Research Progress on the Correlation Between Hypertension and Gut Microbiota

Figures & data

Table 1 Studies on Gut Microbiota Composition in Hypertension

Refs.	Study Subjects	Sequencing Method	Upregulate or Downregulate Microorganism phylum and Microorganism Genus
Qin et al^Citation13 (2022)	China population	/	Bacteroidetes↓: Bacteroidetes↓ Firmicutes↑↓: Firmicutes↑, Genus Megasphaera↑, Faecalibacterium↓, Roseburia↓, Ruminococcus↓ Proteobacteria↑: Escherichia_Shigella↑, Klebsiella↑ Actinobacteria↓: genus Bifidobacterium↓
Mushtaq et al^Citation14 (2019)	China population	High-throughput sequencing	Bacteroidetes↑↓: Prevotella_9↑, Bacteroides↓ Firmicutes↑↓: Megasphaera↑, Faecalibacterium↓ Proteobacteria↑↓: Parasutterella↑, Escherichia-Shigella↑
Yan et al^Citation15 (2020)	Rats	16S	Bacteroidetes↓: Bacteroidetes↓ Firmicutes↑: Firmicutes↑ Proteobacteria↑: Proteobacteria↑ Actinobacteria↑: Actinobacteria↑
Dinakis et al^Citation16 (2022)	Adult Australia population	16S	Bacteroidetes↑: Prevotella spp↑, Alistipes spp↑ Firmicutes↑: Clostridium spp↑, Lactobacillus spp↓, Gut microbial richness and evenness ↓
Han et al^Citation17 (2021)	SHR	16S/HPLC System	Bacteroidetes↑: Prevotella_9↑ Firmicutes↑: Phascolarctobacter↑
Fang et al^Citation18 (2022)	China patients with hypertension hospitalized	Metagenomic sequencing data	Bacteroidetes↑: Prevotella↑
Li et al^Citation19 (2019)	Rural areas of Henan, China	16S	Firmicutes↓: Clostridium perfringens 1↓, Romboutsia↓, Ruminococcus 2↓ Proteobacteria↓: Intestinibacter↓
Galla et al^Citation20 (2020)	Dahl salt‐sensitive rats	16S	Bacteroidetes↑: Prevotella↑ Firmicutes↑↓: Ruminococcus↑, Clostridium↑, Dorea↑, Veillonellaceae↑, Lachnospiraceae↑, Blautia↓ Proteobacteria↑↓: Pseudomonas↑; Sutterella↓ Actinobacteria↓: genuses Bifidobacterium↓
Dan et al^Citation21 (2019)	Adult China population	16S	Firmicutes↓: Clostridium perfringens 1↓, Romboutsia↓, Ruminococcus 2↓ Proteobacteria↓: Intestinibacter↓
Yan et al^Citation22 (2017)	Adult China population	Whole-metagenome shotgun sequencing	Bacteroidetes↑: Parabacteroides↑ Firmicutes↓: Clostridium↓, Streptococcus↓, Faecalibacterium↓, Roseburia↓ Proteobacteria↑: Klebsiella↑, Salmonella↑ Actinobacteria↑: Eggerthella↑
Su et al^Citation23 (2018)	China patients with hospitalized	/	Proteobacteria↑: Escherichia coli↑, Salmonella↑, Shigella↑
Lakshmanan et al^Citation24 (2021)	Childhood	16S	Actinobacteria↓: Bifidobacteria↓

Abbreviations: 16S, 16S rRNA sequencing; HPLC System, High-Performance Liquid Chromatography System; SHR, spontaneous hypertensive rats.

Figure 1 Effect of metabolites of gut microbiota on hypertension.

Notes: In Figure 1, the SCFA pathway, the TMAO pathway, and the LPS pathway are indicated by different coloured arrows, respectively. Created with BioRender.com.

Abbreviations: SCFA, short-chain fatty acid; TMA, trimethylamine; FMO3, flavin-containing monooxygenase 3; TMAO, trimethylamine N-oxide; LPS, lipopolysaccharide; Gpr41, G-protein coupled receptor 41; Olfr78, olfactory receptor 78.

Figure 2 Interaction between sympathetic activation and the gut-brain axis.

Note: Created with BioRender.com.

Abbreviations: PVN, paraventricular nucleus; NTS, nucleus of the solitary tract; RVLM, rostral ventrolateral medulla; NE, norepinephrine; TH, tyrosine hydroxylase.

Table 2 The Effect of Exercise on Gut Microbes

Refs.	Study Subjects	Sequencing Method	Microbiota Changes	Intervention methods	Post-Intervention Impact
Barton et al^Citation25 (2018)	Professional international rugby union players	HILIC chromatography profiling	Athletes excreted proportionately higher levels of the metabolite SCFA, TMAO	/	Fitness and overall health contribute to gut microbial diversity.
Kulecka et al^Citation26 (2020)	Polish elite athletes (endurance sports)	16S	Prevotella, and Veillonella genus ↑	/	Increase the diversity of gut microbes and optimize the structure of gut microbes.
Zhong et al^Citation27 (2022)	Elderly women	16S	Alpha diversity; members of the order Coriobacteriales; Asaccharobacter, Collinsella and Fusicatenibacter↑; risk of metabolic syndrome↓	8-week exercise training	Regulate the structure of gut microbes, reduce the risk of CVD, and enhance physical functions.
Wu et al^Citation28 (2023)	Middle-aged and elderly people in China	16S	BP and heart rate levels ↓, immune-inflammatory factors (IL-6, IL-10) ↓, F/B ratio ↓, abundance of Escherichia-Shigella ↓, Bacteroides ↑	12 weeks of LZJ training.	Improvement of inflammation and structure of the gut microbiota

Abbreviations: SCFA, Short-chain fatty acids; TMAO, Trimethylamine N-oxide; 16S, 16S rRNA sequencing; CVD, Cardiovascular Disease; IL-6, Interleukin-6; IL-10, Interleukin-10; F/B, Firmicutes/Bacteroidetes ratio; LZJ, Liuzijue.

Table 3 The Effect of Diet on Gut Microbes

Refs.	Study Subjects	Sequencing Method	Microbiota Changes	Intervention Methods	Post- Intervention Impact
Le et al^Citation60 (2022)	Healthy prehypertensive men and women aged 40–70 years, London	SMSeq	Gut microbiome gene richness and abundance of butyrate-producing species (eg, Lawsonibacter asaccharolyticus, Intestinimonas butyriciproducens) ↑	Aronia berry (poly)phenol	Improved vascular function in middle-aged people with prehypertension.
David et al^Citation94 (2014)	Healthy adults	16S/GC	Beta diversity, bile-tolerant microbes (Alistipes, Bilophila, Bacteroides) ↑; SCFAs, Firmicutes metabolizing plant polysaccharides (Roseburia, E. rectale, R. bromii)↓	Animal-based diet	A changed diet might cause the gut microbiome to adapt quickly.
Wan et al^Citation95 (2020)	China healthy adults	16S	Bacteroides, Clostridium, Bifidobacterium and Lactobacillus↑	High fat intake for 6 months	Alter the composition of intestinal microbiota, and damage colonic and cardiac metabolic health.
Cho^Citation96 (2021)	Korean children (aged 7 to 18 years)	16S	In the fat loss group: Firmicutes phylum, Clostridia class↑, Bacteroidetes phylum and microbial richness↓ In fat gain group: Firmicutes phylum, Clostridia class, Lachnospiraceae family, and Eubacterium hallii group genus↓	Lifestyle modifications	After weight loss, lifestyle adjustments alter the composition, diversity, and predicted functions of gut microbiota in obese children.
Andújar et al^Citation97 (2022)	6 weeks old male mice	16S	Butter group: Proteobacteria, Desulfovibrionaceae family↑, Lactobacillus↓ Extra virgin olive oil group: Desulfovibrionaceae family, Bacteroides finegoldii↑, Lactobacillus↓	Standard diet or one of two high fat diets containing either butter or extra virgin olive oil	Changes in the structure of the gut microbiota as a result of diet.
Vileigas et al^Citation98 (2019)	Male Wistar rats (60 days old)	/	/	CD, WDF, or WDS for 41 weeks.	Both WDF and WDS notably increased obesity and BP, with WDF also causing mild cardiac systolic dysfunction.
Filippou et al^Citation99 (2020)	Adults with and without Hypertension	/	/	DASH	DASH significantly reduced SBP and DBP, regardless of baseline BP.
Li et al^Citation100 (2020)	Spanish PREDIMED cohort and US NHS/HPFS cohort	HT LC-MS/MS	/	MD	A metabolome favoring healthy cardiometabolism ↑
Schwingshackl et al^Citation101 (2019)	Hypertensive and pre-hypertensive adult patients	/	/	DASH, Low-Fat, and 13 other diets	DASH diet was most effective in reducing SBP and DBP.
Jennings et al^Citation102 (2019)	Elderly people in Europe	/	/	MD	Sex differences: Males only responded to SBP and pulse pressure; females showed arterial stiffness effects, not peripheral BP.
Nagpal et al^Citation103 (2018)	Healthy adult female cynomolgus macaques	16S	Bacteroides, Proteobacteria, Fibrobacteres, Spirochaetes, Clostridiaceae, Lactobacillus, Faecalibacterium, Oscillospira ↑ Firmicutes and Verrucomicrobia; F/B ↓	MD	There were significant changes in the metabolome, improving cardiac metabolic health.
Belanger et al^Citation104 (2023)	Adults with elevated BP or hypertension	/	/	12 weeks of the DASH diet	DASH gradually decreased hs-cTnI and hs-CRP, potentially reducing subclinical heart injury.

Abbreviations: SMSeq, Shotgun metagenomics sequencing; 16S, 16S rRNA sequencing; GC, Gas chromatography; SCFA, Short-chain fatty acids; LC-MS/MS, Liquid Chromatography-Tandem Mass Spectrometry; hs-CRP, high-sensitivity C-reactive protein; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; CD, Control diet; WDF, Western diet fat; WDS, Western diet sugar; BP, blood pressure; DASH, Dietary Approaches to Stop Hypertension; HT LC-MS/MS, High-throughput liquid chromatography-tandem mass spectrometry; MD, Mediterranean diet; WD, Western diet; F/B, Firmicutes / Bacteroidetes ratio; hs-cTnI, high‐sensitivity cardiac troponin I.

Figure 3 Effects of exercise, dietary pattern, and treatment on hypertension.

Notes: In Figure 3, the anti-hypertensive pathway and the pathway leading to hypertension are indicated by blue and red arrows, respectively. Created with BioRender.com.

Abbreviations: MD, Mediterranean diet; DASH, Dietary Approaches to Stop Hypertension; FMT, fecal microbiota transplantation; WD, Western diet.

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