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Oral/gut microbiome and inflammatory markers in African American colon cancer patients
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Martello-Rooney, Laura
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2024-03-12
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Tortora thesis.pdf
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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.
Citation
Tortora-Morel, S (2024). Oral/gut microbiome and inflammatory markers in African American colon cancer patients [Doctoral dissertation, SUNY Downstate Health Sciences University]. SUNY Open Access Repository. https://soar.suny.edu/handle/20.500.12648/14767