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Kidney Week

Abstract: PO0615

Effects of Chronic Intermittent Hypoxia on umod-/- Rats' Model Link to Alterations of Gut Microbiota

Session Information

  • CKD Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Wang, Na, Renal division, Peking University First Hospital, Beijing, China
  • Chen, Yuqing, Renal division, Peking University First Hospital, Beijing, China
Background

Previous studies showed that both obstructive sleep apnea and uromodulin (UMOD) were associated with gut microbiota regulation. Here we explored the interaction effects of chronic intermittent hypoxia (CIH) and UOMD expression on variation of gut microbiota and association with phenotype.

Methods

umod-/- and wild type (WT) Sprague Dawley rats were attributed into 4 groups (N=10 in each group), umod-/- and WT under CIH, umod-/- and WT under normal air. All four groups were fed with same chaw for 10 weeks. All rats were anesthetized to collect fecal samples from large intestine directly and blood at the end of 10 weeks feeding. The bacterial composition was analyzed based on 16S ribosomal DNA pyrosequencing. Bioinformatics tools, including sequence alignment, abundance, and taxonomic diversity, were used in microbiome data analyses. Correlation analysis between differential genera and changed biochemical indicators were measured.

Results

Under normoxia, the serum phosphorus(P*) tend to be lower in umod-/- group compared with WT group (1.9±0.2 vs 2.1±0.2mmol/L, P=0.064). Under normoxia environment, the α-diversity of gut microbiota decreased in umod-/- group compared with WT group (Chao1 index, 301.8±30.2 vs 374.3±55.3,P=0.005), and the composition of microbiota was clearly separated between two groups (PCoA, P<0.001). The abundance of g-Lactobacillus (P=0.002) and g-Phascolarctobacterium (P=0.026) increased and g-Ruminococcus (P=0.023) decreased in umod-/- group compared with WT group. g-Ruminococcus showed positive relationship with serum phosphorus (R=0.511, P=0.043).
When CIH was added as an environment condition, the serum phosphorus(P*) increased in umod-/- group obviously (2.3±0.3 vs 1.8±0.2 mmol/L,P=0.002). Gut composition in umod-/- were still clearly separated from WT (PCoA, P<0.001). The abundance of g-Lactobacillus, g-Phascolarctobacterium and g-Ruminococcus showed no difference. The abundance of g-Blautia (P=0.008), g-Sutterella (P=0.008), g-Anaerostipes (P=0.008) increased and g-Flavonifractor (P=0.008) and g-Anaerotruncus (P=0.008) decreased in umod-/- CIH group compared with wild type CIH group. G-Sutterella showed positive relationship with Phosphorus (R=0.831, P<0.001).

Conclusion

Chronic intermittent hypoxia can interact with uromodulin to affect serum phosphorous in umod-/- rats. These changes were strongly linked to the alterations in gut microbiota.