Gut Microbiota Dysbiosis in Human Hypertension: A Systematic Review of Observational Studies

Frontiers in Cardiovascular Medicine

May 2021

DOI: 10.3389/fcvm.2021.650227

Citations:48

Influential Citations:2

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Adults with hypertension and normotensive controls; 17 observational studies (n=9,085) across multiple countries; stool samples analyzed for gut microbiota via 16S rRNA gene sequencing and/or metagenomic sequencing; quality assessed with Newcastle-Ottawa Scale (NOS); PRISMA-based systematic review; PROSPERO registration CRD42020212219.

Results

Hypertension is associated with gut microbiota dysbiosis, including decreased alpha diversity and altered microbial composition. Depletion of short-chain fatty acid-producing bacteria (Faecalibacterium, Roseburia, Ruminococcus, Bifidobacterium, Akkermansia) and overgrowth of certain Proteobacteria and Bacteroidetes are reported. Functional analyses show up-regulation of lipopolysaccharide biosynthesis, phosphotransferase system, and ABC transporters, with down-regulation of some amino acid metabolism. Fecal short-chain fatty acids (SCFAs) levels are increased, while plasma SCFAs are decreased in hypertension. Inflammation markers (e.g., TNF, IL-6) are elevated; gut microbiota interactions via GPCR pathways (e.g., GPR41, Olfr78) may influence blood pressure. Overall, findings support a role for gut microbiota dysbiosis in hypertension pathogenesis and point to microbial-based therapies or SCFA-targeted approaches as future directions, though results are heterogeneous and further research is needed.

Limitations

Limitations: Potential selection bias and lack of representativeness; variable hypertension definitions across studies; geographic concentration in China and the US; language restrictions (English/Chinese abstracts); many studies cross-sectional, limiting causal inferences; methodological heterogeneity (16S vs metagenomics) and unmeasured confounding (diet, medications).

Abstract

Introduction: Hypertension is one of the major risk factors to human health and human studies on association between gut microbiota and hypertension or blood pressure have received increased attention. In the present study, we aim to evaluate gut microbiota dysbiosis in human hypertension using a method of systematic review. Methods: PubMed, EMBASE, and Web of Science databases were searched until March 2021 to identify eligible articles. Additional articles were also identified by searching specific authors in this field. Inclusion criteria were observational studies based on stool samples with hypertension group and control group. Newcastle-Ottawa quality assessment scale (NOS) was used to assess the quality of the included studies. PROSPERO registration number: CRD42020212219. Results: A total of 17 studies enrolling 9,085 participants were included. Fifteen of the enrolled studies showed good quality and two studies showed fair quality based on NOS. We found alpha diversity in hypertension decreased significantly and microbial structure can be separated compared with control groups. Gut microbiota of hypertension showed depletion of short chain fatty acids (SCFAs) producers and over-growth of some Proteobacteria and Bacteroidetes members. Up-regulation of lipopolysaccharide biosynthesis, phosphotransferase system, ABC transporters, etc. and down-regulation of some amino acid metabolism, etc. in hypertension were reported. Fecal SCFAs levels increased and plasma SCFAs levels decreased in hypertension. Stronger microbial interactions in hypertension were seen. Conclusion: In conclusion, gut microbiota dysbiosis was observed in hypertension, including decreased diversity, altered microbial structure, compositional change of taxa, alterations of microbial function, nutritional and immunological factors, and microbial interactions. Poor absorption and high excretion of SCFAs may play an important role in the pathogenesis of hypertension. These findings may provide insights into etiology study and new microbial-based therapies of hypertension. Systematic Review Registration: PROSPERO database, identifier CRD42020212219. show less