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      Dysbiosis of human gut microbiome in young-onset colorectal cancer

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          Abstract

          The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Through 16S rRNA gene sequencing, 728 samples are collected to identify microbial markers, and an independent cohort of 310 samples is used to validate the results. Furthermore, species-level and functional analysis are performed by metagenome sequencing using 200 samples. Gut microbial diversity is increased in yCRC. Flavonifractor plautii is an important bacterial species in yCRC, while genus Streptococcus contains the key phylotype in the old-onset colorectal cancer. Functional analysis reveals that yCRC has unique characteristics of bacterial metabolism characterized by the dominance of DNA binding and RNA-dependent DNA biosynthetic process. The random forest classifier model achieves a powerful classification potential. This study highlights the potential of the gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with yCRC.

          Abstract

          The incidence of young-onset sporadic colorectal cancer (yCRC) is rapidly rising and frequently associated with an aggressive disease. Here the authors show that gut microbial diversity is increased in patients with yCRC compared to old-onset CRC and that fecal microbial markers could be used to detect individuals with yCRC.

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          Most cited references64

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          Inflammaging: a new immune–metabolic viewpoint for age-related diseases

          Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation - called inflammaging - develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases.
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            Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.

            Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134,000 persons will be diagnosed with the disease, and about 49,000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 68 years.
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              Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society

              In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.
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                Author and article information

                Contributors
                yanleima@fudan.edu.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                19 November 2021
                19 November 2021
                2021
                : 12
                : 6757
                Affiliations
                [1 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Department of Colorectal Surgery, , Fudan University Shanghai Cancer Center, ; Shanghai, China
                [2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of Oncology, Shanghai Medical College, , Fudan University, ; Shanghai, China
                [3 ]GRID grid.452704.0, ISNI 0000 0004 7475 0672, Department of Clinical Laboratory, , The Second Hospital of Shandong University, ; 250033 Jinan, Shandong province China
                [4 ]GRID grid.412538.9, ISNI 0000 0004 0527 0050, Department of GI Surgery, , Shanghai Tenth People’s Hospital Affiliated to Tongji University, ; Shanghai, China
                [5 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Department of Endoscopy, , Fudan University Shanghai Cancer Center, ; Shanghai, China
                [6 ]Quantum Hi-Tech Microecological Medical (Guangdong) Co.,Ltd., Guangzhou, China
                Author information
                http://orcid.org/0000-0002-0632-5258
                Article
                27112
                10.1038/s41467-021-27112-y
                8604900
                34799562
                4e4a5726-02c4-464c-8ccb-d6eae101c12e
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 September 2020
                : 2 November 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: Nos. 81920108026, 81871964, 81802412
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100012543, Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Development Fund);
                Award ID: No.19410713300
                Award Recipient :
                Categories
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                Custom metadata
                © The Author(s) 2021

                Uncategorized
                colorectal cancer
                Uncategorized
                colorectal cancer

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