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Associations of Inosine with Gut Microbiota, Metabolic Indicators, and Fluid Homeostasis in Kidney-Related Diarrhea
Huiyi Peng1,2, Qin Liu1,2, Zhoujin Tan1,2
1School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
Abstract:
As a natural purine metabolite, inosine's impact on kidney-related diarrhea through its influence on gut microbiota and associated metabolic functions remains unclear. Kidney-related diarrhea was induced in male KM mice. Histopathological alterations and inflammatory infiltration were assessed using hematoxylin and eosin (HE) staining. ELISA was used to measure corticosterone (CORT), antidiuretic hormone (ADH), and adenosine triphosphate (ATP) to assess metabolic status and fluid homeostasis. Immunohistochemistry (IHC) staining techniques, Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), and Western blot (WB) were used to analyze the expression of aquaporin-4 (AQP4), AMP-activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and adenosine A2A Receptor (A2AR). Gut microbiota composition and predicted functional pathways were analyzed using 16S rRNA sequencing and KEGG-based functional prediction, followed by correlation analyses between the microbiota and factors. Inosine improved renal function, alleviated renal and colonic histopathological damage, and reduced inflammatory infiltration. It also increased ATP, ADH, and CORT levels, indicating improvements in metabolic and fluid-balance-related factors. Inosine also increased A2AR, AMPK, and AQP4 expression while decreasing NF-κB expression. Moreover, inosine altered gut microbial composition and was associated with differences in predicted microbial functional pathways. Significant correlations were observed between specific bacterial taxa and host indicators. Inosine alleviated kidney-related diarrhea in mice, accompanied by improvements in metabolic status and fluid homeostasis, reduced inflammation, modulation of A2AR/AMPK/NF-κB-related signaling pathway, and alterations in gut microbial composition. Further studies are required to clarify the causal contributions of gut microbial composition and functional activity to the beneficial effects of inosine.
Insights
Inosine treatment improved kidney function and alleviated diarrhea in mice by reducing inflammation and altering gut bacteria. This purine metabolite also positively impacted metabolic status and fluid balance.
Area of Science:
- Biochemistry
- Microbiology
- Nephrology
Background:
- Kidney-related diarrhea pathogenesis is complex and linked to gut microbiota and metabolic dysregulation.
- The role of inosine, a natural purine metabolite, in this condition is not well understood.
- Investigating inosine's effects could reveal novel therapeutic strategies.
Purpose of the Study:
- To investigate the effects of inosine on kidney-related diarrhea in a mouse model.
- To explore inosine's impact on gut microbiota, metabolic status, and related signaling pathways.
- To determine the potential of inosine as a therapeutic agent for kidney-related diarrhea.
Main Methods:
- Induction of kidney-related diarrhea in male KM mice.
- Histopathological analysis (HE staining) for tissue damage and inflammation.
- ELISA for corticosterone (CORT), antidiuretic hormone (ADH), and adenosine triphosphate (ATP).
- Immunohistochemistry (IHC), RT-qPCR, and Western blot (WB) for protein and gene expression (AQP4, AMPK, NF-κB, A2AR).
- 16S rRNA sequencing for gut microbiota analysis and KEGG functional prediction.
- Correlation analysis between microbiota and host factors.
Main Results:
- Inosine treatment improved renal function and alleviated renal and colonic histopathological damage.
- Inosine increased levels of ATP, ADH, and CORT, indicating enhanced metabolic status and fluid homeostasis.
- Inosine modulated the A2AR/AMPK/NF-κB signaling pathway by upregulating A2AR, AMPK, and AQP4, and downregulating NF-κB.
- Inosine altered gut microbial composition and predicted functional pathways, with significant correlations observed between specific bacteria and host indicators.
Conclusions:
- Inosine effectively alleviates kidney-related diarrhea in mice.
- The therapeutic effects are associated with improved metabolic status, fluid homeostasis, reduced inflammation, and modulation of the A2AR/AMPK/NF-κB pathway.
- Inosine's impact on gut microbiota composition and function plays a role in its beneficial effects, warranting further investigation.
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