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Abstract: SA-PO965

The Gut Microbiome Regulates Glomerular Filtration Rate

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Xu, Jiaojiao, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Gupta, Kunal, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Sanchez, Jason, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Gharaie, Sepideh, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Rabb, Hamid, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Pluznick, Jennifer L., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Background

Gut microbes influence physiology and pathophysiology. We hypothesized that gut microbes alter glomerular filtration rate (GFR).

Methods

Gut microbes were depleted using antibiotics in drinking water (ABX: 1g/L ampicillin, 1g/L neomycin, 0.5 g/L vancomycin). C57BL/6J male and female mice (6-weeks-old) were treated with ABX for 5 weeks, and GFR was measured by transcutaneous detection of FITC-sinistrin. Another cohort of mice were randomly assigned to four different groups (n=8 /sex/group): control diet (CD), high fat diet (HFD), CD + ABX, HFD + ABX. After 9 weeks, we analyzed body weight (BW), non-fasting glucose, insulin, GFR, glucose tolerance test (GTT), and insulin tolerance test (ITT).

Results

Bacteria reduction with ABX treatment was confirmed by qPCR of fecal samples using pan-bacterial primers (Ct for Females, F: Ctrl 13±0.2 vs ABX 21±0.4; Males, M: 13±0.1 vs ABX 20±0.4, n=8). GFR increased with ABX (F: 172±11 vs ABX 229±8, p=0.03; M: 167±7 vs ABX 266±15 μl/min, p=0.02, n=8). Next, we measured GFR in germ-free (GF) mice (born and raised without gut microbes), conventional mice (Ctrl, born with gut microbes), and conventionalized GF mice (CGF, born without gut microbes but given oral gavage of a fecal slurry with gut microbes). GFR increased in GF mice (F: 286±23, p<0.001; M: 248±17, p=0.002) versus both conventional (F: 163±6; M: 186±5) and CGF (F: 185±21, p=0.003; M: 186±7, p=0.002, n=7-8).
GFR also increases in high-fat diet (HFD) induced diabetic renal disease. To elucidate if mechanisms are similar, we measured GFR in mice on CD and HFD and/or with ABX. GFR was increased by HFD in both sexes. GFR in females was increased by ABX on CD (F: 182±13 vs. F+ ABX: 282±13; p=0.0005) and HFD (F: 290±20 vs. F+ ABX: 373±20; p=0.01). GFR in males increased with ABX on CD (M: 191±10 vs. M+ ABX: 263±10; p=0.04) but not HFD (M: 385±20 vs. M+ ABX: 390±33; NS). In both sexes, BW, GTT, and fasting glucose were affected by diet but not ABX. In females, ITT was affected by diet but not ABX. For males on a CD (but not HFD), ABX improved insulin responsiveness.

Conclusion

The absence (GF) and suppression (ABX) of gut microbes increase GFR. In females, the increased GFR from ABX and HFD are additive. The mechanisms of this microbe-GFR interaction merit further study.

Funding

  • NIDDK Support