Comprehensive microbiomes and fecal metabolomics combined with network pharmacology reveal the effects of Jichuanjian on aged functional constipation

Background: Functional constipation is a common gastrointestinal disorder especially severely affecting the life quality of the aged. Jichuanjian (JCJ) has been widely used for aged functional constipation (AFC) in clinic. Yet, the mechanisms of JCJ merely scratch the surface with being studied at a single level, rather than from a sys-tematic perspective of the whole.Aim: The purpose of this study was to explore the underlying mechanisms of JCJ in treating AFC from the perspectives of fecal metabolites and related pathways, gut microbiota, key gene targets and functional path-ways, as well as "behaviors-microbiota-metabolites" relationships.Methods: 16S rRNA analysis and fecal metabolomics combined with network pharmacology were applied to investigate the abnormal performances of AFC rats, as well as the regulatory effects of JCJ. Results: JCJ significantly regulated the abnormalities of rats' behaviors, the microbial richness, and the metab-olite profiles that were interrupted by AFC. 19 metabolites were found to be significantly associated with AFC involving in 15 metabolic pathways. Delightfully, JCJ significantly regulated 9 metabolites and 6 metabolic pathways. AFC significantly interrupted the levels of 4 differential bacteria while JCJ significantly regulated the level of SMB53. HSP90AA1 and TP53 were the key genes, and pathways in cancer was the most relevant signaling pathways involving in the mechanisms of JCJ.Conclusion: The current findings not only reveal that the occurrence of AFC is closely related to gut microbiota mediating amino acid and energy metabolism, but also demonstrate the effects and the underlying mechanisms of JCJ on AFC.