Survival implications of the age-associated tumor and normal adjacent tissue microbiome among colorectal cancer patients

Maria F Gomez Morales; Stephanie R Hogue; Scott Pitcher; Daniel Jeong; Ivana Radosavljevic; Amalia Stefanou; Seth I Felder; Jessica R Burns; Scot E Dowd; Emily Vogtmann; Rashmi Sinha; Liang Wang; Xuefeng Wang; Jennifer B Permuth; Cynthia L Sears; Shaneda Warren Andersen; K Leigh Greathouse; Jacob K Kresovich; Mark S Friedman; Erin M Siegel; Doratha A Byrd

doi:10.1186/s13099-025-00773-6

Survival implications of the age-associated tumor and normal adjacent tissue microbiome among colorectal cancer patients

Gut Pathog. 2025 Dec 23;17(1):109. doi: 10.1186/s13099-025-00773-6.

Authors

Maria F Gomez Morales^{1

2}, Stephanie R Hogue³, Scott Pitcher¹, Daniel Jeong^{4

5}, Ivana Radosavljevic¹, Amalia Stefanou⁴, Seth I Felder⁴, Jessica R Burns³, Scot E Dowd⁶, Emily Vogtmann⁷, Rashmi Sinha⁷, Liang Wang⁸, Xuefeng Wang⁸, Jennifer B Permuth^{1

4}, Cynthia L Sears⁹, Shaneda Warren Andersen^{10

11}, K Leigh Greathouse^{12

13}, Jacob K Kresovich¹, Mark S Friedman⁴, Erin M Siegel¹, Doratha A Byrd^{14

15}

Affiliations

¹ Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
² College of Public Health, University of South Florida, Tampa, FL, US.
³ Non-Therapeutic Research Office, Moffitt Cancer Center, Tampa, FL, US.
⁴ Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, US.
⁵ Department of Radiology, Moffitt Cancer Center, Tampa, FL, US.
⁶ Mr. DNA Molecular Research Laboratory, Shallowater, TX, US.
⁷ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, US.
⁸ Department of Bioinformatics, Informatics, and Biostatistics, Moffitt Cancer Center, Tampa, FL, US.
⁹ Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Medicine and the Bloomberg School of Public Health, Baltimore, MD, US.
¹⁰ Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, 610 Walnut St, WARF Office Building, Madison, WI, 53726, US.
¹¹ University of Wisconsin Carbone Cancer Center, Madison, WI, 53726, USA.
¹² Human Science and Design, Robbins College of Health and Human Sciences, Baylor University, Waco, TX, US.
¹³ Department of Biology, Baylor University, Waco, TX, US.
¹⁴ Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA. Doratha.Byrd@moffitt.org.
¹⁵ Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, US. Doratha.Byrd@moffitt.org.

Abstract

Background: CRC incidence is rising among individuals younger than 50 years of age, with significant gaps in our understanding of the composition of the tissue microbiome across the age spectrum. The microbiome of tumors and normal adjacent tissue among colorectal cancer (CRC) patients may provide critical insights into the tumor microenvironment and CRC prognosis.

Methods: We characterized the tumor and normal adjacent tissue microbiome of early-onset (EoCRC, n = 46) and frequency-matched later-onset (LoCRC, N = 101) CRC patients who underwent surgery at Moffitt Cancer Center. We extracted DNA from archival tissue from 147 patients and sequenced the 16 S rRNA gene. We estimated the relative abundance of a priori and exploratory bacteria and alpha and beta diversity. We used multivariable linear regression models to estimate the association of age with the tumor and normal adjacent tissue microbiome. Then, we estimated associations of primarily age-associated microbiome metrics with overall survival using multivariable Cox proportional hazard models.

Results: In normal adjacent tissue, for every 10-year increase in age, there was a 1-SD higher relative abundance of a priori-selected Porphyromonas (Beta = 0.14, P = 0.03), Peptostreptococcus (Beta = 0.14, P = 0.03), and Prevotella (Beta = 0.13, P = 0.04). Fusobacterium and Bacillus were more abundant among EoCRC cases than LoCRC cases. In turn, Prevotella was associated with a 47% higher risk of mortality per 1-SD increase (95% CI = 1.19, 1.81; P < 0.001). Fusobacterium was not associated with mortality, but Bacillus was inversely associated with mortality.

Conclusion: We found that age at diagnosis was associated with the relative abundance of several bacteria, including oral-origin genera that were previously CRC-associated, in CRC normal adjacent tissue. In turn, some of these bacteria were associated with survival, suggesting potential age-related mechanisms underlying associations of the microbiome with survival.

Translational relevance of the work: Emerging evidence has highlighted the important role of the microbiome in colorectal cancer (CRC). Since the 1990s, there has been an increase in cases of early-onset colorectal cancer. However, there is still a limited understanding of the risk factors contributing to this rise. Investigating the associations between the microbiome of tumors and normal adjacent tissue in relation to aging offers a unique perspective on potential modifiable factors. Notably, our study has shown that age-related changes in the abundance of bacteria originating from the oral cavity, such as Porphyromonas, Peptostreptococcus, and Prevotella, are linked to CRC prognosis. These findings suggest that changes in the tissue microbiome with age may serve as prognostic markers for CRC and could help inform future prevention strategies that consider dietary and oral health interventions.

Keywords: Age-associated microbiome changes; Early-onset colorectal cancer; Tissue microbiome.

Abstract

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