Oral/gut microbiome and inflammatory markers in African American colon cancer patients

Abstract

Background: Colorectal cancer (CRC) is the third leading cause of cancer deaths in the US, with African American (AA) patients having the highest incidence and mortality rate. Periodontitis, a chronic oral inflammatory condition, increases the risk of CRC. Fusobacterium nucleatum (Fn), a periodontal pathogen, has been implicated in CRC pathogenesis by altering gut microbiota composition and promoting inflammation. Our study explored the complex interplay between the immune response and the microbiome as it relates to colon cancer in AA patients. Methods: Our study included qPCR analysis, 16S rRNA gene sequencing, and RNA sequencing of tumor vs. non-tumor tissues, analysis of inflammatory mediators by using a quantitative slidebased array and antibody responses to specific bacteria by novel protein microarray NAPPA in serum, and immunohistochemistry staining to quantify T cell subset densities in tumors. Results: Our analysis revealed a distinct microbial profile in colon tumor tissues, characterized by reduced microbial diversity and increased oral-origin bacterial abundance. Right-sided tumors revealed distinct inflammation and immune responses, in contrast to metabolic and signaling expression pathways in left tumors. Fn was significantly increased in tumors (p= 0.0003) and was associated with gut microbiota changes by co-aggregating with other oral pathogens and reducing probiotic and CRC-associated bacteria. Upregulated pathways in Fn-positive tumors were neutrophil chemotaxis, NF-κB, TLR signaling and Wnt signaling, and T cell differentiation with increased CD8+ T cell density within the tumor (p=0.036). Additionally, patients with early-stage and right-sided tumors exhibited higher anti-Fn seropositivity (p< 0.00001). Conclusions: Our study reveals unique microbial and immunological profiles in AAs with colon cancer. These findings offer insights into genetic pathways and possible microbial contributions across different colon tumor locations and cancer stages, highlighting the need for further investigation into underlying mechanisms and potential new therapeutic targets.