Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease

2019 ◽  
Vol 133 (17) ◽  
pp. 1857-1870 ◽  
Author(s):  
Siqi Wang ◽  
Dan Lv ◽  
Shuanghong Jiang ◽  
Jianpin Jiang ◽  
Min Liang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Renal Function ◽  
Kidney Disease ◽  
Critical Role ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
High Morbidity ◽  
Ckd Progression ◽  
Chain Fatty Acids

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.

scholarly journals 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

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.

scholarly journals Kidneys and microbiota

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.

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

2017 ◽  
Vol 12 (15) ◽  
pp. 1413-1425 ◽  
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

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

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.

scholarly journals Microbiota-Derived Short-Chain Fatty Acids Promote LAMTOR2-Mediated Immune Responses in Macrophages

mSystems ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Ting Wu ◽  
Hongru Li ◽  
Cong Su ◽  
Fangming Xu ◽  
Guangwei Yang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Survival Rates ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
High Morbidity ◽  
Content Type ◽  
Erk Phosphorylation ◽  
Dependent Signal ◽  
Chain Fatty Acids

ABSRTACT Klebsiella pneumoniae is a common cause of human-pneumonia-derived sepsis with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis. The mechanisms by which the gut microbiota affects the host defenses in the respiratory system systematically, however, remain poorly understood. Here, we show that gut microbiota depletion increases susceptibility to extracellular K. pneumoniae infections in terms of increased bacterial burdens in lung and decreased survival rates. Oral supplementation with gut microbiota-derived short-chain fatty acids (SCFAs), subsequently activating G protein-coupled receptor 43 (GPCR43), enhances a macrophage’s capacity to phagocytose invading K. pneumoniae. Furthermore, SCFAs and GPR43 increase macrophage bacterial clearance by upregulating LAMTOR2, which is further identified as an antibacterial effector and elucidated to facilitate phagosome-lysosome fusion and extracellular signal-regulated kinase (ERK) phosphorylation. Lastly, conditional ablation of Lamtor2 in macrophages decreases their antimicrobial activity, even though mice were pretreated with exogenous SCFA supplementation. IMPORTANCE These observations highlight that SCFAs promote macrophage elimination of K. pneumoniae via a LAMTOR2-dependent signal pathway and suggest that it is possible to intervene in K. pneumoniae pneumonia by targeting the gut microbiota.

scholarly journals MO046MICROBIOTA DERIVED SHORT CHAIN FATTY ACIDS, PROPIONATE AND BUTYRATE, CONTRIBUTE TO MODULATE THE INFLAMMATORY RESPONSE IN CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Viviana Corte ◽  
Ana Cristina Andrade ◽  
Paula Diaz-Bulnes ◽  
Nuria Salazar Garzo ◽  
Jose Joaquin Bande ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Renal Function ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Short Chain Fatty Acids

Abstract Background and Aims Dysbiosis, or changes in the gut microbiota composition, had been related to the developed of several pathologies, such as chronic kidney disease. Until now, multiple studies have focused on the influence of diet on outcomes of patients with CKD. These patients with advanced disease are recommended a restricted intake of vegetable fiber due to the phosphorus and potassium levels, and low proteins to avoid the generation of uremic toxins. It is known that dietary changes lead to alterations in gut microbiota, but also in microbial metabolites production, some of which could be beneficial for the host. A recent and exciting area of research has begun to explore the role of microbiota-derived metabolites in the renal physiology. Short-chain fatty acids (SCFA, acetate, propionate and butyrate) are a type metabolite produced from dietary fiber by gut microbiota that enter in the bloodstream leading to distal effects, such as modulation of the immune cells. SCFAs are essential to maintain the permeability of the intestinal epithelial barrier, the metabolic functions and have potent anti-inflammatory effects. The aim of this study was to identify the SCFAs levels during the progression of CKD and determinate the functional role of these metabolites in the renal inflammation. Method SFCAs (acetate, propionate and butyrate) levels were determined using gas chromatography-mass spectrometry in fecal samples collected from patients with different stages of CKD (n=60) and age-matched healthy control (n=20). Moreover, common bacterial families were determined by quantitative PCR. Additionally, the in-vitro effect of the three SCFAs was evaluated in the human tubular epithelial cell line HK2 using RNA-seq, specific silencing with siRNAs and histone deacetylases (HDAC) inhibitors. To evaluate the effect in immune cells, monocyte and macrophages were treated with LPS and ATP /Nigericin to induce inflammasome activation. Results The SCFAs levels were significantly lower in patients with CKD than in healthy controls, mainly propionate and butyrate. Moreover, these levels progressively decreased with the developed of the disease, showing the patients with stage 5 (CKD5) have the lowest levels that correlates with a lesser abundance of Clostridium IV family. According to the renal function, butyrate levels were positively correlated with the glomerular filtration rate and negatively with the blood urea nitrogen and creatinine levels. Surprisingly, high propionate levels correlate with the most elevated serum calcidiol concentrations. Functionally, propionate and butyrate show a similar pattern in the modulation of inflammatory genes in HK2 cells. Most regulated pathways are associated with Inflammatory response (GO:0006954: IL6, TNF, CCL2, RELB, IRAK2, NFKB1,CCL20) and immune response (GO:0006955: CSF2, CXCL3, CD40, IL7R, LIF). Additionally, both SCFAs regulates the expression of multiple epigenetic enzymes involves in the chromatin remodeling, mainly in histone acetylation. In monocytes/macrophages, propionate and butyrate inhibits the IL1B, CASP, and ASC gene transcription damaging the IL-1β secretion. We determined that the effect of SCFAs in these in-vitro models is mediated by inhibition of HDAC although also change other histone modifications (H3K9me3, H3K27me3) and through the GPR109A receptor. Conclusion Our initial results showed that patients with advanced CKD have low levels of SCFAs, and those were correlated with the renal function. Treatment of human renal and immune cells with propionate and butyrate induces profound changes in the chromatin structure, changing the whole-genome gene expression and modulating key pathways in the renal pathology. Increasing the SCFAs levels in those patients could be a potential therapeutic strategy to slow down the disease progression.

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

2019 ◽  
Vol 8 (8) ◽  
pp. 1090 ◽  
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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