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Abstract: FR-OR129

Dysbiosis in Renal Failure Causes Insulin Resistance and Leaky Gut

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1301 Health Maintenance, Nutrition, and Metabolism: Basic


  • Uchiyama, Kiyotaka, Keio University, School of Medicine, Tokyo, Japan
  • Wakino, Shu, Keio University, School of Medicine, Tokyo, Japan
  • Ito, Tomoaki, Keio University, School of Medicine, Tokyo, Japan
  • Tajima, Takaya, Keio University, School of Medicine, Tokyo, Japan
  • Matsui, Ayumi, Keio University, School of Medicine, Tokyo, Japan
  • Itoh, Hiroshi, Keio University, School of Medicine, Tokyo, Japan

Chronic Kidney disease (CKD) leads to clinically relevant insulin resistance (IR), which is a novel cardiovascular risk factor in patients with CKD. However, the pathophysiology of IR in CKD remains unclear. Recently, gut microbiota alterations have been reported to be associated with the etiology and progression of CKD. Using germ-free mice, we sought to determine whether dysbiosis in renal failure (RF) contributes to CKD-associated IR.


RF was induced in 7-week-old male ICR mice by feeding a diet containing 0.2% adenine for 6 weeks; these were compared with a control group that was fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage on the 8-week-old, germ-free, male, ICR mice using cecal microbiota obtained from either the control group (control-FMT) or RF group (RF-FMT). The vehicle group was gavaged with only sterile phosphate-buffered saline. Two weeks after inoculation, glucose and insulin tolerance and intestinal microbiota and barrier function were evaluated in each group.


In the mice from the RF group, whose body and adipose tissue weight were markedly lower, IR was evident where insulin stimulation failed to activate insulin signaling in skeletal muscles and adipose tissues. The expression of tight junctions in the colon was also reduced. In the RF-FMT group, glucose and insulin tolerance were impaired compared with those in the control-FMT and vehicle groups; insulin-induced signal transduction was attenuated, especially in skeletal muscles. Additionally, adipose tissue weight, adipocyte size and tight junction protein expression in the colon were lower in the RF-FMT group compared with those in the control-FMT group. These results mimicked those of the RF and the control groups. The differences in gut microbiota between the RF and control groups were mostly consistent between the RF-FMT and the control-FMT groups, including a decrease in Bacteroides and Prevotella species and an increase in Clostridium species in the RF and RF-FMT groups.


The gut microbiota from mice with RF induced IR along with impaired adipose tissue maturation, and disruption of the intestinal barrier associated with RF. Our data demonstrated for the first time, that uremic dysbiosis directly affects CKD-related metabolic abnormality.