Intestinal Bacteria Fluctuating in Early-Stage Colorectal Cancer Carcinogenesis are Associated with Diet in Healthy Adults

Abstract

This hospital-based, cross-sectional study aimed to explore the association between diet and fluctuating intestinal bacteria in early-stage colorectal cancer (CRC) (Atopobium parvulum, Actinomyces odontolyticus, Solobacterium moorei, and Bifidobacterium longum). Healthy participants (n = 212) who underwent total colonoscopy at National Cancer Center Hospital (Tokyo, Japan) were divided into two groups according to the relative abundance of bacteria in their feces: those in the top 25% of relative bacterial abundance as cases and the bottom 25% as controls. The participants were divided into three groups (low, medium, and high) according to their intake of food groups associated with CRC. Multivariable logistic regression analysis was conducted to estimate the association between dietary intake and higher relative abundance of bacteria. Dairy products were inversely associated with a higher relative abundance of A. parvulum, A. odontolyticus, and S. moorei, with odds ratios (high vs. low) and 95% confidence interval as follows: 0.16 (0.06–0.44), 0.25 (0.08–0.82), and 0.29 (0.11–0.78), respectively. Additionally, dietary fiber was inversely associated with a higher relative abundance of S.moorei (0.29 [0.11–0.78]). No association was observed between diet and B.longum. In conclusion, healthy adults with a higher intake of dairy products and fiber had lower odds of having a higher relative abundance of CRC-associated microbiota.

Acknowledgments

We thank our colleagues at the Osaka University Center of Medical Data Science and the Advanced Clinical Epidemiology Investigator’s Research Project for providing insights and expertise.

Authors’ Contributions

N.N., L.Z., T.S., T.K., T.Y., and S.Y. contributed to the study concept and design. S.S., S.M., T.Y., and S.Y. collected the clinical samples and metagenomic information and prepared the dataset. N.N. and L.Z. performed statistical analyses. N.N. drafted the manuscript. All authors critically revised the manuscript. T. S. supervised the study.

Disclosure Statement

Yamada founded Metagen Inc., Metagen Therapeutics Inc., and Digzyme Inc. These companies had no control over the interpretation, writing, or publication of this manuscript. The other authors declare no conflict of interest.

Data Availability Statement

The raw sequencing data reported in this study were deposited in the DDBJ Sequence Read Archives (DRA) as DRA006684 and DRA008156.

Additional information

Funding

S. Yachida was supported by grants from the National Cancer Center Research and Development Fund (2020-A-4), JSPS KAKENHI (JP20H033620), Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED) (JP21ck0106546), Project for Cancer Research and Therapeutic Evolution (P-CREATE) from AMED (JP22cm0106477), United States-Japan Cooperative Medical Science Program from AMED (JP20jk0210009), AIP Accelerated Program from JST (21-191029679); Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Joint Research Project of the Institute Medical Science, the University of Tokyo, the Takeda Science Foundation, the Yasuda Medical Foundation, the Mitsubishi Foundation, and the Princess Takamatsu Cancer Research Fund.