Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in men

Mengyao Shi; Xiaoyu Zong; Jinhee Hur; Brenda M Birmann; Otoniel Martinez-Maza; Marta Epeldegui; Andrew T Chan; Edward L Giovannucci; Yin Cao

doi:10.1016/j.ebiom.2023.104566

Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in men

EBioMedicine. 2023 May:91:104566. doi: 10.1016/j.ebiom.2023.104566. Epub 2023 Apr 17.

Authors

Mengyao Shi¹, Xiaoyu Zong¹, Jinhee Hur², Brenda M Birmann³, Otoniel Martinez-Maza⁴, Marta Epeldegui⁵, Andrew T Chan⁶, Edward L Giovannucci⁷, Yin Cao⁸

Affiliations

¹ Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
² Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, Gyeonggi, South Korea; Food Clinical Research Center, Institute of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi, South Korea.
³ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Department of Obstetrics and Gynecology, AIDS Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁶ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁸ Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: yin.cao@wustl.edu.

Abstract

Background: Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited.

Methods: We conducted a prospective, nested case-control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993-2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 (sCD14), and endotoxincore antibody (EndoCAb) immunoglobulin M (IgM), with subsequent risk of CRC. Unconditional logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Findings: Pre-diagnostic circulating levels of sCD14 were associated with a higher risk of incident CRC. Compared to men in the lowest quartile, the multivariable OR was 1.90 (95% CI, 1.13-3.22) for men in the highest quartile (OR _{per standard deviation [SD] increase}, 1.28; 95%CI 1.06-1.53; P_trend = 0.01). This positive association remained similar after adjusting for C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor-2, and within strata of putative CRC risk factors. We also observed a suggestive inverse association between EndoCAb IgM and risk of CRC (OR _{per SD increase}, 0.84; 95%CI 0.69-1.02; P_trend = 0.09).

Interpretation: Microbial translocation and host response to bacteria, as reflected by sCD14, is associated with risk of incident CRC in men.

Funding: US National Institutes of Health.

Keywords: Colorectal cancer; Gut dysbiosis; Microbial translocation.

MeSH terms

Bacteria
Case-Control Studies
Colorectal Neoplasms* / epidemiology
Colorectal Neoplasms* / etiology
Follow-Up Studies
Humans
Immunoglobulin M
Lipopolysaccharide Receptors*
Male
Prospective Studies
Risk Factors

Substances

Lipopolysaccharide Receptors
Immunoglobulin M

Abstract

MeSH terms

Substances

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