关键词: 慢性肾脏病, 肠道微生物, 肠源性尿毒素, 硫酸对甲酚

Abstract:  Objective:To investigate the effects of R.gnavus on chronic kidney disease（CKD） and the clearance of p-cresol sulfate（pCS）.    Methodology:Fecal samples were collected from 40 peritoneal dialysis（PD） patients and subjected to 16S ribosomal RNA（16S rRNA） sequencing.  Patients  were  divided into  two  groups  based on median serum pCS.  Linear discriminant analysis effect size （LEfSe） and co-occurrence network analysis identified R. gnavus as a key genus in patients with low serum  pCS  levels.  20  C57BL/6  mice  were  randomly  divided  into  four  groups:  normal  control（CN） group，  CKD group， R. gnavus+CKD group and CN feces+CKD group. A pseudo-sterile CKD mice model was induced by the combination of quadruple antibiotics and an adenine diet. qRT-PCR was used to assess the relative abundance of R. gnavus in feces， the expression of  renal  transporters  and  inflammatory  factors;  ELISA  was  used  to  detect  serum  urea  nitrogen  and  creatinine. Kidney pathology  was  assessed  by  HE  and  Masson  staining;  serum  pCS  concentrations  were  measured  using  ultra-high performance liquid chromatography-tandem  mass  spectrometry（UPLC-MS/MS）.     Results: In  PD  patients，  R.  gnavus  was negatively correlated with serum pCS levels， and R. gnavus was a key genus in the intestinal flora of PD patients with low pCS levels. In the adenine-induced CKD model， administration of R. gnavus significantly improved renal function（P<0.05）， and attenuated renal fibrosis（P<0.05）; the mRNA expression of inflammatory factors in the kidney and colon was reduced（P< 0.05）. Furthermore， the  expression  of  renal  transporter  protein  organic  anion  transporter  3 （OAT3）， multidrug  resistance protein 4  （MRP4）， ATP  binding  cassette  subfamily  G  member  2  （ABCG2） was  significantly  up-regulated，  and  the concentration of  serum  pCS  was  markedly  reduced  following  R.  gnavus  treatment （P < 0.05）.     Conclusion: Enhanced intestinal colonization by R. gnavus promotes pCS clearance and mitigate CKD progression.

Key words:  chronic kidney disease, gut microbiota , gut-derived uremic toxin, p-cresol sulfate