Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients

Caroline Himbert; W Zac Stephens; Biljana Gigic; Sheetal Hardikar; Andreana N Holowatyj; Tengda Lin; Jennifer Ose; Eric Swanson; Anjelica Ashworth; Christy A Warby; Anita R Peoples; David Nix; Jolanta Jedrzkiewicz; Mary Bronner; Bartley Pickron; Courtney Scaife; Jessica N Cohan; Petra Schrotz-King; Nina Habermann; Juergen Boehm; Meredith Hullar; Jane C Figueiredo; Adetunji T Toriola; Erin M Siegel; Christopher I Li; Alexis B Ulrich; David Shibata; Kenneth Boucher; Lyen C Huang; Martin Schneider; June L Round; Cornelia M Ulrich

Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients

Am J Cancer Res. 2022 Oct 15;12(10):4789-4801. eCollection 2022.

Authors

Caroline Himbert^{1

2}, W Zac Stephens¹, Biljana Gigic³, Sheetal Hardikar^{1

2}, Andreana N Holowatyj^{1

4}, Tengda Lin^{1

2}, Jennifer Ose^{1

2}, Eric Swanson⁵, Anjelica Ashworth², Christy A Warby², Anita R Peoples^{1

2}, David Nix^{1

2}, Jolanta Jedrzkiewicz^{1

2}, Mary Bronner^{1

2}, Bartley Pickron^{1

2}, Courtney Scaife^{1

2}, Jessica N Cohan^{1

2}, Petra Schrotz-King⁶, Nina Habermann³, Juergen Boehm², Meredith Hullar⁷, Jane C Figueiredo⁸, Adetunji T Toriola⁹, Erin M Siegel¹⁰, Christopher I Li⁷, Alexis B Ulrich³, David Shibata¹¹, Kenneth Boucher^{1

2}, Lyen C Huang^{1

2}, Martin Schneider³, June L Round¹, Cornelia M Ulrich^{1

2}

Affiliations

¹ University of Utah Salt Lake City, UT, USA.
² Huntsman Cancer Institute Salt Lake City, UT, USA.
³ University Hospital Heidelberg Germany.
⁴ Vanderbilt University Medical Center Nashville, TN, USA.
⁵ Scripps Health San Diego, CA, USA.
⁶ National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ) Germany.
⁷ Fred Hutchinson Cancer Research Center Seattle, WA, USA.
⁸ Cedars-Sinai Medical Center Los Angeles, CA, USA.
⁹ Washington University School of Medicine St. Louis, MO, USA.
¹⁰ H. Lee Moffitt Cancer Center & Research Institute Tampa, FL, USA.
¹¹ University of Tennessee Health Science Center Memphis, TN, USA.

PMID: 36381318
PMCID: PMC9641409

Abstract

Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients. N=179 patients with colorectal cancer (stages I-IV) were included in the study. Pre-surgery stool samples were used to perform 16S rRNA gene sequencing (Illumina). Physical activity (MET hrs/wk) during the year before diagnosis was assessed by questionnaire and participants were classified as being active vs. inactive based on guidelines. BMI at baseline was abstracted from medical records. Patients were classified into four combinations of physical activity levels/BMI. Lower gut microbial diversity was observed among 'inactive' vs. 'active' patients (Shannon: P=0.01, Simpson: P=0.03), 'obese' vs. 'normal weight' patients (Shannon, Simpson, and Observed species: P=0.02, respectively), and 'overweight/obese/inactive' vs. 'normal weight/active' patients (Shannon: P=0.02, Observed species: P=0.04). Results differed by sex and tumor site. Two phyla and 12 genera (Actinobacteria and Fusobacteria, Adlercreutzia, Anaerococcus, Clostridium, Eubacterium, Mogibacteriaceae, Olsenella, Peptinophilus, Pyramidobacter, RFN20, Ruminococcus, Succinivibrio, Succiniclasticum) were differentially abundant across physical activity and BMI groups. This is the first evidence for associations of physical activity with gut microbiome diversity and abundances, directly among colorectal cancer patients. Our results indicate that physical activity may offset gut microbiome dysbiosis due to obesity. Alterations in gut microbiota may contribute mechanistically to the energy balance-colorectal cancer link and impact clinical outcomes.

Keywords: Colorectal cancer; energy balance; microbiome; obesity; physical activity.

Abstract

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