Roles of short-chain fatty acids in kidney diseases

Li, Ling-Zhi; Tao, Sibei; Ma, Liang; Fu, Ping

doi:10.1097/cm9.0000000000000228

Cited by 29 publications

(25 citation statements)

References 55 publications

(75 reference statements)

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“…SCFAs exert multiple beneficial effects on host homeostasis and aid in recovery from disease through their anti-inflammatory, immune-modulatory, and anti-oxidative properties ( Puddu et al, 2014 ; Li et al, 2017 ; Li et al, 2019 ). The three major SCFAs acetate, propionate, and butyrate perform important physiological functions: butyrate is the preferential energy source for the gut mucosa; propionate contributes to gluconeogenesis by the liver; and acetate is used in the biosynthesis of cholesterol and fatty acids by the host ( Louis and Flint, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Gum Acacia on the Composition of the Gut Microbiome and Plasma Levels of Short-Chain Fatty Acids in a Rat Model of Chronic Kidney Disease

et al. 2020

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Chronic kidney disease (CKD) may be fatal for its victims and is an important long-term public health problem. The complicated medical procedures and diet restrictions to which patients with CKD are subjected alter the gut microbiome in an adverse manner, favoring over-accumulation of proteolytic bacteria that produce ammonia and other toxic substances. The present study aimed to investigate the effect of GA on 1) the composition of the gut microbiome and 2) on plasma levels of short-chain fatty acids. Male Wister rats were divided into four groups (six each) and treated for 4 weeks based on the following: control, dietary adenine (0.75%, w/w) to induce CKD, GA in the drinking water (15%, w/v), and both adenine and GA. At the end of the treatment period, plasma, urine, and fecal samples were collected for determination of several biochemical indicators of renal function and plasma levels of short-chain fatty acids (SCFAs) as well as characterization of the gut microbiome. Dietary adenine induced the typical signs of CKD, i.e., loss of body weight and impairment of renal function, while GA alleviated these effects. The intestine of the rats with CKD contained an elevated abundance of pathogenic Proteobacteria, Actinobacteria, and Verrucomicrobia but lowered proportions of Lactobacillaceae belonging to the Firmicutes phylum. Plasma levels of propionate and butyrate were lowered by dietary adenine and restored by GA. A negative association (Spearman’s p-value ≤ 0.01, r ≤ 0.5) was observed between Firmicutes and plasma creatinine, urea, urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin. Phylum Proteobacteria on the other hand was positively associated with these markers while Phylum Bacteroidetes was positively associated with plasma SCFAs. In conclusion, the adverse changes in the composition of the gut microbiome, plasma levels of SCFAs, and biochemical indicators of renal function observed in the rats with CKD induced by dietary adenine were mitigated by GA. These findings are indicative of a link between uremia and the composition of the microbiome in connection with this disease. Dietary administration of GA to patients with CKD may improve their renal function via modulating the composition of their microbiome—a finding that certainly warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

The Effects of Gum Acacia on the Composition of the Gut Microbiome and Plasma Levels of Short-Chain Fatty Acids in a Rat Model of Chronic Kidney Disease

et al. 2020

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“…Hence, SCFAs produced by the microbiota can be present in portal, hepatic, peripheral blood, and feces [35][36][37]. Low levels of SCFAs in the blood and gastrointestinal system are implicated in diabetes and inflammatory disease [38,39].…”

Section: Short Chain Fatty Acids-the By-products Of Microbial Metabolismmentioning

confidence: 99%

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

Zaky

Glastras

Wong

et al. 2021

IJMS

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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.

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“…However, the receptors of acetate not totally protective for cardiovascular function are also reported. Olfr-78 (OR51E2 in humans), a mir-129-targeted receptor of SCFAs (mainly acetate and butyrate) expressed on the afferent arteriole, was reported to increase BP through mediating renin secretion and subsequent vasoconstriction ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

The Association Between Changes in Plasma Short-Chain Fatty Acid Concentrations and Hypertension in Children With Chronic Kidney Disease

Hsu

Lin

et al. 2021

Front. Pediatr.

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Background: Some children with chronic kidney disease (CKD) develop hypertension faster than others. This may be attributable to endothelial dysfunction, among other reasons. Short-chain fatty acids (SCFAs), that is, acetate, butyrate, and propionate, are known for reducing cardiovascular risks via preserving endothelial function. This study aimed to investigate the association between changes in plasma SCFA concentrations and in cardiovascular and endothelial parameters in children with CKD.Methods: In total, 105 children and adolescents who met the CKD criteria were enrolled in this study, and 65 patients aged >6 years were divided into two groups based on the ambulatory BP measurements. The parameters of plasma SCFAs, endothelial function and morphology, and echocardiography were examined at the index visit and followed up after 1 year.Results: We observed that 27.69% of 65 patients developed hypertension during the study period. Plasma acetate increased by 22.75 μM in the stable group (P < 0.001), whereas there was no change in the worsened BP group. The index higher plasma butyrate was positively correlated with worsened BP (adjusted odd ratio, 1.381; P = 0.013). At the follow-up, plasma butyrate decreased by 2.12 and 4.41 μM in the stable and worsened BP groups, respectively (P < 0.001). In 105 subjects, higher index plasma propionate was positively correlated with decreasing ejection fraction (adjusted odd ratio, 1.281; P = 0.046).Conclusions: Plasma acetate seemed to play a role in preventing hypertension in children with CKD. However, the index plasma propionate and butyrate concentrations seemed to imply the development of cardiovascular problems in our 1-year study.

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Roles of short-chain fatty acids in kidney diseases

Cited by 29 publications

References 55 publications

The Effects of Gum Acacia on the Composition of the Gut Microbiome and Plasma Levels of Short-Chain Fatty Acids in a Rat Model of Chronic Kidney Disease

The Effects of Gum Acacia on the Composition of the Gut Microbiome and Plasma Levels of Short-Chain Fatty Acids in a Rat Model of Chronic Kidney Disease

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

The Association Between Changes in Plasma Short-Chain Fatty Acid Concentrations and Hypertension in Children With Chronic Kidney Disease

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