The Role of the Gut Microbiome in Diabetes and Obesity-Related Kidney Disease

Abstract

Diabetic kidney disease (DKD) is a progressive disorder, which is increasing globally in prevalence due to the increased incidence of obesity and diabetes mellitus. Despite optimal clinical management, a significant number of patients with diabetes develop DKD. Hence, hitherto unrecognized factors are likely to be involved in the initiation and progression of DKD. An extensive number of studies have demonstrated the role of microbiota in health and disease. Dysregulation in the microbiota resulting in a deficiency of short chain fatty acids (SCFAs) such as propionate, acetate, and butyrate, by-products of healthy gut microbiota metabolism, have been demonstrated in obesity, type 1 and type 2 diabetes. However, it is not clear to date whether such changes in the microbiota are causative or merely associated with the diseases. It is also not clear which microbiota have protective effects on humans. Few studies have investigated the centrality of reduced SCFA in DKD development and progression or the potential therapeutic effects of supplemental SCFAs on insulin resistance, inflammation, and metabolic changes. SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. In this review, we will summarize the complex relationship between the gut microbiota and the kidney, examine the evidence for the role of gut dysbiosis in diabetes and obesity-related kidney disease, and explore the mechanisms involved. In addition, we will describe the role of potential therapies that modulate the gut microbiota to prevent or reduce kidney disease progression.

Cross-Talk between the Cytokine IL-37 and Thyroid Hormones in Modulating Chronic Inflammation Associated with Target Organ Damage in Age-Related Metabolic and Vascular Conditions

“…Conversely, the presence of metabolic disorders, as we have already stated above, can accelerate aging via the release of a wide range of molecules that serve as danger signals and can become augmented [ 11 , 12 , 14 , 92 ]. In addition, intestinal dysbiosis usually accompanies obesity and T2D, representing a large source of microbial signals; in this way, and owing to insufficient synthesis of some essential nutrients, this condition may contribute to persisting inflammation [ 13 , 93 ]. A better understanding of mechanisms that operate at the crossroads between the innate immune system and metabolic disorders could enable us to develop improved therapies for curing chronic inflammatory and metabolic disorders.…”

“…Many specific metabolites that alter the tolerance/inflammation balance by upregulating either FOXP3 or RORγt expression have been identified [ 99 ]. A tolerogenic response is promoted, for example, when short-chain FFAs are processed by commensals in the colon [ 93 ]. This usually occurs in situations when an individual is in good health and in the absence of metabolic disturbances such as obesity or T2D [ 102 ].…”

Urolithins: Diet-Derived Bioavailable Metabolites to Tackle Diabetes

“…Moreover, they stimulate the secretion of glucagon-like peptide (GLP) -1 and -2, adiponectin, and insulin [74,75]. Therefore, SCFAs at low levels in the blood and gastrointestinal tract are associated with diabetes-related dysbiosis [76].…”

Brief Overview of Dietary Intake, Gut Microbiota, Metabolic Markers and Research Opportunities in Sample of Egyptian Women

“…Firmicutes, due to their negative in uence on glucose and fat metabolism, are commonly referred to as bad gut microbes [10]. Accumulating evidence proved that short chain fatty acids (SCFA) play a critical role in supporting the intestine and metabolic health.…”