1 H NMR fecal metabolic phenotyping of periductal fibrosis- and cholangiocarcinoma-specific metabotypes defining perturbation in gut microbial-host co-metabolism

PeerJ

article

Rujikorn Treeriya¹  Phuc N. Ho¹  Attapol Titapun²  Poramate Klanrit³  Manida Suksawat³  Thanaporn Kulthawatsiri³  Suphasarang Sirirattanakul³  Watcharin Loilome³  Nisana Namwat³  Arporn Wangwiwatsin³  Nittaya Chamadol³  Narong Khuntikeo²  Jutarop Phetcharaburanin³ 

[1] Department of Biochemistry, Faculty of Medicine, Khon Kaen University;Department of Surgery, Faculty of Medicine, Khon Kaen University;Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University;Khon Kaen University Phenome Centre, Faculty of Medicine, Khon Kaen University;Department of Systems Biosciences and Computational Medicine, Faculty of Medicine, Khon Kaen University;Department of Radiology, Faculty of Medicine, Khon Kaen University;Center of Excellence for Innovation in Chemistry ,(PERCH-CIC), Faculty of Science, Khon Kaen University

关键词: Metabolomics;    Periductal fibrosis;    Cholangiocarcinoma;    Nuclear magnetic resonance spectroscopy;   

DOI  :  10.7717/peerj.15386

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background The liver fluke Opisthorchis viverrini (OV), which subsequently inhabits the biliary system and results in periductal fibrosis (PDF), is one of the primarily causes of cholangiocarcinoma (CCA), a bile duct cancer with an exceptionally high incidence in the northeast of Thailand and other Greater Mekong Subregion (GMS) countries. Insights in fecal metabolic changes associated with PDF and CCA are required for further molecular research related to gut health and potential diagnostic biological marker development. Methods In this study, nuclear magnetic resonance (NMR) metabolomics was applied for fecal metabolic phenotyping from 55 fecal water samples across different study groups including normal bile duct, PDF and CCA groups. Results By using NMR spectroscopy-based metabolomics, fecal metabolic profiles of patients with CCA or PDF and of individuals with normal bile duct have been established with a total of 40 identified metabolites. Further multivariate statistical analysis and hierarchical clustering heat map have demonstrated the PDF- and CCA-specific metabotypes through various altered metabolite groups including amino acids, alcohols, amines, anaerobic glycolytic metabolites, fatty acids, microbial metabolites, sugar, TCA cycle intermediates, tryptophan catabolism substrates, and pyrimidine metabolites. Compared to the normal bile duct group, PDF individuals showed the significantly elevated relative concentrations of fecal ethanol, glycine, tyrosine, and N-acetylglucosamine whereas CCA patients exhibited the remarkable fecal metabolic changes that can be evident through the increased relative concentrations of fecal uracil, succinate, and 5-aminopentanoate. The prominent fecal metabolic alterations between CCA and PDF were displayed by the reduction of relative concentration of methanol observed in CCA. The metabolic alterations associated with PDF and CCA progression have been proposed with the involvement of various metabolic pathways including TCA cycle, ethanol biogenesis, hexamine pathway, methanol biogenesis, pyrimidine metabolism, and lysine metabolism. Among them, ethanol, methanol, and lysine metabolism strongly reflect the association of gut-microbial host metabolic crosstalk in PDF and/or CCA patients. Conclusion The PDF- and CCA-associated metabotypes have been investigated displaying their distinct fecal metabolic patterns compared to that of normal bile duct group. Our study also demonstrated that the perturbation in co-metabolism of host and gut bacteria has been involved from the early step since OV infection to CCA tumorigenesis.

【 授权许可】

CC BY