What Would You Like to Eat, Mr CKD Microbiota? A Mediterranean Diet, please!

In this review we elucidate the role of gut microbiota as the plausible missing link between food and health, focusing on chronic kidney disease (CKD). Microbiota, the microbial community harboured in the large intestine, is considered a symbiotic "supplementary organ". It contributes to digestion, mainly through two catabolic pathways: saccharolytic (fermentation) or proteolytic (putrefaction). It also interacts with host influencing immunity, metabolism, and health status. It is believed that a balanced healthy microbiota is primarily saccharolytic and diet has a deep effect on its composition. Mediterranean Diet, UNESCO "Intangible Cultural Heritage of Humanity", prevents cardiovascular and metabolic systemic diseases, thanks to the high supply of fibres and antioxidants. Mediterranean Diet also favours the prevalence of saccharolytic species, while Western Diet promotes the shift towards a proteolytic profile (dysbiosis). Emerging evidences highlight the association between a wide range of diseases and dysbiosis. In CKD a vicious circle exists, in which proteolytic-derived microbial metabolites (p-cresol and indoxyl sulphate), represent the main circulating uremic toxins: their accumulation worsens dysbiosis and promotes CKD progression. Gut microbiota shaping through non-pharmacologic nutritional treatments, based on Mediterranean Diet, represents an innovative approach in CKD, potentially restoring microbiota balance, ameliorating CKD conditions and slowing down disease progression

Microbiota metabolites: Pivotal players of cardiovascular damage in chronic kidney disease

Abstract In chronic kidney disease (CKD), cardiovascular (CV) damage is present in parallel which leads to an increased risk of CV disease. Both traditional and non-traditional risk factors contribute to CV damage in CKD. The systemic role of the microbiota as a central player in the pathophysiology of many organs is progressively emerging in the literature: the microbiota is indeed involved in a complex, bi-directional network between many organs, including the kidney and heart connection, although many of these relationships still need to be elucidated through in-depth mechanistic studies. The aim of this review is to provide evidence that microbiota metabolites influence non-traditional risk factors, such as inflammation and endothelial dysfunction in CKD-associated CV damage. Here, we report our current understanding and hypotheses on the gut-kidney and gut-heart axes and provide details on the potential mechanisms mediated by microbial metabolites. More specifically, we summarize some novel hypotheses linking the microbiota to blood pressure regulation and hypertension. We also emphasise the idea that the nutritional management of CKD should be redesigned and include the new findings from research on the intrinsic plasticity of the microbiota and its metabolites in response to food intake. The need is felt to integrate the classical salt and protein restriction approach for CKD patients with foods that enhance intestinal wellness. Finally, we discuss the new perspectives, especially the importance of taking care of the microbiota in order to prevent the risk of developing CKD and hypertension, as well as the still not tested but very promising CKD innovative treatments, such as postbiotic supplementation and bacteriotherapy. This interesting area of research offers potential complementary approaches to the management of CKD and CV damage assuming that the causal mechanisms underlying the gut-kidney and gut-heart axes are clarified. This will pave the way to the design of new personalized therapies targeting gut microbiota

Gut Microbiota, the Immune System, and Cytotoxic T Lymphocytes

Gut microbiota, the largest microbial community living in the human body, exerts a variety of metabolic, structural, and functional actions. In particular, it is essential for the full immune system development and maturation, as demonstrated by studies on germ-free animals, showing immune impairment at different levels. Gut microbiota shapes the immune responses by promoting immune tolerance toward food antigens and commensals in the steady state. This process is orchestrated by a complex network of both microbial and human cells and molecular mediators. Microbiota eubiosis is fundamental in establishing a correct balance between tolerance and immunity. Contrarily, microbiota dysbiosis is correlated with alterations in the immune balance, as evidenced in intestinal pathologies characterized by aberrant immune responses, such as inflammatory bowel disease and celiac disease, in which either break of tolerance against commensals or microbial dysbiosis is reported. On the other hand, a role for gut microbiota in stimulating the cytotoxic immune response in contexts of immunosuppression, like the ones featuring tumors and vaccinations, is emerging. The bifaceted role of gut microbiota in the delicate balance between tolerance and immunity could be exploited in order to develop pioneering therapeutic strategies, complementary to the pharmacological ones, thus representing a field worthy of further studies specifically focused on this topic

Intestinal Microbiota in Type 2 Diabetes and Chronic Kidney Disease

Purpose of the Review: Diabetes mellitus is a major cause of kidney disease [chronic kidney disease (CKD) and end-stage renal disease (ESRD)] and are both characterized by an increased risk of cardiovascular events. Diabetes and kidney disease are also commonly associated with a chronic inflammatory state, which is now considered a non-traditional risk factor for atherosclerosis. In the case of type 2 diabetes mellitus (T2DM), inflammation is mainly a consequence of visceral obesity, while in the case of CKD or ESRD patients on dialysis, inflammation is caused by multiple factors, classically grouped as dialysis-related and non-dialysis-related. More recently, a key role has been credited to the intestinal microbiota in the pathogenesis of chronic inflammation present in both disease states. While many recent data on the intestinal microbiota and its relationship to chronic inflammation are available for CKD patients, very little is known regarding T2DM and patients with diabetic nephropathy. The aim of this review is to summarize and discuss the main pathophysiological issues of intestinal microbiota in patients with T2DM and CKD/ESRD. Recent Findings: The presence of intestinal dysbiosis, along with increased intestinal permeability and high circulating levels of lipopolysaccharides, a condition known as “endotoxemia,” characterize T2DM, CKD, and ESRD on dialysis. The hallmark of intestinal dysbiosis is a reduction of saccharolytic microbes mainly producing short-chain fatty acids (SCFA) and, in the case of CKD/ESRD, an increase in proteolytic microbes that produce different substances possibly related to uremic toxicity. Summary: Dysbiosis is associated with endotoxemia and chronic inflammation, with disruption of the intestinal barrier and depletion of beneficial bacteria producing SCFAs. T2DM and CKD/ESRD, whose coexistence is increasingly found in clinical practice, share similar negative effects on both intestinal microbiota and function. More studies are needed to characterize specific alterations of the intestinal microbiota in diabetic nephropathy and to assess possible effects of probiotic and prebiotic treatments in this setting

Nutrients, Nutraceuticals, and Xenobiotics Affecting Renal Health

Chronic kidney disease (CKD) affects 8⁻16% of the population worldwide. In developed countries, the most important risk factors for CKD are diabetes, hypertension, and obesity, calling into question the importance of educating and acting on lifestyles and nutrition. A balanced diet and supplementation can indeed support the maintenance of a general health status, including preservation of renal function, and can help to manage and curb the main risk factors for renal damage. While the concept of protein and salt restriction in nephrology is historically acknowledged, the role of some nutrients in renal health and the importance of nutrition as a preventative measure for renal care are less known. In this narrative review, we provide an overview of the demonstrated and potential actions of some selected nutrients, nutraceuticals, and xenobiotics on renal health and function. The direct and indirect effects of fiber, protein, fatty acids, curcumin, steviol glycosides, green tea, coffee, nitrates, nitrites, and alcohol on kidney health are reviewed here. In view of functional and personalized nutrition, understanding the renal and systemic effects of dietary components is essential since many chronic conditions, including CKD, are related to systemic dysfunctions such as chronic low-grade inflammation

Dietary protein and nutritional supplements in conventional hemodialysis

Protein energy wasting (PEW) is a condition commonly occurring among patients with ESRD on hemodialysis. PEW is characterized by depletion of protein and energy stores and is caused by multiple factors related to chronic kidney disease, acute and chronic comorbidities and by renal replacement therapy itself. Anorexia is central in the pathogenesis of PEW; it is frequently observed in these patients whose protein and energy intakes are typically lower than guidelines recommendations. If untreated, PEW invariably leads to major complications, and may activate a vicious circle with further worsening of nutritional status. Dietary counseling and nutritional status monitoring play a key role in the prevention and treatment of PEW, since they allow an early identification of high risk patients, as well as the assessment of the response to nutritional intervention. Different nutritional approaches can be implemented following thorough nutritional counseling. These are chosen on the basis of patients' spontaneous dietary intake, severity of PEW and acute comorbidities. Initially, regular encounters with the dietitian allow patients to clarify doubts and strengthen basic concepts on nutrition to improve dietary intake and prevent PEW. When PEW is present or the patient is at high risk, the clinician may opt for the administration of oral intradialytic or daily supplements, aiming at increasing energy and protein intake, while in selected cases intradialytic parenteral nutrition may be used. This review addresses the main issues of nutritional status in ESRD patients on hemodialysis-its evaluation and monitoring, as well as at describing the available nutritional interventions

Microbiota issue in CKD: how promising are gut-targeted approaches?

In chronic kidney disease (CKD), the progressive decline in the renal excretory function leads to accumulation of urea and toxins in the blood. The CKD-associated dysbiosis of gut microbiota further contributes to uremia by increasing intestinal toxins production. Gut microbiota is involved in a complex network of human organs, mediated by microbial metabolites: in CKD, gut–heart and gut–brain axes may have a role in increased cardiovascular risk and neuropsychiatric disorders. While the cardiovascular toxicity of some microbial molecules is well known, their presumptive neurotoxicity needs to be confirmed by specific studies. In this review, we describe gut–heart and gut–brain axes in CKD, with an overview of the experimental and human studies characterizing CKD-associated gut microbiota, and we discuss the benefits coming from new approaches aimed at gut manipulation. Microbiota metabolism is emerging as a modifiable non-traditional risk factor in nephrology. In order to take advantage of this issue, it is necessary to consider the microbiota manipulation as part of the nutritional management of CKD. Integrating the low-protein nutritional approach with prebiotic, probiotic and synbiotic supplementation is a promising tool to control disease progression and comorbidities, though an extensive validation in large-scale clinical trials is still required