Unique intestinal microflora and metabolic profile in different stages of hypertension reveal potential biomarkers for early diagnosis and prognosis.

Introduction. Hypertension is the most prevalent chronic disease and a major risk factor for cardiovascular and cerebrovascular diseases.Gap statement. However, there has been no substantial breakthrough in aetiology, new drug targets, and drug development of hypertension in recent 50 years.Research aim. Therefore, this study was to screen unique intestinal microbiome and serum metabolic biomarkers which can early diagnose and track the prognosis of hypertension patients in different periods, and analyse its underlying mechanisms and functions.Methods. Four groups of stool and serum samples, including healthy controls (HCs), prehypertension (PHT), hypertension (HT), and hypertension-related complications (HTC), were collected. Microbial diversity assessed using 16S rRNA sequencing. The metabolites in serum samples were detected through LC-MS/MS analysis.Results. The composition of gut microbiota in patients exhibited dissimilarities compared to that in healthy subjects, which was distinguished by Prevotella, Slackia, Enterococcus, Bifidobacterium, and Lactobacillales may be potential markers for tracking the progression of hypertension, and Bifidobacterium, Butyricimonas, Adlercreutzia, Faecalibacterium, Lactobacillus, Ruminococcus, Clostridium, and Acidaminococcus demonstrated diagnostic value. Meanwhile, tracking the dynamic changes of deoxycholic acid, 4-oxododecanedioic acid, and l-arginine can serve as biomarkers for early diagnosis, and investigation into the mechanism by which the intestinal microbiome influences the onset and progression of hypertension. In terms of pathogenesis, the findings revealed that Bifidobacterium may caused the changes of AST, indirect bilirubin, ALT, triglyceride and uric acid by affecting metabolites cis-7-hexadecenoic acid methyl ester and N1-acetylspermidine. Additionally, Coprococcus may cause changes in albumin through the influence of androsterone enanthate.Conclusions. These findings highlight that the unique intestinal microbiome and serum metabolic profile in different periods of hypertension will provide valuable insight for timely diagnosis and prognosis tracking in hypertension patients with promising clinical applications.

Early and late gut microbiota signatures of stroke in high salt-fed stroke-prone spontaneously hypertensive rats.

The high salt-fed stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable tool to study the mechanisms underlying stroke pathogenesis. Salt intake modifies the gut microbiota (GM) in rats and humans and alterations of the GM have previously been associated with increased stroke occurrence. We aimed to characterize the GM profile in SHRSPs fed a high-salt stroke-permissive diet (Japanese diet, JD), compared to the closely related stroke-resistant control (SHRSR), to identify possible changes associated with stroke occurrence. SHRSPs and SHRSRs were fed a regular diet or JD for 4 weeks (short-term, ST) or a maximum of 10 weeks (long-term, LT). Stroke occurred in SHRSPs on JD-LT, preceded by proteinuria and diarrhoea. The GM of JD-fed SHRSPs underwent early and late compositional changes compared to SHRSRs. An overrepresentation of Streptococcaceae and an underrepresentation of Lachnospiraceae were observed in SHRSPs JD-ST, while in SHRSPs JD-LT short-chain fatty acid producers, e.g. Lachnobacterium and Faecalibacterium, decreased and pathobionts such as Coriobacteriaceae and Desulfovibrio increased. Occludin gene expression behaved differently in SHRSPs and SHRSRs. Calprotectin levels were unchanged. In conclusion, the altered GM in JD-fed SHRSPs may be detrimental to gut homeostasis and contribute to stroke occurrence.

Microbiota based personalized nutrition improves hyperglycaemia and hypertension parameters and reduces inflammation: a prospective, open label, controlled, randomized, comparative, proof of concept study.

Background: Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota through targeted nutrition can provide beneficial effects leading to the concept of personalized nutrition for health improvement. In this prospective clinical trial, we evaluated the impact of a microbiome-based targeted personalized diet on hyperglycaemic and hyperlipidaemic individuals. Specifically, BugSpeaks®-a microbiome profile test that profiles microbiota using next generation sequencing and provides personalized nutritional recommendation based on the individual microbiota profile was evaluated. Methods: A total of 30 participants with type 2 diabetes and hyperlipidaemia were recruited for this study. The microbiome profile of the 15 participants (test arm) was evaluated using whole genome shotgun metagenomics and personalized nutritional recommendations based on their microbiota profile were provided. The remaining 15 participants (control arm) were provided with diabetic nutritional guidance for 3 months. Clinical and anthropometric parameters such as HbA1c, systolic/diastolic pressure, c-reactive protein levels and microbiota composition were measured and compared during the study. Results: The test arm (microbiome-based nutrition) showed a statistically significant decrease in HbA1c level from 8.30 (95% confidence interval (CI), [7.74-8.85]) to 6.67 (95% CI [6.2-7.05]), p < 0.001 after 90 days. The test arm also showed a 5% decline in the systolic pressure whereas the control arm showed a 7% increase. Incidentally, a sub-cohort of the test arm of patients with >130 mm Hg systolic pressure showed a statistically significant decrease of systolic pressure by 14%. Interestingly, CRP level was also found to drop by 19.5%. Alpha diversity measures showed a significant increase in Shannon diversity measure (p < 0.05), after the microbiome-based personalized dietary intervention. The intervention led to a minimum two-fold (Log2 fold change increase in species like Phascolarctobacterium succinatutens, Bifidobacterium angulatum, and Levilactobacillus brevis which might have a beneficial role in the current context and a similar decrease in species like Alistipes finegoldii, and Sutterella faecalis which have been earlier shown to have some negative effects in the host. Overall, the study indicated a net positive impact of the microbiota based personalized dietary regime on the gut microbiome and correlated clinical parameters.

Toll-like receptor 4 mutation mitigates gut microbiota-mediated hypertensive kidney injury.

Hypertension-associated dysbiosis is linked to several clinical complications, including inflammation and possible kidney dysfunction. Inflammation and TLR4 activation during hypertension result from gut dysbiosis-related impairment of intestinal integrity. However, the contribution of TLR4 in kidney dysfunction during hypertension-induced gut dysbiosis is unclear. We designed this study to address this knowledge gap by utilizing TLR4 normal (TLR4N) and TLR4 mutant (TLR4M) mice. These mice were infused with high doses of Angiotensin-II for four weeks to induce hypertension. Results suggest that Ang-II significantly increased renal arterial resistive index (RI), decreased renal vascularity, and renal function (GFR) in TLR4N mice compared to TLR4M. 16 S rRNA sequencing analysis of gut microbiome revealed that Ang-II-induced hypertension resulted in alteration of Firmicutes: Bacteroidetes ratio in the gut of both TLR4N and TLR4M mice; however, it was not comparably rather differentially. Additionally, Ang-II-hypertension decreased the expression of tight junction proteins and increased gut permeability, which were more prominent in TLR4N mice than in TLR4M mice. Concomitant with gut hyperpermeability, an increased bacterial component translocation to the kidney was observed in TLR4N mice treated with Ang-II compared to TLR4N plus saline. Interestingly, microbiota translocation was mitigated in Ang-II-hypertensive TLR4M mice. Furthermore, Ang-II altered the expression of inflammatory (IL-1ß, IL-6) and anti-inflammatory IL-10) markers, and extracellular matrix proteins, including MMP-2, -9, -14, and TIMP-2 in the kidney of TLR4N mice, which were blunted in TLR4M mice. Our data demonstrate that ablation of TLR4 attenuates hypertension-induced gut dysbiosis resulting in preventing gut hyperpermeability, bacterial translocation, mitigation of renal inflammation and alleviation of kidney dysfunction.

Analysis of the gut microbiota profile targeted to multiple hypervariable regions of 16S rRNA in a hypertensive heart failure rat model.

The gut microbiota, comprising a diverse community of microorganisms, significantly influences various aspects of health. Changes in the composition of the gut microbiota are implicated in adverse effects on host physiology, contributing to the pathogenesis of cardiovascular diseases, among others pathological conditions. Understanding the role of the gut microbiota in the context of heart failure is particularly important. In this regard, the spontaneously hypertensive heart failure (SHHF) rat is an adequate experimental model since exhibits many features in common with heart failure (HF) in humans. Recent advancements in next-generation sequencing (NGS) have greatly improved microbiome analysis. However, standardization and the adoption of best practices are essential to mitigate experimental variations across studies. This manuscript outlines a straightforward methodology for analyzing gut microbiota composition in SHHF rat fecal samples using 16S rRNA sequencing, emphasizing the relevance of gut microbiota in heart failure.

The gut-immune axis during hypertension and cardiovascular diseases.

The gut-immune axis is a relatively novel phenomenon that provides mechanistic links between the gut microbiome and the immune system. A growing body of evidence supports it is key in how the gut microbiome contributes to several diseases, including hypertension and cardiovascular diseases (CVDs). Evidence over the past decade supports a causal link of the gut microbiome in hypertension and its complications, including myocardial infarction, atherosclerosis, heart failure, and stroke. Perturbations in gut homeostasis such as dysbiosis (i.e., alterations in gut microbial composition) may trigger immune responses that lead to chronic low-grade inflammation and, ultimately, the development and progression of these conditions. This is unsurprising, as the gut harbors one of the largest numbers of immune cells in the body, yet is a phenomenon not entirely understood in the context of cardiometabolic disorders. In this review, we discuss the role of the gut microbiome, the immune system, and inflammation in the context of hypertension and CVD, and consolidate current evidence of this complex interplay, whilst highlighting gaps in the literature. We focus on diet as one of the major modulators of the gut microbiota, and explain key microbial-derived metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide) as potential mediators of the communication between the gut and peripheral organs such as the heart, arteries, kidneys, and the brain via the immune system. Finally, we explore the dual role of both the gut microbiome and the immune system, and how they work together to not only contribute, but also mitigate hypertension and CVD.

Sleeve Gastrectomy Protects Against Hypertension in Rats due to Changes in the Gut Microbiome.

INTRODUCTION: Sleeve gastrectomy (SG), results in improvement in hypertension. We have previously published that rodent SG improves hypertension independent of weight loss associated with unique shifts in the gut microbiome. We tested if the gut microbiome directly improves blood pressure by performing fecal material transfer (FMT) from post-SG rats to surgery-naïve animals. METHODS: We performed SG or Sham surgery in male, Zucker rats (n = 6-7) with obesity. Stool was collected postop from surgical donors for treatment of recipient rats. Three nonsurgical groups received daily, oral consumption of SG stool, sham stool, or vehicle alone (Nutella) for 10 wk (n = 7-8). FMT treatment was assessed for effects on body weight, food intake, oral glucose tolerance, and blood pressure. Genomic deoxyribonucleic acid of stool from donor and recipient groups were sequenced by 16S ribosomal ribonucleic acid and analyzed for diversity, abundance, and importance. RESULTS: Ten weeks of SG-FMT treatment significantly lowered systolic blood pressures in surgery-naïve, recipient rats compared to vehicle treatment alone (126.8 ± 13.3 mmHg versus 151.8 ± 12.2 mmHg, P = 0.001). SG-FMT treatment also significantly altered beta diversity metrics compared to Sham-FMT and vehicle treatment. In random forest analysis, amplicon sequence variant level significantly predicted FMT group, P = 0.01. CONCLUSIONS: We have found a direct link between gut microbial changes after SG and regulation of blood pressure. Future mechanistic studies are required to learn what specific gut microbial changes are required to induce improvements in obesity-associated hypertension and translation to clinical, metabolic surgery.

Untapped potential of gut microbiome for hypertension management.

The gut microbiota has been shown to be associated with a range of illnesses and disorders, including hypertension, which is recognized as the primary factor contributing to the development of serious cardiovascular diseases. In this review, we conducted a comprehensive analysis of the progression of the research domain pertaining to gut microbiota and hypertension. Our primary emphasis was on the interplay between gut microbiota and blood pressure that are mediated by host and gut microbiota-derived metabolites. Additionally, we elaborate the reciprocal communication between gut microbiota and antihypertensive drugs, and its influence on the blood pressure of the host. The field of computer science has seen rapid progress with its great potential in the application in biomedical sciences, we prompt an exploration of the use of microbiome databases and artificial intelligence in the realm of high blood pressure prediction and prevention. We propose the use of gut microbiota as potential biomarkers in the context of hypertension prevention and therapy.

Salivary microbial shifting in hypertensive patients with chronic periodontitis after scaling and root surface debridement.

OBJECTIVES: This study aimed to evaluate the impact of scaling and root surface debridement (SRP) on salivary bacterial counts and systolic and diastolic blood pressure in hypertensive patients with chronic periodontitis, with a focus on clinical significance. METHODS: An observational trial included 24 chronic periodontitis patients, eleven of them were hypertensive patients. Non-surgical periodontal treatment was administered to all patients, with clinical parameters including gingival index (GI), plaque index (PI), and probing pocket depth (PPD) recorded. Saliva samples were collected before and after SRP to quantify total bacterial counts and specific bacterial counts. RESULTS: Two months following SRP, PI and PPD in every subject under study demonstrated good responses. In hypertension patients, the salivary bacterial count was significantly higher following SRP (P = 0.0221). The incidence of Porphyromonas gingivalis in hypertension patients significantly decreased after treatment (P = 0.0386). Despite this, there was no discernible decrease in blood pressure following treatment. CONCLUSIONS: SRP alone was ineffective in reducing overall bacterial counts, but P. gingivalis levels responded favorably. Regular periodontal assessment is crucial for hypertensive individuals to mitigate cardiovascular risk. CLINICAL SIGNIFICANCE: Periodontal therapy in hypertensive patients may improve oral health but might not significantly impact blood pressure. Regular periodontal evaluation is essential for managing cardiovascular risk in hypertension.

Exploring the relationship between gut microbiome modulation and blood pressure in type 2 diabetes: An umbrella review.

AIMS: Given the epidemic proportions of type 2 diabetes mellitus (T2DM) globally, it's crucial to comprehensively understand the factors influencing its management. The gut microbiome, known for its influence on various aspects of health, has emerged as a potential regulator of blood pressure in individuals with T2DM. This umbrella review aimed to consolidate the findings of existing meta-analyses investigating the impact of gut microbiome modulation on systolic and diastolic blood pressure in T2DM patients. DATA SYNTHESIS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we systematically searched PubMed, Scopus, and Web of Science databases from inception to July 2023. Quality assessment was performed using the AMSTAR2 and GRADE checklists. Statistical analyses were conducted using Comprehensive Meta-Analysis (CMA) version 3. A total of 6 meta-analyses meeting the inclusion criteria were included. The results revealed a significant association between microbial modulation and diastolic blood pressure (SMD: -0.133; 95% CI: -0.219 to -0.048; P = 0.002). However, the effect of gut microbial modulation on systolic blood pressure did not reach statistical significance (SMD: -0.077; 95% CI: -0.162 to 0.009; P = 0.078). CONCLUSION: This study found that modulating the gut microbiome had a statistically significant impact on diastolic blood pressure in individuals with type 2 diabetes mellitus (T2DM). However, no significant effect was observed on systolic blood pressure. While high-quality meta-analyses reported favorable outcomes, caution is warranted due to the low clinical importance, diversity in study populations, and variations in interventions.

Perspectives on the involvement of the gut microbiota in salt-sensitive hypertension.

Salt-sensitivity hypertension (SSH) is an independent predictor of cardiovascular event-related death. Despite the extensiveness of research on hypertension, which covers areas such as the sympathetic nervous system, the renin-angiotensin system, the vascular system, and the immune system, its pathogenesis remains elusive, with sub-optimal blood pressure control in patients. The gut microbiota is an important component of nutritional support and constitutes a barrier in the host. Long-term high salt intake can lead to gut microbiota dysbiosis and cause significant changes in the expression of gut microbiota-related metabolites. Of these metabolites, short chain fatty acids (SCFAs), trimethylamine oxide, amino acids, bile acids, and lipopolysaccharide are essential mediators of microbe-host crosstalk. These metabolites may contribute to the incidence and development of SSH via inflammatory, immune, vascular, and nervous pathways, among others. In addition, recent studies, including those on the histone deacetylase inhibitory mechanism of SCFAs and the blood pressure-decreasing effects of H2S via vascular activation, suggest that several proteins and factors in the classical pathway elicit their effects through multiple non-classical pathways. This review summarizes changes in the gut microbiota and its related metabolites in high-salt environments, as well as corresponding treatment methods for SSH, such as diet management, probiotic and prebiotic use, antibiotic use, and fecal transplantation, to provide new insights and perspectives for understanding SSH pathogenesis and the development of strategies for its treatment.

Genetic association between gut microbiome and blood pressure and blood cell count as mediator: A two-step Mendelian randomization analysis.

BACKGROUND: Previous studies have established a genetic link between gut microbiota and hypertension, but whether blood cell count plays a mediating role in this remains unknown. This study aims to explore genetic associations and causal factors involving the gut microbiome, peripheral blood cell count, and blood pressure. METHODS: We utilized summary statistics derived from genome-wide association studies to conduct a two-sample mediation Mendelian randomization analysis (https://gwas.mrcieu.ac.uk/). We applied inverse variance weighted (IVW) estimation method as the primary method, along with MR Egger, Weighted median, Simple mode and Weighted mode as complementary methods. To ensure the robustness of the results, several sensitivity analyses were conducted. RESULTS: Genetic variants significantly associated with the microbiome, blood pressure, or peripheral blood cell counts were selected as instrumental variables. Fourteen microbial taxa were found to have suggestive associations with diastolic blood pressure (DBP), while fifteen microbial taxa showed suggestive associations with systolic blood pressure (SBP). Meanwhile, red blood cell count, lymphocyte count, and platelet count were identified to mediate the influence of the gut microbiome on blood pressure. Specifically, red cell count was identified to mediate the effects of the phylum Cyanobacteria on DBP (mediated proportion: 8.262 %). Lymphocyte count was found mediate the effects of the genus Subdoligranulum (mediated proportion: 2.642 %) and genus Collinsella (mediated proportion: 2.749 %) on SBP. Additionally, platelet count was found to mediate the relationship between the genus Eubacterium ventriosum group and SBP, explaining 3.421 % of the mediated proportion. CONCLUSIONS: Our findings highlighted that gut microbiota may have causal influence on the blood pressure by modulating blood cell counts, which sheds new light on the pathogenesis and potential clinical interventions through the intricate axis of gut microbiome, blood cell counts, and blood pressure.

Altered gut microbiota and metabolite profiles provide clues in understanding resistant hypertension.

BACKGROUND: Resistant hypertension is a severe phenotype in hypertension that may be driven by interactions between genetic and environmental factors. Specific changes in gut microbiota and metabolites have been shown to influence cardiovascular disease progression. However, microbial and metabolomic changes associated with resistant hypertension remain elusive. METHODS: In this study, the gut microbiome of 30 participants with resistant hypertension, 30 with controlled hypertension, and 30 nonhypertension was characterized using 16S rRNA amplicon sequencing. In addition, the serum metabolome of the same population was assessed by untargeted metabolomics. RESULTS: The alpha diversity of microbiome in the resistant hypertension decreased, and changes were also observed in the composition of the gut microbiota. The resistant hypertension group was characterized by elevated levels of Actinobacteitia and Proteobacteria. Twenty-three genera were found to have significantly different abundances between resistant hypertension and controlled hypertension, as well as 55 genera with significantly different abundances between resistant hypertension and nonhypertension. Compared with the controlled hypertension group, the genera Rothia and Sharpea in resistant hypertension were more abundant. Compared with the nonhypertension group, the genera Escherichia-Shigella , Lactobacillus , Enterococcus were more abundant. Untargeted metabolomics provided distinctly different serum metabolic profiles for the three groups and identified a range of differential metabolites. These metabolites were mainly associated with the pathway of glycerophospholipid metabolism. Furthermore, correlation analysis provided evidence of new interactions between gut microbiota and metabolites in the resistant hypertension. CONCLUSION: In conclusion, our study provides a comprehensive understanding of the resistant hypertension gut microbiota and metabolites, suggesting that treatment resistance in resistant hypertension patients may be related to the gut microbiota and serum metabolites.

Differing contributions of the gut microbiota to the blood pressure lowering effects induced by first-line antihypertensive drugs.

BACKGROUND AND PURPOSE: This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. EXPERIMENTAL APPROACH: Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3 weeks. KEY RESULTS: Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects. CONCLUSIONS AND IMPLICATIONS: First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication.

The synchronized feature of Saururus chinensis and gut microbiota against T2DM, NAFLD, obesity and hypertension via integrated pharmacology.

Type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), obesity (OB) and hypertension (HT) are categorized as metabolic disorders (MDs), which develop independently without distinct borders. Herein, we examined the gut microbiota (GM) and Saururus chinensis (SC) to confirm their therapeutic effects via integrated pharmacology. The overlapping targets from the four diseases were determined to be key protein coding genes. The protein-protein interaction (PPI) networks, and the SC, GM, signalling pathway, target and metabolite (SGSTM) networks were analysed via RPackage. Additionally, molecular docking tests (MDTs) and density functional theory (DFT) analysis were conducted to determine the affinity and stability of the conformer(s). TNF was the main target in the PPI analysis, and equol derived from Lactobacillus paracasei JS1 was the most effective agent for the formation of the TNF complex. The SC agonism (PPAR signalling pathway), and antagonism (neurotrophin signalling pathway) by SC were identified as agonistic bioactives (aromadendrane, stigmasta-5,22-dien-3-ol, 3,6,6-trimethyl-3,4,5,7,8,9-hexahydro-1H-2-benzoxepine, 4α-5α-epoxycholestane and kinic acid), and antagonistic bioactives (STK734327 and piclamilast), respectively, via MDT. Finally, STK734327-MAPK1 was the most favourable conformer according to DFT. Overall, the seven bioactives from SC and equol that can be produced by Lactobacillus paracasei JS1 can exert synergistic effects on these four diseases.

Effects of fecal microbiota transfer on blood pressure in animal models: A systematic review and meta-analysis.

BACKGROUND: Numerous recent studies have found a strong correlation between intestinal flora and the occurrence of hypertension. However, it remains unclear whether fecal microbiota transfer might affect the blood pressure of the host. This study aimed to quantify both associations. METHODS: An electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu, Embase, and SinoMed to retrieve relevant studies. The final search was completed on August 22, 2022. Two authors independently applied the inclusion criteria, extracted data, and assessed the risk of bias assessment. All data were analyzed using RevMan 5.4. RESULTS: A total of 5 articles were selected for final inclusion. All studies were assessed as having a high risk of bias according to the SYRCLE risk of bias tool. The meta-analysis results showed that transplantation of fecal bacteria from the hypertensive model can significantly improve the host's systolic pressure (MD = 18.37, 95%CI: 9.74~26.99, P<0.001), and diastolic pressure (MD = 17.65, 95%CI: 12.37~22.93, P<0.001). Subgroup analyses revealed that the increase in systolic pressure in the hypertension model subgroup (MD = 29.56, 95%CI = 23.55-35.58, P<0.001) was more pronounced than that in the normotensive model subgroup (MD = 12.48, 95%CI = 3.51-21.45, P<0.001). CONCLUSION: This meta-analysis suggests a relationship between gut microbiota dysbiosis and increased blood pressure, where transplantation of fecal bacteria from the hypertensive model can cause a significant increase in systolic pressure and diastolic pressure in animal models.

Commensal microbiota regulate aldosterone.

The gut microbiome regulates many important host physiological processes associated with cardiovascular health and disease; however, the impact of the gut microbiome on aldosterone is unclear. Investigating whether gut microbiota regulate aldosterone can offer novel insights into how the microbiome affects blood pressure. In this study, we aimed to determine whether gut microbiota regulate host aldosterone. We used enzyme-linked immunosorbent assays (ELISAs) to assess plasma aldosterone and plasma renin activity (PRA) in female and male mice in which gut microbiota are intact, suppressed, or absent. In addition, we examined urinary aldosterone. Our findings demonstrated that when the gut microbiota is suppressed following antibiotic treatment, there is an increase in plasma and urinary aldosterone in both female and male mice. In contrast, an increase in PRA is seen only in males. We also found that when gut microbiota are absent (germ-free mice), plasma aldosterone is significantly increased compared with conventional animals (in both females and males), but PRA is not. Understanding how gut microbiota influence aldosterone levels could provide valuable insights into the development and treatment of hypertension and/or primary aldosteronism. This knowledge may open new avenues for therapeutic interventions, such as probiotics or dietary modifications to help regulate blood pressure via microbiota-based changes to aldosterone.NEW & NOTEWORTHY We explore the role of the gut microbiome in regulating aldosterone, a hormone closely linked to blood pressure and cardiovascular disease. Despite the recognized importance of the gut microbiome in host physiology, the relationship with circulating aldosterone remains largely unexplored. We demonstrate that suppression of gut microbiota leads to increased levels of plasma and urinary aldosterone. These findings underscore the potential of the gut microbiota to influence aldosterone regulation, suggesting new possibilities for treating hypertension.

Oral-to-rectum microbial transmission in orthopedic patients without a history of intestinal disorders.

The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%-9.37% of the rectal microbiota. Particularly, Streptococcus salivarius, Fusobacterium nucleatum, and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis, formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota.

Influence of angiotensin II on the gut microbiome: modest effects in comparison to experimental factors.

AIMS: Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations. METHODS AND RESULTS: We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and ß-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and ß-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%). CONCLUSION: Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.

Regulatory effect of gut microbes on blood pressure.

Hypertension is an important global public health issue because of its high morbidity as well as the increased risk of other diseases. Recent studies have indicated that the development of hypertension is related to the dysbiosis of the gut microbiota in both animals and humans. In this review, we outline the interaction between gut microbiota and hypertension, including gut microbial changes in hypertension, the effect of microbial dysbiosis on blood pressure (BP), indicators of gut microbial dysbiosis in hypertension, and the microbial genera that affect BP at the taxonomic level. For example, increases in Lactobacillus, Roseburia, Coprococcus, Akkermansia, and Bifidobacterium are associated with reduced BP, while increases in Streptococcus, Blautia, and Prevotella are associated with elevated BP. Furthermore, we describe the potential mechanisms involved in the regulation between gut microbiota and hypertension. Finally, we summarize the commonly used treatments of hypertension that are based on gut microbes, including fecal microbiota transfer, probiotics and prebiotics, antibiotics, and dietary supplements. This review aims to find novel potential genera for improving hypertension and give a direction for future studies on gut microbiota in hypertension.