Background: This study investigated the correlation among kidney function, intestinal enzyme activities, and microbial activity of adenine and Folium sennae -induced diarrhea model in mice, which provided a basis for clinical treatment of kidney-intestinal correlation. Methods: We performed different doses of adenine combined with Folium sennae intragastric administration to establish the animal model of diarrhea. We assessed thymus and spleen indexes, serum creatinine, urea nitrogen and uric acid contents, intestinal contents and mucosal enzyme activities, and microbial activity. Results: After modeling, mice presented increased serum creatinine and decreased urea nitrogen. Uric acid showed different changes in the different model groups. The thymus index in the model mice was trending downward, whereas the spleen index was the opposite. Moreover, model mice induced a non-significant increase in xylanase activity of the intestinal contents and mucosa compared to the control performance. Sucrase content of the intestinal contents increased considerably in the model groups but decreased in the intestinal mucosa. Lactase and amylase induced different trends in the different modeling methods. As well, the microbial activity of intestinal contents increased significantly, while that of intestinal mucosa decreased. Conclusion: Adenine combined with Folium sennae successfully replicated diarrhea in mice models. Using 50 mg/ (kg/day) adenine for 14 days in combination with 10 g/(kg/day) Folium sennae decoction for 7 days caused kidney function injury in diarrhea mice. In addition, kidney function injury was accompanied by changing in intestinal functional enzyme activity and microbial activity.

The present study aims to study and analyze the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Ten male mice were randomly divided into the control group and the model group. Diarrhea mice model with deficiency kidney-yang syndrome was established by adenine combined with Folium sennae. The kidney structure was observed by hematoxylin-eosin (HE) staining. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA). The characteristics of gut mucosal microbiota were analyzed by performing third-generation high-throughput sequencing. The results showed that the model mice exhibit obvious structural damage to the kidney. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels showed a decreased trend in the model group. The diversity and community structure of the gut mucosal microbiota improved in the model group. Dominant bacteria like Candidatus Arthromitus, Muribaculum, and Lactobacillus reuteri varied significantly at different taxonomic levels. The characteristic bacteria like Bacteroides, Erysipelatoclostridium, Anaerotignum, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii were enriched in the model group. A correlation analysis described that Erysipelatoclostridium was positively correlated with Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels, while Anaerotignum exhibited an opposite trend. Together, adenine combined with Folium sennae damaged the structure of the kidney, affected energy metabolism, and caused disorders of gut mucosal microbiota in mice. Bacteroides, Erysipelatoclostridium, and Anaerotignum showed significant inhibition or promotion effects on energy metabolism. Besides, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii might be the characteristic species of gut mucosal microbiota responsible for causing diarrhea with deficiency kidney-yang syndrome.

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