| Authors |
Xu J, Verma E, Sanchez J, Gharaie S, Jeong S, Patel SK, Gooya M, Rosa X, Gupta
K, Rinschen MM, Rabb H, Pluznick JL
|
| Submitted By |
Submitted Externally on 8/18/2026 |
| Status |
Published |
| Journal |
Journal of the American Society of Nephrology : JASN |
| Year |
2026 |
| Date Published |
1/1/2026 |
| Volume : Pages |
37 : 36 - 48 |
| PubMed Reference |
40728891 |
| Abstract |
Microbes regulate GFR in health and CKD in mice. Tubuloglomerular feedback
initially contributes to the microbial modulation of GFR., Microbes are
implicated in a variety of host physiologic and pathophysiologic processes. In
this study, we tested the hypothesis that microbes modulate GFR in health and
CKD., To uncover the effect of gut microbiota on kidney function in health and
in a CKD model, we examined GFR, plasma creatinine, and kidney histology in mice
when gut microbes were manipulated., In healthy mice, GFR was significantly
increased when gut microbiota were either suppressed (oral antibiotics) or
absent (germ-free). In mice challenged with adenine diet to induce CKD with
impaired GFR, suppressing gut microbes with oral antibiotics also increased GFR.
In females on an adenine diet, oral antibiotics increased GFR versus adenine
alone on weeks 4 and 6. In males, oral antibiotics elevated GFR on week 2.
Adenine diet significantly increased plasma creatinine and kidney fibrosis; this
was suppressed by oral antibiotics in both sexes. To explore the mechanism, we
tested the hypothesis that altered tubuloglomerular feedback contributes to
elevated GFR using the sodium-glucose cotransporter 2 inhibitor empagliflozin;
empagliflozin impairs Na+ reabsorption in the proximal tubule, altering
tubuloglomerular feedback. Empagliflozin impaired antibiotics-induced GFR
increases on week 3 but not week 5, suggesting that altered tubuloglomerular
feedback contributes to the initial increase in GFR., The microbiome plays a key
role in “setting” baseline GFR by a mechanism that partially involves
tubuloglomerular feedback, and suppressing gut microbes can elevate GFR even in
CKD mice.
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