GUT MICROBOTA OF HEMODIALYSIS PATIENTS PRODUCCES HIGH LEVELS OF TRIMETHYLAMINE N-OXIDE, A RISK FACTERS FOR CARDIOVASCULAR COMPLICATIONS

 

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GUT MICROBOTA OF HEMODIALYSIS PATIENTS PRODUCCES HIGH LEVELS OF TRIMETHYLAMINE N-OXIDE, A RISK FACTERS FOR CARDIOVASCULAR COMPLICATIONS

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Hanae
Wakabayashi
Hanae Wakabayashi hawakaba@chiba-u.jp Chiba University Hospital Nephrology Chiba Japan *
Masayoshi Ishii m.ishii@chiba-u.jp Chiba University Hospital Nephrology Chiba Japan -
Hiroko Inoue h_inoue@chiba-u.jp Chiba University Hospital Nephrology Chiba Japan -
Takayuki Fujii f-taka@sis.seirei.or.jp Seirei Sakura Citizen Hospital Nephrology Sakura Japan -
Sumihiko Sato ssato@3109jp.com Ijyouhoujinsyadan credo Satou Clinic Dialysis Chiba Japan -
Masashi Aizawa mszw313@gmail.com Kimitsu Chuo Hospital Nephrology Kisarazu Japan -
Katsuhiko Asanuma kasanuma@chiba-u.jp Chiba University Hospital Nephrology Chiba Japan -
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The gut microbiota in patients with chronic kidney disease is characterized by dysbiosis. Since gut dysbiosis can affect kidney function and lead to various diseases, it is important to elucidate the characteristics of gut microbiota in patients with chronic kidney disease. Trimethylamine N-oxide (TMAO), a uremic toxin produced by the gut microbiota, promotes arteriosclerosis and increases the risk of cardiovascular complications. We conducted this study to clarify whether the gut microbiota of hemodialysis patients changes from healthy individuals, resulting in increased TMAO production.

We collected feces from 71 hemodialysis patients and 31 healthy controls in Chiba Prefecture and performed meta-16sRNA analysis with the cooperation of the Meiji Lactic Acid Bacteria Research Institute(Meiji Co., Ltd.). We performed inter-group comparison analysis using LEfSe (Linear discriminant analysis effect size) and predictive genomic analysis using PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States). We compared the levels of TMAO in the blood, the amount of fecal bacterial DNA sequences encoding the enzymes (cutC, D) that produce trimethylamine (TMA), a precursor of TMAO, between hemodialysis patients and healthy controls. To identify bacteria containing the cutC and D gene sequences, we performed a homology search using blastp.

We identified a significant difference in beta-diversity between the hemodialysis patient group and the healthy control group. The hemodialysis group showed an increased number of bacterial species compared to the control group, particularly an increase in rare bacterial species with a prevalence of less than 1%. This increase in rare bacterial species was associated with a relative decrease in Bifidobacteria, a major component of the gut microbiota in Japanese individuals. In the hemodialysis group, the blood TMAO concentration was significantly higher than in the control group. When the patients were grouped based on their years of dialysis treatment (in 5-year intervals), those with a longer dialysis history had higher TMAO concentrations. Furthermore, the number of reads for the cutC and D genes in fecal samples from the hemodialysis group was significantly increased, and the proportion of Clostridium bacteria carrying the cutC and D genes was also higher compared to the control group. 

The gut microbiota of hemodialysis patients deviates from the normal state. Increased abundance of multiple minority bacteria increases TMAO production, contributing to the risk of cardiovascular complications.

This research was presented at the 70th Annual Meeting of the Japanese Society for Dialysis Therapy.

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