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Dysfunction of cecal microbiota and CutC activity in mice mediating diarrhea with kidney-yang deficiency syndrome
Mingmin Guo1, Leyao Fang2, Meili Chen3
1School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.
Objective:
Previous studies have indicated that diarrhea with kidney-yang deficiency syndrome leads to a disorder of small intestine contents and mucosal microbiota. However, the relationship of TMA-lyase (CutC) activity and TMAO with diarrhea with kidney-yang deficiency syndrome remains unexplored. Therefore, this study explores the relationship between cecal microbiota and choline TMA-lyase (CutC) activity, as well as the correlation between trimethylamine oxide (TMAO), inflammatory index, and CutC activity.
Method:
Twenty SPF-grade male KM mice were randomly divided into the normal group (CN) and the diarrhea model group (CD). Diarrhea mouse models were established by adenine combined with Folium sennae administration. CutC activity, TMAO, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were detected, and the cecal content microbiota was sequenced.
Result:
After 14 days, diarrhea occurred in the CD group. Compared with the CN group, there was no significant change in the activity of CutC in the small intestine of the CD group, while the activity of CutC in the cecum was significantly increased, and the levels of TMAO, IL-6, and TNF-α showed a significant increase. The Chao1 index, Observed_species index, Shannon index, and Simpson index all exhibited a decreasing trend. The main changes at the bacterial genus level were Alistipes, Enterorhabdus, Desulfovibrio, Bacteroides, Candidatus_Saccharimonas, and [Ruminococcus]_torques_group. The results of LEfSe analysis, random forest analysis and ROC curve analysis revealed Paludicola, Blautia, Negativibacillus, Paraprevotella, Harryflintia, Candidatus_Soleaferrea, Anaerotruncus, Oscillibacter, Colidextribacter, [Ruminococcus]_torques_group, and Bacteroides as characteristic bacteria in the CD group. Correlation analysis showed a significant negative correlation between cecal CutC activity and Ligilactobacillus, and a significant positive correlation with Negativibacillus and Paludicola. The level of TMAO was significantly positively correlated with CutC activity and IL-6.
Conclusion:
Diarrhea with kidney-yang deficiency syndrome significantly affects the physiological status, digestive enzyme activity, CutC activity, TMAO levels, and inflammatory response in mice. Additionally, there are changes in the composition and function of cecal microbiota, indicating an important impact of diarrhea with kidney-yang deficiency syndrome on the host intestinal microbiota balance. The occurrence of diarrhea with kidney-yang deficiency syndrome may be associated with dysbiosis of intestinal microbiota, increased CutC activity, elevated TMAO levels, and heightened inflammatory factor levels.
Insights
Diarrhea with kidney-yang deficiency syndrome increases cecal trimethylamine N-oxide (TMAO)-lyase (CutC) activity and trimethylamine N-oxide (TMAO) levels, altering gut microbiota. This suggests a link between dysbiosis, elevated TMAO, and inflammation in this condition.
Area of Science:
- Microbiology
- Gastroenterology
- Metabolomics
Background:
- Diarrhea associated with kidney-yang deficiency syndrome is linked to small intestine dysbiosis.
- The specific roles of trimethylamine N-oxide (TMAO)-lyase (CutC) activity and TMAO in this condition are not well understood.
Purpose of the Study:
- To investigate the relationship between cecal microbiota and CutC activity in a mouse model of diarrhea with kidney-yang deficiency syndrome.
- To explore the correlation between TMAO, inflammatory markers, and CutC activity.
Main Methods:
- Diarrhea models were established in mice using adenine and Folium sennae.
- Cecal microbiota composition was analyzed via sequencing.
- CutC activity, TMAO, IL-6, and TNF-α levels were measured.
Main Results:
- Cecal CutC activity, TMAO, IL-6, and TNF-α levels were significantly increased in the diarrhea group compared to controls.
- Microbiota analysis revealed significant alterations in bacterial genera, including a decrease in diversity indices.
- CutC activity showed correlations with specific bacteria (e.g., Negativibacillus, Paludicola) and TMAO levels correlated positively with inflammation.
Conclusions:
- Diarrhea with kidney-yang deficiency syndrome significantly impacts cecal microbiota, CutC activity, TMAO levels, and inflammatory responses.
- Intestinal dysbiosis, increased CutC activity, elevated TMAO, and heightened inflammation are associated with this condition.
