POS-239 MULTI-OMICS INTEGRATION REVEALS SIGNATURE OF GUT MICROBIAL METAGENOME AND FUNCTIONALITY IN RENAL PATIENTS RECEIVING PROTEIN RESTRICTION: A PROSPECTIVE RANDOMIZED STUDY

Abstract

Introduction: Knowledge on diet‐microbiome‐metabolite interaction of Chronic Kidney Disease (CKD) patients remains mandatory to support long‐term dietary interventions. However, comprehensive discernment of relationship between change of gut microbiota and multi‐omics profiling associated with dietary low protein restriction has been unraveled incompletely in CKD patients using cutting‐edge technology. Methods: This prospective study evaluated the association of change of gut microbiota at species level (determined using shotgun sequencing of fecal samples), target metabolomics and immune chemokines with renal progression in 47 patients receiving different daily protein intake. The CKD patients were randomized to receive a daily protein intake of < 0.8g/kg body weight/day, for 3 months (17 control, 15 CKD‐low protein, 15 CKD‐normal protein). Results: The mean age of participants was 64.1 ± 6 years and 21 (44.7%) were men. Mean estimated glomerular filtration rate (eGFR) was 119.2 vs. 33.1 mL/min/1.73m2in the control and CKD patients, respectively. The changes of eGFR were ‐1.8 vs. ‐4.6 mL/min/1.73m2in the CKD‐low protein vs. CKD‐normal protein patients (p= 0.014). We identify significant differences on the relative abundance of 22 microbial species (Actinomyces oral‐448, Porphyromonas gingivalis, Niameybacter massiliensis, Streptococcus gordonii, Faecalibacterium prausnitzii, Clostridium sp. SY8519, Anaeromassilibacillus marseille‐P3371, Bifidobacterium bifidum, Lactobacillus sanfranciscensis, Dorea longicatena, Lactobacillus mucosae, Clostridiales bacterium‐VE202‐21, Butyricimonas sp.An62, Bifidobacterium animalis, Streptococcus mutans, Lactobacillus fermentum, Coprococcus eutactus, Alistipes shahii, Lactococcus garvieae, Roseburia inulinivorans, Prevotella copri andBifidobacterium pseudocatenulatum) and serum concentration of 5 metabolites (glyco‐muricholic acid, nonanoic acid, Isovaleric acid, hexanoic acid, octanoic acid) and 2 cytokines (RANTES and hepatocyte growth factor) between CKD‐low protein vs. CKD‐normal protein. Serum levels of indoxyl sulfate and p‐cresyl sulfate did not differ between the two groups. Microbial genes related to amino acids metabolism and lipopolysaccharide biosynthesis were differentially depleted, while pathway modules related to glutathione and D‐alanine metabolism were enriched in the CKD‐low protein patients. Our analyses reveal signatures and functions of gut microbiota to adapt dietary protein restriction in renal patients. Conclusions: Our multi‐omics data reveal the connections between gut metagenome and serum metabolite (or immune markers) in CKD patients receiving low protein diet. Changes in microbial metabolism and host inflammation may contribute to renal health in CKD patients under protein restriction. No conflict of interest