously published reports and thus may reflect idiosyncrasies of the present cohort. Conclusion: Taken together, this exploratory study describes gut microbiome data from an understudied population, providing a starting point for further comparative work on biogeography and research on widespread diseases. Trial registration number: ISRCTN37346212 ; Post-results.

Short-chain fatty acids (SCFAs), produced through fermentation of dietary fibers by gut bacteria, play a central role in modulating cardiovascular function and heart failure (HF) development. The progression of HF is influenced by intestinal barrier dysfunction and microbial translocation, where SCFAs serve as key mediators in the gut–heart axis. This review examines the complex metabolic interactions between SCFAs and other gut microbiota metabolites in HF, including their relationships with trimethylamine N-oxide (TMAO), aromatic amino acids (AAAs), B vitamins, and bile acids (BAs). We analyze the associations between SCFA production and clinical parameters of HF, such as left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and glomerular filtration rate (GFR). Gaining insights into metabolic networks offers new potential therapeutic targets and prognostic markers for managing heart failure, although their clinical significance needs further exploration.

Background: Reduced short-chain fatty acids (SCFAs) in inflammatory bowel disease (IBD) impair the gut barrier and immune function, promoting inflammation and highlighting microbiome-targeted therapies’ therapeutic potential. The purpose of this meta-analysis was to study the changes in SCFAs in IBD and their potential role in the occurrence and development of IBD. Methods: The analysis employed a random-effects model to assess the standardized mean difference (SMD) with a 95% confidence interval. A literature search was conducted in databases from 2014 to 20 July 2024 to identify studies investigating SCFAs in IBD. Results: Subgroup analyses revealed a significant reduction in fecal SCFA levels—specifically butyrate, acetate, and propionate—in all IBD subgroups compared to healthy controls. Active IBD showed a greater decrease in butyrate (p = 0.004), and UC showed a notable reduction in propionate (p = 0.03). When comparing UC and CD, differences were observed mainly in propionate (SMD = −0.76, p = 0.00001). Dietary interventions in IBD patients led to increased SCFA levels, with butyrate showing the most improvement (SMD = 1.03), suggesting the potential therapeutic value of dietary modulation. Conclusions: In conclusion, this meta-analysis demonstrates a significant reduction in fecal SCFA levels in patients with IBD, particularly during active phases of the disease and most markedly in CD.