Oral Microbiome and CPT1A Function in Fatty Acid Metabolism in Oral Cancer

• Published in: International journal of molecular sciences 2024-10, Vol.25 (20), p.10890
• Main Authors: Praveen, Zeba, Choi, Sung-Weon, Lee, Jong Ho, Park, Joo Yong, Oh, Hyun Jun, Kwon, Ik Jae, Park, Jin Hee, Kim, Mi Kyung
• Format: Article
• Language: English
• Subjects: Accuracy; Adenosine triphosphatase; Adult; Aged; Analysis; B cells; Bacteria; Biomarkers; Cancer; Carnitine; Carnitine O-Palmitoyltransferase - genetics; Carnitine O-Palmitoyltransferase - metabolism; Case-Control Studies; Cytokines; Dehydrogenases; Disease; Dysbiosis - metabolism; Dysbiosis - microbiology; Enzymes; Ethylenediaminetetraacetic acid; Fatty acids; Fatty Acids - metabolism; Female; Humans; Interleukins; Kinases; Ligases; Male; Medical prognosis; Metabolism; Metabolites; Microbiota; Middle Aged; Mortality; Mouth - metabolism; Mouth - microbiology; Mouth cancer; Mouth Neoplasms - metabolism; Mouth Neoplasms - microbiology; Oncology, Experimental; Oral cancer; Oxidative stress; Patients; Ribosomal RNA; RNA, Ribosomal, 16S - genetics; Saliva - metabolism; Saliva - microbiology; Survival analysis; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252010890

The oral microbiome is crucial for human health. Although oral dysbiosis may contribute to oral cancer (OC), the detailed relationships between the microbiome and OC remain unclear. In this case-control study, we aimed to elucidate the connection between the oral microbiome and mechanisms potentially involved in oral cancer. The study analyzed 1022 oral saliva samples, including 157 from oral cancer patients and 865 from healthy controls, using 16S ribosomal RNA (16S rRNA) sequencing and a Light Gradient Boosting Machine (LightGBM) model to identify four bacterial genera significantly associated with oral cancer. In patients with oral cancer, the relative abundance of and was higher; and showed decreased relative abundance; and levels of fatty acid oxidation enzymes, including Carnitine palmitoyltransferase 1A (CPT1A), long-chain acyl-CoA synthetase, acyl-CoA dehydrogenase, diacylglycerol choline phosphotransferase, and H+-transporting ATPase, were significantly higher compared to controls. Conversely, healthy controls exhibited increased levels of short-chain fatty acids (SCFAs) and CD4+T-helper cell counts. Survival analysis revealed that higher abundance of and , which correlated positively with interleukin-6, tumor necrosis factor-alpha, and CPT1A, were linked to poorer disease-free survival (DFS) and overall survival (OS) rates, while and were associated with better outcomes. These findings suggest that changes in these bacterial genera are associated with alterations in specific cytokines, CPT1A levels, SCFAs in oral cancer, with lower SCFA levels in patients reinforcing this link. Overall, these microbiome changes, along with cytokine and enzyme alterations, may serve as predictive markers, enhancing diagnostic accuracy for oral cancer.