Low Protein Diet, Gut Microbiome and Chronic Kidney Disease

Exploring the Role of Low Protein Diet on the Gut Microbiome, Related Metabolites and Renal Function in Chronic Kidney Disease

Chronic kidney disease (CKD) is a worldwide public health dilemma because of close association with multiple comorbidities, demanding high cardiovascular events, mortality and expensive medical cost. Novel and effective therapeutic measures remain urgently needed to reduce burden and impact of disease. Advanced renal failure can profoundly alter the biochemical milieu of the gastrointestinal tract leading to a leak gut. Application of 16s rRNA gene analysis identified an increase of Clostridia, Actinobacteria, and Gammaproteobacteria in hemodialysis patients and decrease of Bifidobacterium and lactobacillus in peritoneal patients. This altered microbiome consequently affect production of indole or phenol derived uremic toxins leading to renal damage. Our preliminary results indicated reduced number and diversity of intestinal microbes CKD patients compared to normal. Different dietary nutrients can affect the gut microbiome and derive several deleterious metabolites leading to metabolic disarrangement. Clinically, low-protein diet should be prescribe to renal patients to preserve renal function and high fat content are usually recommended to avoid caloric malnutrition to dietary restriction. The changes of diet-microbiome-metabolite interaction are large unknown with this dietary manipulation. The aims of this study is to determine the renal progression-associated gene and taxonomic alterations bymetagenome-wide association studies and the functional characterization of gut microbiome in CKD patients receiving different low-protein or high-fat diets. The results of the study will provide insight on the exact role of dietary manipulation in CKD patients from gut-renal cross talk.

Inclusion Criteria: . Patients aged 30-90 years with diagnosis of CKD (defined as abovementioned). . Sign the inform consent and agree to participate in this study. . Compliant to low protein diet (defined as protein intake <0.8 g/Kg/day) for 4 weeks assessed by 24h urine urea estimates, before enrollment Exclusion Criteria: . History of any malignancy, liver cirrhosis, intestinal operation, irritable bowel syndrome, cardiovascular disease (defined as myocardial infarction, documented Q wave on EKG, unstable angina, coronary artery disease with stenosis > 75%, congestive heart failure with Ejection Fraction < 50% and cerebrovascular disease) in the past 3 months. . History of or infection disease requiring admission in the past 3 months or, concomitant antibiotics use. . Concomitant use of probiotics or prebiotics. . Pregnancy. . Renal transplant recipients.

Wu IW, Lee CC, Hsu HJ, Sun CY, Chen YC, Yang KJ, Yang CW, Chung WH, Lai HC, Chang LC, Su SC. Compositional and Functional Adaptations of Intestinal Microbiota and Related Metabolites in CKD Patients Receiving Dietary Protein Restriction. Nutrients. 2020 Sep 12;12(9):2799. doi: 10.3390/nu12092799.