Thailand Hub of Talents in Cancer Immunotherapy (TTCI Thailand)

A groundbreaking study has delved into the potential interactions between cannabidiol (CBD) and CD19-chimeric antigen receptor (CAR) T cell therapy, a promising approach in cancer immunotherapy. The study aimed to explore the direct effects of CBD on the functionality of CD19-CAR T cells against hematologic malignancies.

This study investigates the fecal metabolic profiles associated with periductal fibrosis (PDF) and cholangiocarcinoma (CCA), a type of bile duct cancer primarily caused by the liver fluke Opisthorchis viverrini. The research, focusing on the Greater Mekong Subregion, especially northeast Thailand, where CCA incidence is notably high, aims to gain insights into metabolic changes for potential diagnostic marker development and further molecular research related to gut health.

Methods:
Nuclear magnetic resonance (NMR) metabolomics was used for fecal metabolic phenotyping.
The study analyzed 55 fecal water samples from different groups: normal bile duct, PDF, and CCA.

Results:
NMR spectroscopy-based metabolomics identified 40 metabolites in the fecal profiles of patients with PDF or CCA, and individuals with normal bile ducts.
Multivariate statistical analysis and hierarchical clustering heat maps highlighted PDF- and CCA-specific metabotypes.
These metabotypes exhibited alterations in various metabolite groups: amino acids, alcohols, amines, anaerobic glycolytic metabolites, fatty acids, microbial metabolites, sugars, TCA cycle intermediates, tryptophan catabolism substrates, and pyrimidine metabolites.
Compared to normal bile duct individuals, those with PDF showed increased fecal concentrations of ethanol, glycine, tyrosine, and N-acetylglucosamine. In contrast, CCA patients displayed marked increases in uracil, succinate, and 5-aminopentanoate.
The most notable difference between CCA and PDF was a reduction in methanol concentration in CCA patients.
The metabolic changes suggest involvement of various pathways: TCA cycle, ethanol and methanol biogenesis, hexamine pathway, pyrimidine metabolism, and lysine metabolism. These reflect gut-microbial host metabolic interactions in PDF and/or CCA patients.

Conclusion:
Distinct fecal metabolic patterns were identified for PDF and CCA, different from those of normal bile ducts.
The study indicates that host-gut bacteria co-metabolism perturbation is involved from the early stages of Opisthorchis viverrini infection to CCA tumorigenesis.
These findings are significant for understanding the metabolic underpinnings of CCA and developing potential diagnostic markers.

Funding

This work was financially supported by the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation to Jutarop Phetcharaburanin (Grant number: RGNS63-051). The nuclear magnetic resonance spectroscopy platform was supported by the Basic Research Fund of Khon Kaen University under Cholangiocarcinoma Research Institute to Nisana Namwat (Grant number: 1500148). Rujikorn Treeriya received the studentship supported by Faculty of Medicine, Khon Kaen University (Grant number: RA108(2019)).

Original Paper

Title of original paper: 1H NMR fecal metabolic phenotyping of periductal fibrosis- and cholangiocarcinoma-specific metabotypes defining perturbation in gut microbial-host co-metabolism
Journal: PeerJ
DOI: 10.7717/peerj.15386

Correspondence