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

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 Streptococcus and Parvimonas was higher; Corynebacterium and Prevotella 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 Streptococcus and Parvimonas, 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 Prevotella and Corynebacterium 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.

Exploring Connections between Oral Microbiota, Short-Chain Fatty Acids, and Specific Cancer Types: A Study of Oral Cancer, Head and Neck Cancer, Pancreatic Cancer, and Gastric Cancer.

The association between oral microbiota and cancer development has been a topic of intense research in recent years, with compelling evidence suggesting that the oral microbiome may play a significant role in cancer initiation and progression. However, the causal connections between the two remain a subject of debate, and the underlying mechanisms are not fully understood. In this case-control study, we aimed to identify common oral microbiota associated with several cancer types and investigate the potential mechanisms that may trigger immune responses and initiate cancer upon cytokine secretion. Saliva and blood samples were collected from 309 adult cancer patients and 745 healthy controls to analyze the oral microbiome and the mechanisms involved in cancer initiation. Machine learning techniques revealed that six bacterial genera were associated with cancer. The abundance of Leuconostoc, Streptococcus, Abiotrophia, and Prevotella was reduced in the cancer group, while abundance of Haemophilus and Neisseria enhanced. G protein-coupled receptor kinase, H+-transporting ATPase, and futalosine hydrolase were found significantly enriched in the cancer group. Total short-chain fatty acid (SCFAs) concentrations and free fatty acid receptor 2 (FFAR2) expression levels were greater in the control group when compared with the cancer group, while serum tumor necrosis factor alpha induced protein 8 (TNFAIP8), interleukin-6 (IL6), and signal transducer and activator of transcription 3 (STAT3) levels were higher in the cancer group when compared with the control group. These results suggested that the alterations in the composition of oral microbiota can contribute to a reduction in SCFAs and FFAR2 expression that may initiate an inflammatory response through the upregulation of TNFAIP8 and the IL-6/STAT3 pathway, which could ultimately increase the risk of cancer onset.