Role of gut microbiota‐derived metabolites on vascular calcification in CKD

Abstract

The interaction between gut microbiota and the host has gained widespread concern. Gut microbiota not only provides nutrients from the ingested food but also generates bioactive metabolites and signalling molecules to impact host physiology, especially in chronic kidney disease (CKD). The development of CKD, accompanied by changed diet and medication, alters the gut flora and causes the effect in distant organs, leading to clinical complications. Vascular calcification (VC) is an actively regulated process and a high prevalence of VC in CKD has also been linked to an imbalance in gut microbiota and altered metabolites. In this review, we focused on gut microbiota‐derived metabolites involved in VC in CKD and explained how these metabolites influence the calcification process. Correcting the imbalance of gut microbiota and regulating microbiota‐derived metabolites by dietary modification and probiotics are new targets for the improvement of the gut‐kidney axis, which indicate innovative treatment options of VC in CKD.

Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease

“… 74 This disproportionate amount of plasmatic uremic toxins prompts the production of free radicals in both renal cells and VSMC through oxidative stress and inflammation, causing tissue injury. 75 IS induces the expression of osteoblast‐specific proteins and aortic wall calcification and thickening in Dahl salt‐sensitive hypertensive rats. 76 In line, IS has been shown to promote a phenotypic switch of vascular smooth muscular cells (VSMC) from a contractile to an osteogenic phenotype.…”

“… 127 SCFA seems to contribute to the improvement of vascular phenotypes. 75 Some studies have shown immunomodulatory capacities of SCFA. Inflammatory cells such as neutrophils, macrophages, dendritic cells and T cells are responsive to SCFA treatment, in line with their anti‐inflammatory effects in a wide range of inflammatory diseases, and reduction of vascular calcification, 128 although studies in this field are still limited.…”

Contribution of Gut Microbiota-Derived Uremic Toxins to the Cardiovascular System Mineralization

“…Serum TMAO concentrations in animals fed with experimental diets: 7.0 µmol/L (fish), 1.0 µmol/L (casein) and 1.5 µmol/L (soy) More advanced atherosclerosis and more calcified atherosclerotic lesions in animals fed with fish protein Aortic wall mRNA expression of of several inflammatory markers (including CD36, IL6 and ICAM-1) significantly higher in animals fed with fish protein Clinical trial [85] Observational trial of 817 apparently healthy participants aged between 33 No association between baseline serum TMAO and any of the analyzed outcomes, including: Cardiac death, sudden cardiac death, first CV event, death from any cause for the whole group and among Black patients TMAO significantly associated with all above endpoints among Whites The difference in outcome between races despite comparable serum TMAO between respective groups 1 IS, pCS and TMAO concentrations in experiments comparable to average serum concentrations in uremic patients.…”

“…The most important substances identified to impact on the endothelial cells and VSMC, and to promote VC include: Advanced glycation end-products, PCS, IS and trimethylamine-N-oxide (TMAO); Pi and phosphaturic hormones (such as parathyroid hormone and phosphatonin FGF23 are also classified by some authors as uremic toxins) [29][30][31]. Since gut microbiota is the most important source of PCS, IS and TMAO, uremia-dependent or kidney disease-specific gut microbiota abnormalities (dysbiosis) may also contribute to VC [32,33].…”

Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases

“…By comparing the microbial community structures between lung and intestine bacteria, evidence reveals that members of lung and intestine bacteria can directly exchange through the lymph circulation [ 51 , 52 , 53 ]. Additionally, gut microbiota can produce various kinds of bioactive metabolites (such as butyrate, p-cresol sulfate, and indoles) to impact the host immune response and energy homeostasis [ 54 , 55 , 56 , 57 , 58 ]. The innate lymphoid cells (ILCs) derived from intestinal lamina propria have important action on host defense and inflammatory responses.…”