Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in context
Summary: 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 eviden...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423001317 |
| _version_ | 1797845097941827584 |
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| author | Mengyao Shi Xiaoyu Zong Jinhee Hur Brenda M. Birmann Otoniel Martinez-Maza Marta Epeldegui Andrew T. Chan Edward L. Giovannucci Yin Cao |
| author_facet | Mengyao Shi Xiaoyu Zong Jinhee Hur Brenda M. Birmann Otoniel Martinez-Maza Marta Epeldegui Andrew T. Chan Edward L. Giovannucci Yin Cao |
| author_sort | Mengyao Shi |
| collection | DOAJ |
| description | Summary: 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; Ptrend = 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; Ptrend = 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. |
| first_indexed | 2024-04-09T17:33:03Z |
| format | Article |
| id | doaj.art-e9c3f15fadf84ca8a989ef59f19a7855 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-09T17:33:03Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-e9c3f15fadf84ca8a989ef59f19a78552023-04-18T04:08:47ZengElsevierEBioMedicine2352-39642023-05-0191104566Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in contextMengyao Shi0Xiaoyu Zong1Jinhee Hur2Brenda M. Birmann3Otoniel Martinez-Maza4Marta Epeldegui5Andrew T. Chan6Edward L. Giovannucci7Yin Cao8Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USADivision of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USADepartment 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 KoreaChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USADepartment 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, USADepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USAChanning 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, USADepartment 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, USADivision 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; Corresponding author. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8100, St. Louis, MO, 63110, USA.Summary: 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; Ptrend = 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; Ptrend = 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.http://www.sciencedirect.com/science/article/pii/S2352396423001317Colorectal cancerMicrobial translocationGut dysbiosis |
| spellingShingle | Mengyao Shi Xiaoyu Zong Jinhee Hur Brenda M. Birmann Otoniel Martinez-Maza Marta Epeldegui Andrew T. Chan Edward L. Giovannucci Yin Cao Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in context EBioMedicine Colorectal cancer Microbial translocation Gut dysbiosis |
| title | Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in context |
| title_full | Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in context |
| title_fullStr | Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in context |
| title_full_unstemmed | Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in context |
| title_short | Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in menResearch in context |
| title_sort | circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer a prospective nested case control study in menresearch in context |
| topic | Colorectal cancer Microbial translocation Gut dysbiosis |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423001317 |
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