scholarly journals Chronic Kidney Disease, Gut Dysbiosis, and Constipation: A Burdensome Triplet

2020 ◽  
Vol 8 (12) ◽  
pp. 1862
Author(s):  
Ryota Ikee ◽  
Naomi Sasaki ◽  
Takuji Yasuda ◽  
Sawako Fukazawa
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Responses ◽  
Bacterial Species ◽  
Short Chain Fatty Acids ◽  
Uremic Toxins ◽  
Fermentation Products ◽  
Bacterial Fermentation ◽  
Gut Dysbiosis ◽  
Multiple Drugs

Gut dysbiosis has been implicated in the progression of chronic kidney disease (CKD). Alterations in the gut environment induced by uremic toxins, the dietary restriction of fiber-rich foods, and multiple drugs may be involved in CKD-related gut dysbiosis. CKD-related gut dysbiosis is considered to be characterized by the expansion of bacterial species producing precursors of harmful uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, and the contraction of species generating beneficial short-chain fatty acids, such as butyrate. Gut-derived uremic toxins cause oxidative stress and pro-inflammatory responses, whereas butyrate exerts anti-inflammatory effects and contributes to gut epithelial integrity. Gut dysbiosis is associated with the disruption of the gut epithelial barrier, which leads to the translocation of endotoxins. Research on CKD-related gut dysbiosis has mainly focused on chronic inflammation and consequent cardiovascular and renal damage. The pathogenic relationship between CKD-related gut dysbiosis and constipation has not yet been investigated in detail. Constipation is highly prevalent in CKD and affects the quality of life of these patients. Under the pathophysiological state of gut dysbiosis, altered bacterial fermentation products may play a prominent role in intestinal dysmotility. In this review, we outline the factors contributing to constipation, such as the gut microbiota and bacterial fermentation; introduce recent findings on the pathogenic link between CKD-related gut dysbiosis and constipation; and discuss potential interventions. This pathogenic link needs to be elucidated in more detail and may contribute to the development of novel treatment options not only for constipation, but also cardiovascular disease in CKD.

MO460ASSOCIATION BETWEEN CARBAMYLATED ALBUMIN, GUT MICROBIOTA AND THEIR DERIVED METABOLITES IN CHRONIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mieke Steenbeke ◽  
Sophie Valkenburg ◽  
Wim Van Biesen ◽  
Joris Delanghe ◽  
Marijn Speeckaert ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Plasma Levels ◽  
Pearson Correlation ◽  
Bacterial Species ◽  
Study Cohort ◽  
Gut Dysbiosis ◽  
Symmetry Factor ◽  
Cardiovascular Morbidity And Mortality

Abstract Background and Aims Chronic kidney disease (CKD) is characterized by gut dysbiosis. We recently demonstrated a decrease of short-chain fatty acid (SCFA) producing bacterial species with the progression of CKD. Besides, levels of protein-bound uremic toxins (PBUTs) and post-translational modifications of protein are increased in CKD, both are risk factors for accelerated cardiovascular morbidity and mortality. The link between the gut-kidney axis and protein carbamylation is unclear. The aim of the study was to explore the relation between carbamylated albumin, estimated by the albumin symmetry factor, and plasma levels of PBUTs, fecal levels of SCFAs (ongoing), and the abundance of related gut microbiota in different stages of CKD (1-5). Method The study cohort includes 103 non-dialyzed CKD patients (stages 1-5). Serum proteins were detected by capillary electrophoresis and UV absorbance at 214 nm with the symmetry factor as a marker of albumin carbamylation [the lower the symmetry factor, the more carbamylated albumin]. The quantification of PBUTs and SCFAs in plasma and fecal samples, respectively, using validated UPLC methods. Results The Pearson correlation coefficient (r) shows a positive correlation between the albumin symmetry factor and the estimated glomerular filtration rate (eGFR) (r=0.3025; p=0.0019). The albumin symmetry factor correlates positively with the abundance of Butyricicoccus spp. (r= 0.3211; p=0.0009), Faecalibacterium prausnitzii (r=0.2765; p=0.0047) and Roseburia spp. (r=0.2527; p=0.0100) and negatively with the PBUTs, p-cresyl sulfate (pCS) (r=-0.2819; p=0.0039), p-cresyl glucuronide (pCG) (r=-0.2819; p=0.0039) and indoxyl sulfate (IxS) (r=-0.2650; p=0.0068). Conclusion The decreased abundance of SCFA producing gut bacteria with the progression of CKD can evoke unfavorable conditions in the gut. This can contribute to increased plasma levels of PBUTs potentially (indirectly) playing a role in albumin carbamylation. It will be further explored whether fecal levels of SCFAs are affected in parallel and could be potential targets to restore gut dysbiosis and uremia.

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.

scholarly journals Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model

2018 ◽  
Vol 315 (4) ◽  
pp. F824-F833 ◽  
Author(s):  
Eikan Mishima ◽  
Shinji Fukuda ◽  
Yoshitomi Kanemitsu ◽  
Daisuke Saigusa ◽  
Chikahisa Mukawa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Kidney Disease ◽  
Therapeutic Option ◽  
Short Chain Fatty Acids ◽  
Inhibitory Effect ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Vehicle Group ◽  
Microbiota Composition

Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins, including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg po) treatment did not influence the impaired renal function; however, it significantly reduced the plasma levels of p-cresyl sulfate and indoxyl sulfate in renal failure mice (a 75% and 26% reduction, respectively, compared with the vehicle group). Additionally, canagliflozin significantly increased cecal short-chain fatty acids in the mice, suggesting the promotion of bacterial carbohydrate fermentation in the intestine. Analysis of the cecal microbiota showed that canagliflozin significantly altered microbiota composition in the renal failure mice. These results indicate that canagliflozin exerts intestinal effects that reduce the accumulation of uremic toxins including p-cresyl sulfate. Reduction of accumulated uremic toxins by canagliflozin could provide a potential therapeutic option in chronic kidney disease.

scholarly journals Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients

2020 ◽  
Vol 21 (6) ◽  
pp. 1986 ◽  
Author(s):  
Tessa Gryp ◽  
Geert R.B. Huys ◽  
Marie Joossens ◽  
Wim Van Biesen ◽  
Griet Glorieux ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Bacterial Species ◽  
Uremic Toxins ◽  
Bacterial Number ◽  
Uremic Toxin ◽  
Microbial Composition ◽  
Indolic Compounds ◽  
Cardiovascular Morbidity And Mortality

In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid, originate from phenolic and indolic compounds, which are end products of gut bacterial metabolization of aromatic amino acids (AAA). This study investigates gut microbial composition at different CKD stages by isolating, identifying and quantifying PBUT precursor-generating bacteria. Fecal DNA extracts from 14 controls and 138 CKD patients were used to quantify total bacterial number and 11 bacterial taxa with qPCR. Moreover, isolated bacteria from CKD 1 and CKD 5 fecal samples were cultured in broth medium supplemented with AAA under aerobic and anaerobic conditions, and classified as PBUT precursor-generators based on their generation capacity of phenolic and indolic compounds, measured with U(H)PLC. In total, 148 different fecal bacterial species were isolated, of which 92 were PBUT precursor-generators. These bacterial species can be a potential target for reducing PBUT plasma levels in CKD. qPCR indicated lower abundance of short chain fatty acid-generating bacteria, Bifidobacterium spp. and Streptococcus spp., and higher Enterobacteriaceae and E. coli with impaired kidney function, confirming an altered gut microbial composition in CKD.

scholarly journals Gut-Derived Protein-Bound Uremic Toxins

Toxins ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 590 ◽  
Author(s):  
Amanda L. Graboski ◽  
Matthew R. Redinbo
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Filtration Rate ◽  
Therapeutic Strategies ◽  
Uremic Toxins ◽  
Uremic Toxin ◽  
Risk Of Death ◽  
Gut Dysbiosis ◽  
Causes Of Mortality

Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration rate begins to fall, uremic toxins accumulate in the serum and significantly increase the risk of death from cardiovascular disease and other causes. Several of the most harmful uremic toxins are produced by the gut microbiota. Furthermore, many such toxins are protein-bound and are therefore recalcitrant to removal by dialysis. We review the derivation and pathological mechanisms of gut-derived, protein-bound uremic toxins (PBUTs). We further outline the emerging relationship between kidney disease and gut dysbiosis, including the bacterial taxa altered, the regulation of microbial uremic toxin-producing genes, and their downstream physiological and neurological consequences. Finally, we discuss gut-targeted therapeutic strategies employed to reduce PBUTs. We conclude that targeting the gut microbiota is a promising approach for the treatment of CKD by blocking the serum accumulation of PBUTs that cannot be eliminated by dialysis.

scholarly journals Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 809
Author(s):  
Mieke Steenbeke ◽  
Sophie Valkenburg ◽  
Tessa Gryp ◽  
Wim Van Biesen ◽  
Joris R. Delanghe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Intestinal Barrier ◽  
Uremic Toxins ◽  
Intestinal Barrier Function ◽  
Post Translational Modifications ◽  
Gut Dysbiosis ◽  
Cardiovascular Morbidity And Mortality

Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (n = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations (rs = 0.212; p = 032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of p-cresol correlate with its derived plasma UTs (p-cresyl sulfate: rs = 0.342, p < 0.001; p-cresyl glucuronide: rs = 0.268, p = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid (rs = 0.306; p = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR (rs = 0.274; p = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia in needed.

scholarly journals Constipation in chronic kidney disease: it is time to reconsider

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Ryota Ikee ◽  
Kazuhiro Yano ◽  
Tomomi Tsuru
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Intestinal Motility ◽  
Intestinal Inflammation ◽  
Colonic Transit ◽  
Uremic Toxins ◽  
Phosphate Binders ◽  
Limited Information ◽  
Gut Dysbiosis

AbstractConstipation is highly prevalent in patients with chronic kidney disease (CKD) and is primarily characterized by decreased intestinal motility. This chronic disorder affects the quality of life of patients. However, nephrologist and dialysis clinicians have long had a disproportionately limited understanding of constipation. Accumulating evidence has revealed a relationship between constipation and cardiovascular disease and CKD. The pathogenesis of constipation in CKD patients is multifactorial: decreased physical activity, comorbidities affecting bowel movement, such as diabetes mellitus, cerebrovascular disease, and hyperparathyroidism, a restricted dietary intake of plant-based fiber-rich foods, and multiple medications, including phosphate binders and potassium-binding resins, have all been implicated. CKD is associated with alterations in the composition and function of the gut microbiota, so-called gut dysbiosis. Recent studies showed that CKD-related gut dysbiosis decreased intestinal motility via intestinal inflammation or the increased generation of gut-derived uremic toxins, such as indoxyl sulfate and p-cresyl sulfate. Furthermore, the gastrointestinal secretion of mucin was found to be decreased in CKD animal models, which may delay colonic transit by diminished lubrication in the alimentary tract. Thus, CKD-related gut dysbiosis may play a role in constipation, but limited information is currently available. Since constipation is often intractable, particularly in CKD patients, every available means needs to be employed in its treatment. The effects of probiotics, prebiotics, and synbiotics on the composition of the gut microbiota and gut-derived uremic toxins have been increasingly reported. However, their effects on stool consistency or frequency in CKD patients remain unclear. Some laxatives may be beneficial for improving not only bowel habits but also gut dysbiosis. Further studies are required to elucidate the CKD-specific pathogenesis of constipation and develop novel effective treatment options.

scholarly journals Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

2018 ◽  
Vol 132 (5) ◽  
pp. 509-522 ◽  
Author(s):  
Wei Ling Lau ◽  
Javad Savoj ◽  
Michael B. Nakata ◽  
Nosratola D. Vaziri
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Intestinal Wall ◽  
Uremic Toxins ◽  
Blood Levels ◽  
Systemic Effects ◽  
Kidney Fibrosis ◽  
Microbial Dysbiosis

In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p-cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects. In this review, we discuss the evidence supporting a role for gut-derived uremic toxins in promoting multiorgan dysfunction via inflammatory, oxidative stress, and apoptosis pathways. End-organ effects include vascular calcification, kidney fibrosis, anemia, impaired immune system, adipocyte dysfunction with insulin resistance, and low turnover bone disease. Higher blood levels of gut-derived uremic toxins are associated with increased cardiovascular events and mortality in the CKD population. Clinical trials that have examined interventions to trap toxic products or reverse gut microbial dysbiosis via oral activated charcoal AST-120, prebiotics and probiotics have not shown impact on cardiovascular or survival outcomes but were limited by sample size and short trials. In summary, the gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD.

scholarly journals P0703IDENTIFICATION AND QUANTIFICATION OF UREMIC TOXIN PRECURSORS-GENERATING GUT BACTERIA IN CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tessa Gryp ◽  
Mario Vaneechoutte ◽  
Marie Joossens ◽  
Wim Van Biesen ◽  
Griet Glorieux
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Bacterial Species ◽  
Uremic Toxins ◽  
Anaerobic Conditions ◽  
Microbial Composition ◽  
Fecal Samples ◽  
Indolic Compounds ◽  
Ckd Stage

Abstract Background and Aims In chronic kidney disease (CKD), impaired kidney function results in the accumulation of uremic toxins, which exert deleterious biological effects, contributing to cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid (IAA), originate from phenolic and indolic compounds, which are end products of the gut bacterial metabolization of aromatic amino acids (AAA). This study investigated the microbial composition in different stages of CKD by isolating, identifying and quantifying PBUT precursor-generating bacteria from fecal samples. Method Using fecal samples from patients in CKD stage 1 (n=6) and stage 5 (n=6), bacteria were cultured in a yeast casitone fatty acid glucose broth medium supplemented with AAA under aerobic (2d at 37°C) and anaerobic conditions (7d at 37°C), and confirmed as PBUT precursor-generating bacteria based on their generation capacity of phenolic and indolic compounds, measured with (U)HPLC. Next, fecal DNA from 14 controls, 111 non-dialyzed and 27 dialyzed CKD patients was used to quantify the total bacterial number but also of 11 of the identified PBUT precursor-generating bacteria with qPCR. Using a Kruskal-Wallis test, bacterial loads were compared between the different CKD stages and control. Correlations between disease stages (control and CKD 1-5) and the abundance of bacterial species were assessed with the Spearman’s rank test. Results In total, 150 different bacterial species were isolated from the CKD fecal samples, of which 101 were identified and 92 classified as PBUT precursor-generating bacteria. In general, p-cresol and phenol were mainly generated under anaerobic conditions, while indole and IAA were generated under both aerobic and anaerobic conditions. Phenolic compounds and IAA were predominantly generated by bacterial species belonging to the Bacteroidaceae, Clostridiaceae, Enterococcaceae and Tannerellaceae, while indolic compounds were mainly generated by Bifidobacteriaceae and Enterobacteriaceae. Quantitative analysis of 11 confirmed PBUT precursor-generating bacteria revealed a higher abundance of Streptococcus spp. and Enterobacteriaceae in fecal samples from HD patients compared to controls and early CKD stages, and for Roseburia spp. compared to CKD 5. Moreover, in HD, the abundance of Clostridioides difficile and Lactobacillus spp. was increased compared to CKD 1-5, and of Escherichia coli compared to control (all p&gt;0.05). The abundance of Bacteroides spp., Faecalibacterium prausnitzii, Akkermansia muciniphila and Bifidobacterium spp. as well as the total number of bacteria was comparable among the different CKD stages and controls. Finally, decrease in kidney function (ranging from control to CKD 5) positively correlated with the abundance of Enterobacteriaceae (rs=0.210), and E. coli (rs=0.286), while an inverse correlation was found with Streptococcus spp. (rs=-0.255), Butyricoccus spp. (rs=-0.326), F. prausnitzii (rs=-0.250), Roseburia spp. (rs=-0.342) and Bifidobacterium spp. (rs=-0.303) (all p&gt;0.05). Conclusion The identified PBUT precursor-generating bacteria are potential targets to reduce the plasma PBUT levels in CKD. In addition, in this CKD cohort, based on qPCR, an altered gut microbial composition with the progression of CKD could be established/confirmed.

scholarly journals Short-Chain Fatty Acids: A Soldier Fighting Against Inflammation and Protecting From Tumorigenesis in People With Diabetes

2020 ◽  
Vol 11 ◽  
Author(s):  
Qiyu Yang ◽  
Jing Ouyang ◽  
Fengjun Sun ◽  
Jiadan Yang
Keyword(s):  
Fatty Acids ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Microbial Translocation ◽  
Short Chain ◽  
Fermentation Products ◽  
Gut Dysbiosis ◽  
Risk Of Cancer ◽  
Chain Fatty Acids

Converging evidences showed that people with diabetes mellitus (DM) have significantly higher risk for different cancers, of which the exact mechanism underlying the association has not been fully realized. Short-chain fatty acids (SCFAs), the fermentation products of the intestinal microbiota, are an essential source for energy supply in gut epithelial cells. They have been reported to improve intestinal barrier integrity, prevent microbial translocation, and further dampen inflammation. Gut dysbiosis and reduction in SCFA-producing bacteria as well as SCFAs production in the intestine are commonly seen in metabolic disorders including DM and obesity. Moreover, inflammation can contribute to tumor initiation and progression through multiple pathways, such as enhancing DNA damage, accumulating mutations in tumor suppressor genes Tp53, and activating nuclear factor-kappa B (NF-κB) signaling pathways. Based on these facts, we hypothesize that lower levels of microbial SCFAs resulted from gut dysbiosis in diabetic individuals, enhance microbial translocation, and increase the inflammatory responses, inducing tumorigenesis ulteriorly. To this end, we will discuss protective properties of microbial SCFAs and explore the pivotal roles SCFAs played in the link of DM with cancer, so as to take early precautions to reduce the risk of cancer in patients with DM.

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