Jujube polysaccharides mitigated anemia in rats with chronic kidney disease: Regulation of short chain fatty acids release and erythropoietin production

Abstract Chronic kidney disease (CKD) affects 10–15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that are required to improve renal function remain unknown. The present study aims to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis that SCFAs play a critical role in delaying CKD progression. One hundred and twenty-seven patients with CKD and 63 healthy controls from China were enrolled in the present study. Butyrate, which is considered beneficial to humans, was almost three-times higher in healthy volunteers than that in CKD5 subjects (P=0.001). Moreover, the serum SCFA levels in controls were significantly higher than that in CKD patients (P<0.05), and the butyrate level among CKD5 patients (1.48 ± 0.60 μmol/l) was less than half of that in controls (3.44 ± 2.12 μmol/l, P<0.001). In addition, we observed an inverse correlation between butyrate level and renal function (P<0.05). A CKD rat model transplanted with microbiota obtained from CKD patients exhibited accelerated CKD progression via increased production of trimethylamine N-oxide (TMAO), which was reversed by supplementation with extra butyrate. Our results showed that SCFA levels were reduced in CKD patients and that butyrate supplementation might delay CKD progression.

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Kidneys and microbiota

Ukrainian Journal of Nephrology and Dialysis ◽

10.31450/ukrjnd.1(65).2020.07 ◽

2019 ◽

pp. 48-57

Author(s):

Zh. Semydotska ◽

I. Chernyakova ◽

O. Avdeyeva

Keyword(s):

Chronic Kidney Disease ◽

Fatty Acids ◽

Kidney Disease ◽

Intestinal Microbiota ◽

General Circulation ◽

Short Chain Fatty Acids ◽

Uremic Toxins ◽

Short Chain ◽

Intestinal Lumen ◽

Chain Fatty Acids

The review article analyzes the results of studies of the bi-directional relationship of the intestinal microbiota and kidneys, the so-called colorenal interactive axis of interaction. The intestinal microbiota is considered as a kind of organ that influences the brain, cardiovascular and immune systems, as well as the kidneys of the "host". Short-chain fatty acids (SCFA) formed in the colon as the result of microbial metabolism from plant components of dietary fiber and acting as ligands for the olfactory receptor, paired G-proteins in the kidneys are recognized as the markers of this symbiosis. With the help of modern omix technologies, the development of dysbiosis taking into account patients with chronic kidney disease (CKD) has been proved, which leads to the accumulation of precursors of uremic toxins, a decrease in the production of SCFA, which have nephroprotective properties and play a key role in energy homeostasis. Changes in the composition of the intestinal microbiota in CKD, an increase in the content of uremic toxins in the intestinal lumen contribute to the appearance of the “leaky” intestinal barrier syndrome, the movement of bacteria from the intestine into the general circulation, the development of systemic inflammation, oxidative stress, comorbidity, the progression of CKD, and an increase in mortality. Diets with restriction of protein and potassium quotas, violation of nutritional status lead to the development of dysbiosis in CKD. A decrease in the diet of vegetables and fruit causes the expansion of bacteria producing uricase and urease, which are enzymes in the formation of uremic toxins and reduce the number and variety of bacteria producing short-chain fatty acids. Potential targeted effects on the axis of “intestinal microbiota - chronic kidney disease” are being discussed: the use of a diet enriched in plant fibers, heat-treated, then chilled potatoes and rice as prebiotics (sources of resistant starch), nuts, plant seeds, and pro-, pre-, synbiotics, fecal transplantation. Most of the proposed interventions in the structure and functions of the microbiota are not dangerous, side effects are minimal.

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Short-chain fatty acids: a link between prebiotics and microbiota in chronic kidney disease

Future Microbiology ◽

10.2217/fmb-2017-0059 ◽

2017 ◽

Vol 12 (15) ◽

pp. 1413-1425 ◽

Cited By ~ 22

Author(s):

Marta Esgalhado ◽

Julie A Kemp ◽

Nagila RT Damasceno ◽

Denis Fouque ◽

Denise Mafra

Keyword(s):

Chronic Kidney Disease ◽

Fatty Acids ◽

Kidney Disease ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

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1138 – Short-Chain Fatty Acids Postpone the Progression of Chronic Kidney Disease Via Decreasing the Microbial Production of Tmao

Gastroenterology ◽

10.1016/s0016-5085(19)37405-0 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-241

Author(s):

Wang S. Qi

Keyword(s):

Chronic Kidney Disease ◽

Fatty Acids ◽

Kidney Disease ◽

Short Chain Fatty Acids ◽

Microbial Production ◽

Short Chain ◽

Chain Fatty Acids

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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

Frontiers in Pharmacology ◽

10.3389/fphar.2020.569402 ◽

2020 ◽

Vol 11 ◽

Author(s):

Maha Al-Asmakh ◽

Muhammad Umar Sohail ◽

Ola Al-Jamal ◽

Banan Mosaad Shoair ◽

Asmaa Yousef Al-Baniali ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Fatty Acids ◽

Renal Function ◽

Kidney Disease ◽

Gut Microbiome ◽

Plasma Levels ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Biochemical Indicators ◽

Chain Fatty Acids

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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The Human Microbiome in Chronic Kidney Disease: A Double-Edged Sword

Frontiers in Medicine ◽

10.3389/fmed.2021.790783 ◽

2022 ◽

Vol 8 ◽

Author(s):

Eman Wehedy ◽

Ibrahim F. Shatat ◽

Souhaila Al Khodor

Keyword(s):

Chronic Kidney Disease ◽

Fatty Acids ◽

Kidney Disease ◽

Human Microbiome ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dietary Interventions ◽

High Fiber ◽

Kidney Functions ◽

Chain Fatty Acids

Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin–angiotensin–aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis—a change in the microbial diversity—has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.

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Blood Pressure Abnormalities Associated with Gut Microbiota-Derived Short Chain Fatty Acids in Children with Congenital Anomalies of the Kidney and Urinary Tract

Journal of Clinical Medicine ◽

10.3390/jcm8081090 ◽

2019 ◽

Vol 8 (8) ◽

pp. 1090 ◽

Cited By ~ 2

Author(s):

Chien-Ning Hsu ◽

Pei-Chen Lu ◽

Chih-Yao Hou ◽

You-Lin Tain

Keyword(s):

Blood Pressure ◽

Fatty Acids ◽

Urinary Tract ◽

Kidney Disease ◽

Gut Microbiota ◽

Congenital Anomalies ◽

Early Life ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

Both kidney disease and hypertension can originate from early life. Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease (CKD) in children. Since gut microbiota and their metabolite short chain fatty acids (SCFAs) have been linked to CKD and hypertension, we examined whether gut microbial composition and SCFAs are correlated with blood pressure (BP) load and renal outcome in CKD children with CAKUT. We enrolled 78 children with CKD stage G1–G4. Up to 65% of children with CAKUT had BP abnormalities on 24 h ambulatory blood pressure monitoring (ABPM). CKD children with CAKUT had lower risk of developing BP abnormalities and CKD progression than those with non-CAKUT. Reduced plasma level of propionate was found in children with CAKUT, which was related to increased abundance of phylum Verrucomicrobia, genus Akkermansia, and species Bifidobacterium bifidum. CKD children with abnormal ABPM profile had higher plasma levels of propionate and butyrate. Our findings highlight that gut microbiota-derived SCFAs like propionate and butyrate are related to BP abnormalities in children with an early stage of CKD. Early assessments of these microbial markers may aid in developing potential targets for early life intervention for lifelong hypertension prevention in childhood CKD.

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The change of gut microbiota‐derived short‐chain fatty acids in diabetic kidney disease

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.24062 ◽

2021 ◽

Author(s):

Chenyu Zhong ◽

Zhiwei Dai ◽

Lingxiong Chai ◽

Lingping Wu ◽

Jianhui Li ◽

...

Keyword(s):

Fatty Acids ◽

Kidney Disease ◽

Gut Microbiota ◽

Diabetic Kidney Disease ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Diabetic Kidney ◽

Chain Fatty Acids

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Quantitative Reduction of Gut Microbiota-Derived Short-Chain Fatty Acids in Stool and Serum in Diabetic Kidney Disease

10.21203/rs.3.rs-378090/v1 ◽

2021 ◽

Author(s):

Chenyu Zhong ◽

Zhiwei Dai ◽

Lingxiong Chai ◽

Lingping Wu ◽

Jianhui Li ◽

...

Keyword(s):

Fatty Acids ◽

Kidney Disease ◽

Gut Microbiota ◽

Diabetic Kidney Disease ◽

Statistical Significance ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Diabetic Kidney ◽

Gas Chromatograph Mass Spectrometry ◽

Chain Fatty Acids

Abstract ObjectivesPrevious studies found the dysbiosis of intestinal microbiota in individuals with diabetic kidney disease (DKD),especially the decreased SCFA-producing bacteria. We aimed to investigate stool and serum short-chain fatty acids (SCFAs), gut microbiota-derived metabolites, in individuals with DKD and the correlations. MethodsA total of 30 participants with DKD, 30 participants with type 2 diabetes mellitus (DM) and 30 normal controls (NC) in HwaMei Hospital were recruited from 1/1/2018 to 12/31/2019. Participants with DKD were divided into low estimated glomerular filtration rate (eGFR) (eGFR<60ml/min, n=14) and high eGFR (eGFR≥60ml/min, n=16) subgroups. Stool and serum were measured for SCFAs with gas chromatograph-mass spectrometry.ResultsThe group with DKD showed markedly lower levels of fecal acetate, propionate and butyrate versus NC group (P<0.05), and the lowest fecal total SCFAs concentration among the the groups. The group with DKD also had a lower serum caproate concentration than that with diabetes (P<0.05). In the univariate regression analysis, fecal and serum acetate correlated with eGFR in the group with DKD (OR= 1.013, P=0.072; OR=1.017, P=0.032). The correlation between serum total SCFAs and eGFR showed statistical significance (OR= 0.019, P=0.024) unadjusted and a borderline significance (OR= 1.024, P =0.063) when adjusted for Hb and LDL. The decrease in serum acetate and total SCFAs were found of borderline significant correlation in both subgroups (P=0.055, P=0.050). ConclusionThis study provides evidence that in individuals with DKD, serum and fecal SCFAs levels (fecal level in particular) were lowered, and there was a correlation between lower SCFAs and a worsened renal function.

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