Gut microbiota: a promising target against cardiometabolic diseases

Figures & data

Figure 1. Suggested influence of gut microbiota (GM) proteolysis and saccharolysis on host insulin resistance and inflammation. The breakdown of proteins (proteolysis) by GM is associated with lower short-chain fatty acid (SCFA) levels as well as increased detrimental metabolites such as imidazole propionate (ImP) from the breakdown of histidine and BCAA from mammalian muscle protein, which is associated with increased intestinal permeability. This results in higher insulin resistance, worsened glucose metabolism as well as increased inflammatory markers. GM fermentation of complex carbohydrates (saccharolysis) such as fibers is associated with increased production of beneficial compounds. Examples of these beneficial compounds are SCFA like propionate and butyrate, secondary bile acids, and lower levels of detrimental metabolites such as BCAA, leading to improved glucose control, lower insulin resistance, and a reduction in inflammation.

Table 1. Cardiometabolic effects of specific bacteria.

Phylum	Genus	Species	Metabolic effect	Cardiovascular effect	Model
Actinobacteria	Bifidobacterium		IA: hs-CRP [38]	A: ↓cholesterol [153]	Human [38], In vitro [153]
Bacteroidetes			A: High intestinal energy extraction [59]		Human [59]
Bacteroidetes	Bacteroides			IA: coronary artery disease [127]	Human [127]
Bacteroidetes	Bacteroides	B. vulgatus	A: insulin resistance [34]		Human [34]
Bacteroidetes	Prevotella		IA: hs-CRP [38]	IA: coronary artery disease [127]	Human [127]
Bacteroidetes	Prevotella	P. copri	A: insulin resistance [34]		Human [34]
Bacteroidetes	Porphyromonas	P. gingivalis		A: atherosclerosis	Human [101,102]
Firmicutes			A: High intestinal energy extraction [59]		Human [59]
Firmicutes	Ruminococcus		IA: hs-CRP [38]		Human [38]
Firmicutes	Faecalibacterium		IA: hs-CRP [38]		Human [38]
Firmicutes	Lactobacillus		IA: hs-CRP [38]		Human [38]
Firmicutes	Lactobacillus	L. plantarum		A: ↓cholesterol, ↓triglycerides [154]*, ↓TMAO, IA: atherosclerotic lesions [155]*, LDL-C [157]*	Mouse [154]*, [155]*, Human [157]*
Firmicutes	Lactobacillus	L. rhamnosus	A: ↓oxLDL, ↑SOD, ↓MDA, ↓TNF-α, ↓IL-6, ↓MCP-1, ↓IL-6 [156]	IA: atherosclerosis [156]*	Mouse [156]*
Firmicutes	Streptococcus		IA: hs-CRP [38]	A: ACVD [128]	Human [38]
Firmicutes	Faecalibacterium	F. prausnitzii	IA: hs-CRP, IL-17 [38], T2DM [10]	IA: ACVD [128]	Human [10,38,128]
Firmicutes	Clostridium		A: IL-5, IL-17 [38]		Human [38]
Firmicutes	Roseburia	R. intestinalis	IA: T2DM [10], A: ↓VCAM-1, ↓TNF-α [130]	IA: ACVD [128], atherosclerotic lesions [130]	Human [10,128], Mouse [130]
Firmicutes	Roseburia	R. inulinivorans	IA: T2DM [10]		Human [10]
Firmicutes	Eubacterium	E. rectale	IA: T2DM [10]		Human [10]
Proteobacteria	Escherichiaa	E. coli		A: ACVD [128]	Human [128]
Proteobacteria	Klebsiella	K. pneumoniae		A: ACVD [128]	Human [128]
Proteobacteria	Klebsiella	K. aerogenes		A: ACVD [128]	Human [128]
Verrucomicrobia	Akkermansia	A. muciniphila	IA: T2DM [158]*, A: ↓macrophage infiltration, ↓MCP-1, ↓ICAM-1,↓TNF-α, ↓IL-1 [159]*, fat mass, ↓ fat mass, ↓insulin resistance, ↓triglycerides, ↓LDL, ↓ endotoxemia [158]*, [160]*, ↑insulin sensitivity, ↓total cholesterol, ↓insulinemia↓, ↓body weight [161]*	IA: atherosclerotic lesions [159]*	Human [161]*, Mouse [158]*, [159]*, [160]*
Phylum	Family	Species	Metabolic effect	Cardiovascular effect	Model
Firmicutes	Ruminococcaceae		IA: hs-CRP, IL-6 [38]		Human [38]
Phylum	Order	Species	Metabolic effect	Cardiovascular effect	Model
Firmicutes	Lactobacillales			A: coronary artery disease [127]	Human [127]

A: Association, IA: inverse association, ↑increased, ↓: decreased, IL: interleukin, ICAM-1: intracellular adhesion molecule 1, MDA: Malondialdehyde, MCP-1:monocyte chemoattractact-1, SOD: superoxide dismutase, VCAM-1: vascular cell adhesion molecule 1, *Probiotic intervention study.

Figure 2. Simplified overview of gut microbiota (GM)  contribution to the development of cardiometabolic diseases based on available animal and human studies. High-fat diet or diets rich in meat and eggs are associated with dysbiosis and have been shown to disrupt the intestinal barrier, this way, bacteria-derived endotoxins such as lipopolysaccharides (LPS), trimethylamine N-oxide (TMAO), and imidazole propionate (ImP) can enter the portal and systemic circulation. Circulating LPS induces systemic inflammation and inflammation of adipose tissue, which is associated with insulin resistance in the liver and muscle tissue, facilitating the onset of type 2 diabetes mellitus (T2DM). T2DM subjects have altered GM compositions, also called dysbiosis. T2DM patients with dysbiosis have an increased intestinal permeability, resulting again in endotoxemia. Inflammation, T2DM, and GM-derived metabolites have been associated with the development of atherosclerosis and can also influence thrombus growth.

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