Abstract
Chronic kidney disease (CKD) is a worldwide major health problem. Traditional risk factors for CKD are hypertension, obesity, and diabetes mellitus. Recent studies have identified gut dysbiosis as a novel risk factor for the progression CKD and its complications. Dysbiosis can worsen systemic inflammation, which plays an important role in the progression of CKD and its complications such as cardiovascular diseases. In this review, we discuss the beneficial effects of the normal gut microbiota, and then elaborate on how alterations in the biochemical environment of the gastrointestinal tract in CKD can affect gut microbiota. External factors such as dietary restrictions, medications, and dialysis further promote dysbiosis. We discuss the impact of an altered gut microbiota on neuroendocrine pathways such as the hypothalamus–pituitary–adrenal axis, the production of neurotransmitters and neuroactive compounds, tryptophan metabolism, and the cholinergic anti-inflammatory pathway. Finally, therapeutic strategies including diet modification, intestinal alpha-glucosidase inhibitors, prebiotics, probiotics and synbiotics are reviewed.
Highlights
Chronic kidney disease (CKD) is a major health problem with a high economic burden to healthcare systems all over the world [1,2,3], with a higher global prevalence (11–13%) than diabetes mellitus (8.2%) [3]
The number of microbial genes is at least 150-fold more than the human genome [26,27]. These microbes have an extensive impact on their host, mainly relating to metabolic pathways for energy harvesting and the production of short-chain fatty acids (SCFAs) and vitamins [26]; it has been suggested that intestinal microbiota should be considered as an additional organ of the body [22]
Hemodialysis is thought to exacerbate the CKD-induced injury of the intestinal epithelial barrier [19,23,35,90,91], which was in part due to bowel ischemia from intradialysis and post-dialysis hypotension, and bowel edema due to intradialysis fluid retention, which may be compounded by hypoalbuminemia [13]
Summary
Chronic kidney disease (CKD) is a major health problem with a high economic burden to healthcare systems all over the world [1,2,3], with a higher global prevalence (11–13%) than diabetes mellitus (8.2%) [3]. It is defined by the presence of a marker of kidney damage such as proteinuria or a reduced estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2 ) for at least three months [4]. These factors include pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, reduced albumin level, increased C-reactive protein level, reduced growth hormone-insulin like growth factor-1 axis activity, hyperactivation of the renin-angiotensin aldosterone system, and the promotion of insulin resistance [20]
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