| Objective: To sort out the literature sources of "treating the same disease with different methods" and its application in diarrhea treatment.According to the relationship between intestinal microbiota imbalance and diarrhea,the active components,targets and pathways of Gegen Qinlian Decoction and Huoxiang Zhengqi Powder were analyzed,and the characteristics of intestinal contents and intestinal mucosal microbiota imbalance of diarrhea with damp-heat syndrome and cold-dampness syndrome were compared to explore the biological basis of diarrhea with different syndromes.To analyze the difference between the two prescriptions in regulating the intestinal contents and intestinal mucosal microbiota imbalance in mice with diarrhea of traditional Chinese medicine(TCM)syndrome,and to explain the microecological mechanism of "treating the same disease with different methods".Finally,it provides a basis for "the same disease-different bacteria-different treatment".Methods:(1)Origin,connotation and specific content of " treating the same disease with different methods" were analyzed by literature tracing method.(2)The active components and targets of Gegen Qinlian Decoction and Huoxiang Zhengqi Powder were obtained from TCMSP database,and the targets of diarrhea were obtained from Genecard,OMIM and GEO databases,and then the prescription-disease target network was visualized and analyzed by Cytoscape.Protein interaction network was constructed by using STRING,and the function enrichment analysis of intersection targets was carried out.The binding activity of core effective components and core targets was preliminarily verified by molecular docking with Autodock.Finally,GSEA analysis was carried out based on GEO data set to further verify the related pathways.(3)Based on the high-throughput sequencing data of 16 S r RNA gene of diarrhea with damp-heat syndrome and cold-dampness syndrome,which were constructed by the tutor team in the early stage,the microbiota imbalance characteristics of intestinal contents and intestinal mucosa with different TCM syndromes were analyzed by using data mining methods such as difference analysis and random forest.(4)Based on the high-throughput sequencing data of 16 S r RNA gene of mice with Gegen Qinlian Decoction and Huoxiang Zhengqi Powder,which were constructed by the tutor team in the early stage,the characteristics of intestinal microbiota were analyzed by using data mining methods such as difference analysis and random forest.(5)Using co-occurrence network and function prediction to compare the interaction and functional differences of microbiota,and to explore the microbiota functional characteristics of diarrhea with damp-heat syndrome and cold-dampness syndrome.Results:(1)"Treating the same disease with different methods" originated from Huangdi Neijing in the Warring States Period,matured in Treatise on Exogenous Febrile Diseases in Han Dynasty,and has been passed down and developed by later physicians,and now it has become an important part of the theoretical system of TCM."Treating the same disease with different methods " means "same disease-different syndrome-different treatment",which embodies the longitudinal grasp of the commonness of diseases and the horizontal understanding of the essence of pathogenesis in TCM." Same disease-different bacteria-different treatment" enriches the content of "treating the same disease with different methods ".(2)The common components of Gegen Qinlian Decoction and Huoxiang Zhengqi Powder in treating diarrhea are mainly quercetin,apigenin and kaempferol,and their actions involve AKT1,TNF,TP53,Cancer pathway and MAPK signaling pathway.Puerarin,wogonin and tetrandrine are the main active components of Gegen Qinlian Decoction in treating diarrhea,which mainly regulate FN1,SMAD3,IL2 RA and PI3K-Akt signaling pathway and Th17 cell differentiation.The main effective components of Huoxiang Zhengqi Powder in the treatment of diarrhea are oleic acid,linolenic acid and nobiletin,and the related target pathways mainly involve ALB,CREB1,HNF4 A,PPAR signaling pathway and AMPK signaling pathway.(3)The F/B ratio of intestinal mucosa in diarrhea with damp-heat syndrome and cold-dampness syndrome is higher than that of intestinal contents,and the B/E ratio is less than 1.Although the intestinal contents and intestinal mucosa are similar in species richness and diversity,there are differences in microbiota composition.The characteristic microbiota of intestinal contents enrichment in diarrhea with damp-heat syndrome were Lactobacillus murinus,and the characteristic microbiota of intestinal mucosa enrichment were Rothia mucilaginosa and Porphyromonas pasteri.The characteristic microbiota of diarrhea with cold-dampness syndrome were Lactobacillus johnsonii and Lactobacillus reuteri,and the characteristic microbiota of intestinal mucosa enrichment were Candidatus Arthromitus sp.SFB mouse NYU and Enterobacter cloacae.The differential contribution rate of dominant bacteria in intestinal mucosa is greater than that in intestinal contents.(4)After Gegen Qinlian Decoction treatment,the characteristic microbiota of intestinal contents enrichment was Muribaculum intestinale and Akkermansia muciniphila,while the characteristic microbiota of intestinal mucosa enrichment was Streptococcus oralis and Lactobacillus crispatus.After Huoxiang Zhengqi Powder treatment,the characteristic microbiota of intestinal contents enrichment was Lactobacillus reuteri and Clostridium sp.ND2,and the characteristic microbiota of intestinal mucosa enrichment was Bacillus horikoshii and Pseudomonas veronii.(5)The complexity of the co-occurrence network of microbiota in different intestinal niches was different for diarrhea with damp-heat syndrome and cold-dampness syndrome.The corresponding intervention of Gegen Qinlian Decoction and Huoxiang Zhengqi Powder has increased the microbiota diversity and made the interaction between the microbiota closer.The core microbiota of the co-occurrence network has significant correlation with the different microbiota functions.Conclusions:(1)Theory of " treating the same disease with different methods" has a long history,and the proposal of "same disease-different bacteria-different treatment" greatly enriches the connotation of "treating the same disease with different methods" in TCM;(2)Gegen Qinlian Decoction and Huoxiang Zhengqi Powder have common and advantageous active components,targets and pathways in diarrhea with different treatments for the same disease;(3)There are differences in intestinal microbiota imbalance of diarrhea with different TCM syndromes,that is,"same disease-different syndrome-different bacteria",and "same disease syndrome" also has characteristic microbiota imbalance in different intestinal niches;(4)There are also differences in the efficacy of prescriptions in regulating diarrhea-related intestinal microbiota imbalance in different TCM syndromes,that is,"same disease-different syndrome-different bacteria-different treatment";(5)Microbiota imbalance related to energy metabolism is the characteristic of intestinal contents in diarrhea with damp-heat syndrome,while the imbalance of pro-inflammatory bacteria and anti-inflammatory bacteria is the characteristic of intestinal mucosa.The imbalance of intestinal contents and intestinal mucosal microbiota in diarrhea with cold-dampness syndrome was characterized by the enrichment of immune inflammatory regulators.Gegen Qinlian Decoction regulates the abundance of short-chain fatty acid bacteria in intestinal contents.In intestinal mucosa,it may treat diarrhea with damp-heat syndrome by regulating immune-microbial interaction.Huoxiang Zhengqi Powder regulates the abundance of butyric acid-producing bacteria in intestinal contents and intestinal mucosa of diarrhea with cold-dampness syndrome.(6)The characteristic microbiota of intestinal contents may have indirect effects through metabolites,while the characteristic microbiota of intestinal mucosa may interact with the host more directly.The high diversity of intestinal mucosal microbiota indicates that it is more likely to be an effective target for regulating diarrhea of different TCM syndromes. |
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