Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

Önal, Emine Meltem; Afsar, Barış; Covic, Adrian; Vaziri, Nosratola D.; Kanbay, Mehmet

doi:10.1038/s41440-018-0144-z

Cited by 79 publications

(77 citation statements)

References 251 publications

(426 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a recent meta-analysis, the incidence of acute kidney injury in AIS patients reached up to 9.6%, and was associated with increased overall mortality rate ( 96 ), in-hospital mortality, and neurological deterioration ( 97 ). Uremic toxins are waste products of microbiota that can cross the intestinal blood–barrier because of increased gut permeability after AIS, and thus reach the systemic circulation ( 98 ). In support of a purported gut–brain–kidney axis, an experimental study demonstrated that rats affected by both acute kidney injury and AIS displayed neuronal loss; glial, macrophage, and microglial upsurge; and increased circulating IL-6 and IL-1β levels ( 99 ).…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

et al. 2020

View full text Add to dashboard Cite

The microbiota-gut-brain axis is considered a central regulator of the immune system after acute ischemic stroke (AIS), with a potential role in determining outcome. Several pathways are involved in the evolution of gut microbiota dysbiosis after AIS. Brain-gut and gut-brain signaling pathways involve bidirectional communication between the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, the enteric nervous system, and the immune cells of the gut. Alterations in gut microbiome can be a risk factor and may also lead to AIS. Both risk factors for AIS and gut-microbiome composition are influenced by similar factors, including diabetes, hypertension, hyperlipidemia, obesity, and vascular dysfunction. Furthermore, the systemic inflammatory response after AIS may yield liver, renal, respiratory, gastrointestinal, and cardiovascular impairment, including the multiple organ dysfunction syndrome. This review focus on biochemical, immunological, and neuroanatomical modulation of gut microbiota and its possible systemic harmful effects after AIS, as well as the role of ischemic stroke on microbiota composition. Finally, we highlight the role of gut microbiota as a potential novel therapeutic target in acute ischemic stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Microbiota is also involved in the CKD-related systemic complications such as cardiovascular diseases, uremic sarcopenia, and mineral bone disorders [ 8 , 9 , 10 ]. The effects along the gut-kidney axis mainly involve metabolic and immune pathways [ 1 , 11 , 12 ]. The microbiota presents both positive and negative metabolic effects, since it is responsible for producing beneficial metabolites in kidney diseases such as short-chain fatty acids [ 13 , 14 ] and harmful metabolites such as uremic toxins [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Germ-Free Conditions Modulate Host Purine Metabolism, Exacerbating Adenine-Induced Kidney Damage

Mishima

Ichijo

Kawabe

et al. 2020

Toxins

View full text Add to dashboard Cite

Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of germ-free conditions on purine metabolism and renal immune responses involved in the kidney damage. Germ-free mice showed higher expression levels of purine-metabolizing enzymes such as xanthine dehydrogenase, which converts adenine to a nephrotoxic byproduct 2,8-dihydroxyadenine (2,8-DHA). The germ-free mice also showed increased urinary excretion of allantoin, indicating enhanced purine metabolism. Metabolome analysis demonstrated marked differences in the purine metabolite levels in the feces of germ-free mice and mice with microbiota. Furthermore, unlike the germ-free condition, antibiotic treatment did not increase the expression of purine-metabolizing enzymes or exacerbate adenine-induced kidney damage. Considering renal immune responses, the germ-free mice displayed an absence of renal IL-17A expression. However, the adenine-induced kidney damage in wild-type mice was comparable to that in IL-17A-deficient mice, suggesting that IL-17A does not play a major role in the disease condition. Our results suggest that the enhanced host purine metabolism in the germ-free mice potentially promotes the conversion of the administered adenine into 2,8-DHA, resulting in exacerbated kidney damage. This further suggests a role of the microbiota in regulating host purine metabolism.

show abstract

“…Most Proteobacteria and some Firmicutes family produce pro-inflammatory uremic toxins [81, 82], while Lactobacilli produce anti-inflammatory mediators, including short-chain fatty acid (SCFA) and NO [83, 84]. SCFAs increase anti-inflammatory gut hormones, including GLP-1, GLP-2, and PYY from enteroendocrine cells [83].…”

Section: Gastrointestinal Tract and Bp Regulationmentioning

confidence: 99%

Hypertension as a Metabolic Disorder and the Novel Role of the Gut

Tanaka

Itoh

2019

Curr Hypertens Rep

View full text Add to dashboard Cite

Purpose of Review Hypertension is related to impaired metabolic homeostasis and can be regarded as a metabolic disorder. This review presents possible mechanisms by which metabolic disorders increase blood pressure (BP) and discusses the importance of the gut as a novel modulator of BP. Recent Findings Obesity and high salt intake are major risk factors for hypertension. There is a hypothesis of "salt-induced obesity"; i.e., high salt intake may tie to obesity. Heightened sympathetic nervous system (SNS) activity, especially in the kidney and brain, increases BP in obese patients. Adipokines, including adiponectin and leptin, and renin-angiotensin-aldosterone system (RAAS) contribute to hypertension. Adiponectin induced by a high-salt diet may decrease sodium/glucose cotransporter (SGLT) 2 expression in the kidney, which results in reducing BP. High salt can change secretions of adipokines and RAAS-related components. Evidence has been accumulating linking the gastrointestinal tract to BP. Glucagon-like peptide-1 (GLP-1) and ghrelin decrease BP in both rodents and humans. The sweet taste receptor in enteroendocrine cells increases SGLT1 expression and stimulates sodium/glucose absorption. Roux-en-Y gastric bypass improves glycemic and BP control due to reducing the activity of SGLT1. Na/H exchanger isoform 3 (NHE3) increases BP by stimulating the intestinal absorption of sodium. Gastrin functions as an intestinal sodium taste sensor and inhibits NHE3 activity. Intestinal mineralocorticoid receptors also regulate sodium absorption and BP due to changing ENaC activity. Gastric sensing of sodium induces natriuresis, and gastric distension increases BP. Changes in the composition and function of gut microbiota contribute to hypertension. A high-salt/fat diet may disrupt the gut barrier, which results in systemic inflammation, insulin resistance, and increased BP. Gut microbiota regulates BP by secreting vasoactive hormones and short-chain fatty acids. BPlowering effects of probiotics and antibiotics have been reported. Bariatric surgery improves metabolic disorders and hypertension due to increasing GLP-1 secretion, decreasing leptin secretion and SNS activity, and changing gut microbiome composition. Strategies targeting the gastrointestinal system may be therapeutic options for improving metabolic abnormalities and reducing BP in humans. Summary SNS, brain, adipocytes, RAAS, the kidney, the gastrointestinal tract, and microbiota play important roles in regulating BP. Most notably, the gut could be a novel target for treatment of hypertension as a metabolic disorder.

show abstract

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

Cited by 79 publications

References 251 publications

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

Gut Microbiota in Acute Ischemic Stroke: From Pathophysiology to Therapeutic Implications

Germ-Free Conditions Modulate Host Purine Metabolism, Exacerbating Adenine-Induced Kidney Damage

Hypertension as a Metabolic Disorder and the Novel Role of the Gut

Contact Info

Product

Resources

About