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Cited by 752Gut microbiota and healthNutritional Studies and DietColorectal Cancer Screening and Detection

Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer

Open access
Song, Mingyang, Chan, Andrew T., Sun, Jun·2020·Gastroenterology
DOI 10.1053/j.gastro.2019.06.048PMC PMC6957737
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Abstract

Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.

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Crossref · 10.1053/j.gastro.2019.06.048

Cites

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Statistics

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Claims the paper makes

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  • Premisecitation

    About 50%-60% of incident colorectal cancer cases in the United States are estimated to be attributable to modifiable risk factors.

    “Approximately 50%–60% of incident cases of CRC in the US are estimated to be attributable to modifiable risk factors4, 5”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Islami, 2018, Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States, CA Cancer J Clin

      Not checked in the free run.

    • cites [5] Mima, 2016, Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location, Clin Transl Gastroenterol source

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  • Interpretationreasoning

    Changes in the intestinal microbiome can mediate or modify how environmental factors affect colorectal cancer risk.

    “Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Specific microbiome and metabolome changes occur across stages of colorectal neoplasia, from adenomatous polyps to early cancer to metastatic disease.

    “Specific changes in the microbiome and metabolome occur during different stages of colorectal neoplasia, from adenomatous polyps to early-stage cancer to metastatic disease, supporting an etiological and diagnostic role for the microbiome.18–20”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18] Feng, 2015, Gut microbiome development along the colorectal adenoma-carcinoma sequence, Nat Commun source

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    • cites [19] Nakatsu, 2015, Gut mucosal microbiome across stages of colorectal carcinogenesis, Nat Commun source

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    • cites [20] Yachida, 2019, Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer, Nat Med source

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  • Premisecitation

    Fusobacterium nucleatum levels in tumor tissue are associated with lower T cell infiltration.

    “Moreover, levels of F nucleatum in tumor tissue have been associated with lower infiltration by T cells,29, 30”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Nosho, 2016, Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer, World J Gastroenterol source

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    • cites [30] Mima, 2015, Fusobacterium nucleatum and T cells in colorectal carcinoma, JAMA Oncol source

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  • Premisecitation

    Associations have been found between components of the intestinal microbiome and colorectal cancer risk.

    “Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Song, 2019, Environmental factors, gut microbiota, and colorectal cancer prevention, Clin Gastroenterol Hepatol source

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    • cites [7] Scott, 2019, International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis, Gut source

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  • Classified as probably not a substantial claim. 7

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    Premisecitation

    Fusobacterium nucleatum is associated with right-sided anatomic location, BRAF mutations, and hypermutation with microsatellite instability.

    “Epidemiologic studies of patients with CRC or premalignant lesions have associated F nucleatum with specific clinical and molecular features, such as right-sided anatomic location, mutations in BRAF, and hypermutation with microsatellite instability.24–27”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [24] Ito, 2015, Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway, Int J Cancer source

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    • cites [25] Li, 2016, Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients, World J Gastroenterol source

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  • May combine two claims.

    Premisenone given

    Studies have found differences in intestinal microbiome composition between colorectal cancer cases and healthy controls, and individual microbes enriched or depleted in colorectal cancer patients.

    “Studies have identified differences in compositions of intestinal microbiomes between CRC cases and healthy individuals (controls) as well as individual microbes that are enriched or depleted in microbiomes of patients with CRC.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Evidence indicates that gut microbiome changes occur during early colorectal carcinogenesis and can identify individuals at risk for colorectal adenoma.

    “Moreover, there is evidence that changes in the gut microbiome occur during early stages of colorectal carcinogenesis and can be used to identify individuals at risk for colorectal adenoma, the precursor lesion to CRC.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Changes in the microbiome may affect metabolism and immune function.

    “This could be because changes of the microbiome affect metabolism and immune function.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Features of the intestinal microbiome might be used for colorectal cancer screening and modified for chemoprevention and treatment.

    “Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A meta-analysis of metagenomic data found higher richness in colorectal cancer microbiomes than controls, partly from expansions of species typically from the oral cavity.

    “However, a meta-analysis of metagenomic data from different cohorts and populations found higher richness in microbiomes of CRC than controls, partly due to expansions of species typically derived from the oral cavity.16, 17”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Thomas, 2019, Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation, Nat Med source

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    • cites [17] Sze, 2018, Leveraging existing 16S rRNA gene surveys to identify reproducible biomarkers in individuals with colorectal tumors, MBio source

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  • May combine two claims.

    Interpretationreasoning

    Microbiome changes might be used as biomarkers for early colorectal cancer detection and to improve screening.

    “Changes in the microbiome might therefore be used as biomarkers for early detection of CRC, to improve screening strategies.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Higher Fusobacterium nucleatum abundance, present in about 10%-15% of tumors, is associated with advanced disease stage, higher recurrence risk, and shorter survival.

    “a higher abundance of F nucleatum (present in approximately 10%–15% of tumors) has been associated with advanced disease stage, higher risk of recurrence, and shorter patient survival times.23, 26, 28”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [23] Flanagan, 2014, Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome, Eur J Clin Microbiol Infect Dis source

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    • cites [26] Mima, 2016, Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis, Gut source

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    • cites [28] Yu, 2017, Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy, Cell source

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    Premisecitation

    Higher proportions of late-stage versus early-stage and right-side versus left-side tumors were enterotoxigenic Bacteroides fragilis positive.

    “Significantly higher proportions of late-stage vs early stage, and of right-side vs left-side, tumors were ETBF positive.40, 43”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [40] Boleij, 2015, The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients, Clin Infect Dis source

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    • cites [43] Viljoen, 2015, Quantitative profiling of colorectal cancer-associated bacteria reveals associations between Fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer, PLoS One source

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    Premisecitation

    In colorectal cancer patients, Escherichia coli invade the colonic mucosa and become intracellular.

    “In patients with CRC, E coli invade the colonic mucosa and become intracellular.47, 48”
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    • cites [47] Swidsinski, 1998, Association between intraepithelial Escherichia coli and colorectal cancer, Gastroenterology source

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    Premisecitation

    Enterotoxigenic Bacteroides fragilis abundance in fecal samples is lower than in mucosa because it colonizes colon epithelial crypts.

    “Compared to mucosa, the abundance of ETBF in fecal samples is lower, because ETBF colonizes colon epithelial crypts.40, 44”
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    • cites [40] Boleij, 2015, The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients, Clin Infect Dis source

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    • cites [44] Toprak, 2006, A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer, Clin Microbiol Infect source

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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Escherichia coli may not be shed into feces because they colonize the mucosa and reside within intestinal cells rather than the lumen.

    “This might be because E coli colonize the mucosa and reside within intestinal cells, rather than the lumen, so they are not shed into feces.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Smokers have decreased relative abundance of Neisseria and increased relative abundance of Veillonellaceae.

    “Smokers have a decreased relative abundance of Neisseria and increased relative abundance of Veillonellaceae families.58”
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    • cites [58] Kato, 2016, Oral microbiome and history of smoking and colorectal cancer, J Epidemiol Res

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    Premisecitation

    Escherichia coli strains with the pks gene, which mediates colibactin production, are found at higher frequency in individuals with colorectal cancer than without, in tumors than adjacent non-tumor tissue, and in late-stage than early-stage tumors.

    “E coli strains with the polyketide synthase gene complex (pks) gene, which mediates production of genotoxin colibactin (called pks+ E coli), are found at higher frequency in individuals with than without CRC,49–52 in tumors than in adjacent non-tumor tissue,51 and in late-stage tumors compared with early-stage tumors.51”
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    • cites [49] Arthur, 2012, Intestinal inflammation targets cancer-inducing activity of the microbiota, Science source

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    Interpretationcitation

    Alterations to the oral and intestinal microbiomes might each contribute to colorectal carcinogenesis through microbe dissemination and induction of inflammation.

    “So, alterations to the oral and intestinal microbiomes might each contribute to colorectal carcinogenesis, via microbe dissemination and induction of inflammation.54, 55, 59,60.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [54] Yang, 2019, Prospective study of oral microbiome and colorectal cancer risk in low-income and African American populations, Int J Cancer source

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    Premisecitation

    Smoking and dietary iron were identified as potential risk factors, indicating a link between non-typhoid Salmonella infection and intestinal tumorigenesis.

    “Smoking and dietary iron were identified as potential risk factors, indicating a link between non-typhoid Salmonella infection and intestinal tumoigenesis69.”
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    • cites [69] Kato, 2013, Partial associations of dietary iron, smoking and intestinal bacteria with colorectal cancer risk, Nutr Cancer source

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    Premisecitation

    The proportions of enterotoxigenic Bacteroides fragilis-positive colorectal tumors differed between studies, 26% versus 89%, possibly due to assay or sample processing differences.

    “However, the proportions of ETBF-positive colorectal tumors differed between these studies (26% vs 89%), possibly due to the differences in assays or sample processing methods.40”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Boleij, 2015, The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients, Clin Infect Dis source

      Not checked in the free run.

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    Premisecitation

    Individuals with the highest level of physical activity have a 19% lower risk of colon cancer than those with the lowest level, but physical activity has not been associated with rectal cancer.

    “Individuals with the highest level of physical activity have a 19% lower risk of colon cancer than individuals with the lowest level, but physical activity has not been associated with rectal cancer.78”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [78] World Cancer Research Fund, American Institute for Cancer Research. Diet, nutrition, physical activity and colorectal cancer; 2017. Available at: https://www.wcrf.org/sites/default/files/Colorectal-Cancer-2017-Report.pdf. Accessed October 18, 2019.

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    Premisecitation

    Akkermansia muciniphila correlated with better metabolic parameters, including lower fasting plasma glucose, lower plasma triglycerides, and improved insulin response.

    “The bacteria correlated with better metabolic parameters, including lower fasting level of plasma glucose, lower level of plasma triglycerides, and improved insulin response.100”
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    • cites [100] Shoaie, 2015, Quantifying diet-induced metabolic changes of the human gut microbiome, Cell Metab source

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    Premisecitation

    Ecological analysis revealed more co-exclusive correlations between fungi and bacteria in fecal samples from colorectal cancer patients than controls, supporting preclinical findings of an antagonistic relationship between bacteria and fungi during colorectal cancer development.

    “Ecological analysis revealed more co-exclusive correlations between fungi and bacteria in fecal samples from patients with CRC than controls,73 supporting the preclinical findings for an antagonistic relationship between bacteria and fungi during CRC development.75”
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    • cites [73] Coker, 2019, Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer, Gut source

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    • cites [75] Malik, 2018, SYK-CARD9 signaling axis promotes gut fungi-mediated inflammasome activation to restrict colitis and colon cancer, Immunity source

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    Premisecitation

    Compared with controls, colorectal cancer cases had increased diversity in bacteriophage viromes, associated with reduced bacterial diversity, and modest enrichment of specific viral taxa such as Inovirus and Tunalikevirus.

    “Compared to controls, CRC cases had increased diversity in bacteriophage viromes, associated with reduced bacterial diversity, and modest enrichment of specific viral taxa, such as members of Inovirus and Tunalikevirus, whose bacterial hosts have been implicated in CRC”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [72] Nakatsu, 2018, Alterations in enteric virome are associated with colorectal cancer and survival outcomes, Gastroenterology source

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    • cites [74] Hannigan, 2018, Diagnostic potential and interactive dynamics of the colorectal cancer virome, MBio source

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    Premisecitation

    Distinct mycobiome profiles were identified in colorectal cancer patients versus controls and in early- versus late-stage colorectal cancer.

    “Distinct mycobiome profiles were identified in patients with CRC vs controls and in patients with early- vs late-stage CRC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Coker, 2019, Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer, Gut source

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    Premisecitation

    A bidirectional Mendelian randomization analysis provided genetic evidence that increased intestinal short-chain fatty acid production improves insulin responses and reduces abnormalities in short-chain fatty acid production or absorption and risk of type 2 diabetes.

    “A bidirectional Mendelian randomization analysis provided genetic evidence that increased intestinal production of SCFAs improves patient responses to insulin and reduces abnormalities in the production or absorption of SCFAs and risk of type 2 diabetes.87”
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    • cites [87] Sanna, 2019, Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases, Nat Genet source

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    Premisecitation

    Higher body mass index is associated with increased blood levels of lipopolysaccharide and lipopolysaccharide-binding protein, whereas weight loss reduces circulating levels of both.

    “Higher BMIs have been associated with increased blood levels of LPS and LPS-binding protein (LBP), whereas weight loss reduces circulating LPS and LBP levels.102–104”
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    • cites [102] Yang, 2016, Circulating biomarkers of gut barrier function: correlates and nonresponse to calcium supplementation among colon adenoma patients, Cancer Epidemiol Biomarkers Prev source

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    • cites [104] Lassenius, 2011, Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation, Diabetes Care source

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    Premisecitation

    A cross-sectional study found that patients with adenomas had higher blood lipopolysaccharide levels than controls, and patients with villous adenomas had higher levels than patients with only tubular adenomas.

    “A cross-sectional study found that patients with adenomas had higher blood levels of LPS than controls, and that patients whose adenomas had villous features had higher levels of LPS than patients with only tubular adenomas.105”
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    • cites [105] Kang, 2013, Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas, BMC Cancer source

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    Premisecitation

    Bifidobacterium and Lactobacillus spp. produce lactate and acetate and can increase butyrate production through cross-feeding interactions with butyrate-producing species such as Eubacterium rectale.

    “Bifidobacterium and Lactobacillus spp. produce lactate and acetate and can also increase production of butyrate through cross-feeding interactions with the butyrate-producing species, such as Eubacterium rectale.130–132”
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    • cites [130] Flint, 2015, Links between diet, gut microbiota composition and gut metabolism, Proc Nutr Soc source

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    • cites [131] Belenguer, 2006, Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut, Appl Environ Microbiol source

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    • cites [132] Duncan, 2004, Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product, Appl Environ Microbiol source

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    Premisecitation

    Fiber supplementation enriched Bifidobacterium and Lactobacillus spp., with no effect on other common short-chain fatty acid producers except increases in Roseburia spp. and Faecalibacterium prausnitzii in parallel rather than crossover trials.

    “Fiber supplementation was found to enrich Bifidobacterium and Lactobacillus spp., whereas no effect was found on the other common SCFA producers except for increases in Roseburia spp. and F prausnitzii in parallel (rather than crossover) trials.”
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    • cites [128] So, 2018, Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis, Am J Clin Nutr source

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    Premisecitation

    Fiber is fermented by bacteria to produce short-chain fatty acids, which regulate the immune system and metabolism and reduce colorectal cancer risk.

    “Fiber is fermented by bacteria to produce SCFAs, which regulate the immune system and metabolism and reduce risk of CRC.6, 88, 94, 123–125”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [6] Song, 2019, Environmental factors, gut microbiota, and colorectal cancer prevention, Clin Gastroenterol Hepatol source

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    • cites [88] Koh, 2016, From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites, Cell source

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    • cites [94] Bultman, 2014, Molecular pathways: gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention, Clin Cancer Res source

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    • cites [123] Ploger, 2012, Microbial butyrate and its role for barrier function in the gastrointestinal tract, Ann N Y Acad Sci source

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    • cites [124] Makki, 2018, The impact of dietary fiber on gut microbiota in host health and disease, Cell Host Microbe source

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    • cites [125] Bhatt, 2017, The role of the microbiome in cancer development and therapy, CA Cancer J Clin

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    Interpretationcitation

    Differences in food sources of fiber between European and American diets and relatively low fiber intake in US cohorts might explain inconsistent results.

    “This might be due to differences in the food sources of fiber between European and American diets (mostly cereals vs fruits and vegetables) and the relatively low fiber intake in the US cohorts, which might not have achieved an effective threshold.3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Song, 2015, Nutrients, foods, and colorectal cancer prevention, Gastroenterology source

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    Premisecitation

    In some but not all randomized controlled trials, increased whole grain consumption was associated with higher abundance of short-chain fatty acid-producing bacteria such as Roseburia and Lachnospira, lower abundance of proinflammatory Enterobacteriaceae, and higher fecal short-chain fatty acid levels.

    “In some136, 137 but not all138, 139 randomized controlled trials, increased consumption of whole grains was associated with higher abundance of SCFA-producing bacteria, such as Roseburia and Lachnospira, lower abundance of proinflammatory Enterobacteriaceae, and higher levels of fecal SCFAs through anti-inflammaion.136”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [136] Vitaglione, 2015, Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber, Am J Clin Nutr source

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    • cites [137] Martinez, 2013, Gut microbiome composition is linked to whole grain-induced immunological improvements, ISME J source

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    • cites [138] Vuholm, 2017, Whole-grain rye and wheat affect some markers of gut health without altering the fecal microbiota in healthy overweight adults: a 6-week randomized trial, J Nutr

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    • cites [139] Roager, 2019, Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial, Gut source

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  • May combine two claims.

    Interpretationreasoning

    Given metagenomic enrichment of choline-metabolizing pathways in colorectal cancer patients, these findings support benefits of physical activity in reducing trimethylamine N-oxide production and colorectal cancer risk.

    “Give the finding of metagenomic enrichment of choline-metabolizing pathways in patients with CRC, 16 these findings support the benefits of physical activity in reducing production of TMAO and risk of CRC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Thomas, 2019, Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation, Nat Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The European Prospective Investigation into Cancer and Nutrition cohort consistently found an association between fiber intake and reduced colorectal cancer risk, in contrast to most US studies.

    “In contrast to most US studies, which reported no association,116–119 the European Prospective Investigation into Cancer and Nutrition cohort consistently found an association between fiber intake and reduced risk CRC.120–122”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [116] Kunzmann, 2015, Dietary fiber intake and risk of colorectal cancer and incident and recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Am J Clin Nutr source

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    • cites [117] Higginbotham, 2004, Dietary glycemic load and risk of colorectal cancer in the Women’s Health Study, J Natl Cancer Inst source

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    • cites [118] Michels, 2005, Fiber intake and incidence of colorectal cancer among 76,947 women and 47,279 men, Cancer Epidemiol Biomarkers Prev source

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    • cites [119] He, 2019, Dietary intake of fiber, whole grains and risk of colorectal cancer: an updated analysis according to food sources, tumor location and molecular subtypes in two large US cohorts, Int J Cancer source

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    • cites [120] Bingham, 2003, Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study, Lancet source

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    • cites [121] Bingham, 2005, Is the association with fiber from foods in colorectal cancer confounded by folate intake?, Cancer Epidemiol Biomarkers Prev source

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    • cites [122] Murphy, 2012, Dietary fibre intake and risks of cancers of the colon and rectum in the European Prospective Investigation into Cancer and Nutrition (EPIC), PloS One source

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    Premisecitation

    Eight weeks of mixed aerobic and resistance exercise training improved cardiorespiratory fitness and body composition but did not produce significant changes in the fecal microbiome or metabolites.

    “In the second study, 8 weeks of mixed aerobic and resistance exercise training improved cardiorespiratory fitness and body composition, but did not produce significant changes in the fecal microbiome114 or metabolites.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [114] Cronin, 2018, A prospective metagenomic and metabolomic analysis of the impact of exercise and/or whey protein supplementation on the gut microbiome of sedentary adults, mSystems source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Consumption of whole-grain wheat increases the fecal concentration of ferulic acid and the serum concentration of dihydroferulic acid, a metabolite derived from ferulic acid by Lactobacillus and Bifidobacterium.

    “Consumption of whole-grain wheat increases the fecal concentration of ferulic acid (the most abundant phenolic compound in whole grains) and serum concentration of dihydroferulic acid (a metabolite derived from ferulic acid by Lactobacillus and Bifidobacterium).136”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [136] Vitaglione, 2015, Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber, Am J Clin Nutr source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Synergistic mechanisms might augment production of beneficial metabolites and account for the ability of whole grains to reduce colorectal cancer risk compared with other food sources of dietary fiber.

    “Given the shared microbes in the synthesis of SCFA and dihydroferulic acid, synergistic mechanisms might augment the production of beneficial metabolites. These might account for ability of whole grains to reduce CRC risk compared with other food sources of dietary fiber.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Eating more fiber might lessen the cancer-promoting effects of Fusobacterium nucleatum by restoring immune surveillance.

    “It is possible that higher intake of fiber could reduce the carcinogenic effects of F nucleatum by restoring effective immunosurveillance.173”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [173] Mehta, 2018, Stability of the human faecal microbiome in a cohort of adult men, Nat Microbiol source

      Not checked in the free run.

    • Rests on an assumption: Fiber controls immune responses and Fusobacterium nucleatum levels.

  • May combine two claims.

    Premisecitation

    Serum glycochenodeoxycholic acid concentration was associated with colorectal cancer risk in women but not men in a large prospective serum metabolome study.

    “A large prospective study of serum metabolomes associated concentration of glycochenodeoxycholic acid with CRC risk in women but not in men.158”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [158] Cross, 2014, A prospective study of serum metabolites and colorectal cancer risk, Cancer source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Changes in bile acid composition and concentrations are associated with metabolic disorders and inflammatory bowel disease, which increase colorectal cancer risk.

    “Changes in bile acid composition and concentrations have been associated with metabolic disorders and IBD, which increases risk for CRC.161, 162”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [161] Staels, 2009, Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration, Diabetes Care source

      Not checked in the free run.

    • cites [162] Franzosa, 2019, Gut microbiome structure and metabolic activity in inflammatory bowel disease, Nat Microbiol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Several pathways are thought to connect the gut microbiota to colorectal cancer, including chronic inflammation, immune dysfunction, higher serum LPS, secondary bile acids, and leaky gut.

    “Chronic inflammation, dysfunction of immunity, increased serum levels of LPS, secondary bile acids, and leaky gut are representative pathways that link the gut microbiota with CRC (Figure 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Changes in trimethylamine N-oxide and choline were associated with increased insulin sensitivity in a weight-loss intervention study of obese individuals.

    “Changes in TMAO and choline associated with increased insulin sensitivity in a weight-loss intervention study of obese individuals.155”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [155] Heianza, 2019, Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial, Gut source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The ultimate effect of choline might depend on whether it is distributed in the circulation for one-carbon metabolism or in the gut for microbial trimethylamine N-oxide production.

    “so the ultimate effect of choline might depend on its distribution in the circulation for 1-carbon metabolism vs in the gut for microbial production of TMAO.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Song, 2015, Nutrients, foods, and colorectal cancer prevention, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A higher plasma level of trimethylamine N-oxide was associated with increased colorectal cancer risk, but this finding was not replicated.

    “A higher plasma level of TMAO was associated with an increased risk of CRC,151 but this finding was not replicated.152”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [151] Bae, 2014, Plasma choline metabolites and colorectal cancer risk in the Women’s Health Initiative Observational Study, Cancer Res source

      Not checked in the free run.

    • cites [152] Guertin, 2017, Serum trimethylamine N-oxide, carnitine, choline, and betaine in relation to colorectal cancer risk in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study, Cancer Epidemiol Biomarkers Prev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Butyrate raises vitamin D receptor mRNA and protein in the intestine, lessens dysbiosis, and triggers Paneth cell autophagy, which suppresses chronic inflammation.

    “Butyrate increases intestinal expression of vitamin D receptor mRNA and protein, reduces intestinal dysbiosis, and activates the autophagy response of Paneth cells to inhibit chronic inflammation.172”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [172] Wu, 2015, Intestinal epithelial vitamin D receptor deletion leads to defective autophagy in colitis, Gut source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Higher levels of choline and trimethylamine N-oxide have been linked to metabolic disturbances that might increase colorectal cancer risk, including higher body mass index, greater visceral adiposity, insulin resistance, diabetes, and fatty liver.

    “Higher levels of choline and TMAO have been linked to a spectrum of metabolic disturbances that might increase CRC risk, including higher BMI, greater visceral adiposity, insulin resistance, diabetes, and fatty liver.153, 154”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [153] Randrianarisoa, 2016, Relationship of serum trimethylamine N-oxide (TMAO) levels with early atherosclerosis in humans, Sci Rep source

      Not checked in the free run.

    • cites [154] Barrea, 2018, Trimethylamine-N-oxide (TMAO) as novel potential biomarker of early predictors of metabolic syndrome, Nutrients source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Compared with Caucasians, African Americans show much greater amounts of sulfur-reducing bacteria and B. wadsworthia, and this difference persists after diet is accounted for.

    “Interestingly, African Americans have substantially higher abundances of sulfur-reducing bacteria and B wadsworthia than Caucasians, even after adjusting for dietary variables.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [166] Yazici, 2017, Race-dependent association of sulfidogenic bacteria with colorectal cancer, Gut source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Gut hydrogen sulfide is produced either by sulfur-reducing bacteria from inorganic sulfur (sulfate and sulfite) used as a preservative in processed meat or by fermentative bacteria metabolizing organic sulfur compounds enriched in animal products such as red meat.

    “Hydrogen sulfide (H2S) is generated in the gut either by sulfur-reducing bacteria from inorganic sulfur (sulfate and sulfite) that is routinely used as a preservative in processed meat or by fermentative bacteria that metabolize organic sulfur compounds that are enriched in animal products such as red meat.3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Song, 2015, Nutrients, foods, and colorectal cancer prevention, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Diets linked to more sulfur-producing bacteria in stool were tied to a higher risk of cancer in the distal colon, but not the proximal colon.

    “we associated dietary patterns with higher fecal abundances of sulfur-producing and increased risk of distal CRC, but not proximal colon cancer.167”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] Nguyen LH, Abu-Ali G, Mehta RS, et al. Dietary patterns, sulfur intake, and the abundance of sulfate-reducing bacteria. Paper presented at: Digestive Disease Week; May 18-21, 2019; San Diego, CA.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    More short-chain fatty acids in stool correlate with more memory T cells in blood, lower inflammatory cytokines like tumor necrosis factor, and higher anti-inflammatory cytokines like interleukin 10.

    “Higher levels of fecal SCFAs were associated with increased numbers of memory T cells in blood,171 reduced levels of inflammatory cytokines (such as tumor necrosis factor), and increased levels of anti-inflammatory cytokines (such as interleukin 10).136”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [171] Vanegas, 2017, Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults, Am J Clin Nutr source

      Not checked in the free run.

    • cites [136] Vitaglione, 2015, Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber, Am J Clin Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An analysis of eight diverse fecal shotgun metagenomic studies found evidence of increased secondary bile acid production in colorectal cancer patients, suggesting that cancer-associated microbes are metabolically linked to a diet rich in fat and meat.

    “A recent analysis of 8 geographically and technically diverse fecal shotgun metagenomic studies found evidence for increased production of secondary bile acids in patients with CRC, indicating a metabolic link between cancer-associated microbes and a fat- and meat-rich diet. 146”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [146] Wirbel, 2019, Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer, Nat Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Obesity could drive colorectal carcinogenesis by causing systemic inflammation through LPS and by reducing short-chain fatty acid-producing bacteria.

    “For example, obesity might promote colorectal carcinogenesis via LPS-mediated systemic inflammation and depletion of SCFA-producing bacteria.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The carcinogenic effect of red and processed meat might be mediated by preservatives such as nitrates and nitrites, additives such as emulsifiers, chemicals produced during processing and cooking such as heterocyclic amines and polycyclic aromatic hydrocarbons, or nutrients enriched in meats such as heme iron, sulfur, and choline.

    “The carcinogenic effect might be mediated by preservatives in red and processed (such as nitrates and nitrites), other additives (such as emulsifiers), chemicals produced during meat processing and cooking (such as heterocyclic amines and polycyclic aromatic hydrocarbons), or nutrients enriched in meats (such as heme iron, sulfur, and choline).3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Song, 2015, Nutrients, foods, and colorectal cancer prevention, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Both genetic variants and environmental exposures add to dysbiosis and colorectal cancer development.

    “Genetic variants, along with environmental factors, also contribute to contribute to dysbiosis and development of CRC.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Akkermansia muciniphila and Faecalibacterium correlate with better anti-PDCD1 efficacy, perhaps by drawing more T cells into tumors and enhancing their activity.

    “A muciniphila195 and Faecalibacterium196 have been associated with greater efficacy of PDCD1 blocking agents—possibly by increasing recruitment of T cells to tumors and their functions there.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [195] Routy, 2018, Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors, Science source

      Not checked in the free run.

    • cites [196] Gopalakrishnan, 2018, Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients, Science source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Fecal microbiome changes seen in colorectal cancer patients also appear in adenoma patients, suggesting a possible screening use for people at risk.

    “Alterations in the fecal microbiomes of patients with CRC have also been observed in patients with colorectal adenoma—these might be used in screening for individuals at risk for CRC.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Most colorectal cancer screening methods have poor ability to detect proximal lesions.

  • May combine two claims.

    Premisecitation

    In mice, Citrobacter rodentium-induced colonic crypt hyperplasia comes with changes in beta-catenin and Notch signaling, barrier function, and fecal dysbiosis, and leads to colon tumors.

    “Mice with Citrobacter rodentium-induced colonic crypt hyperplasia have alterations in beta-catenin and Notch signaling, intestinal barrier function, and fecal dysbiosis, resulting in development of colon tumors.182, 183”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [182] Ahmed, 2012, Critical roles of Notch and Wnt/β-catenin pathways in the regulation of hyperplasia and/or colitis in response to bacterial infection, Infect Immun source

      Not checked in the free run.

    • cites [183] Ahmed, 2018, Enteric infection coupled with chronic Notch pathway inhibition alters colonic mucus composition leading to dysbiosis, barrier disruption and colitis, PLoS One source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Movement of microbial products and metabolites, higher serum LPS, and immune activation all drive dysbiosis, barrier failure, and inflammation.

    “Translocation of microbial products, metabolites, increased serum LPS, and immune activation promote dysbiosis, barrier failure, and inflammation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Bioinformatic and functional work suggests Fusobacterium nucleatum triggers innate immunity through TLR4 and MYD88, causing loss of certain microRNAs, which turns on autophagy and drives chemoresistance in colorectal cancer patients.

    “Bioinformatic and functional studies indicated that F nucleatum activates innate immune responses, via TLR4 and MYD88, resulting in loss of specific microRNAs. This resulted in activation of autophagy activation and promotion of chemoresistance in patients with CRC.28”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Yu, 2017, Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy, Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Stool microbiome testing detects adenomas with moderate accuracy, with validation AUCs between 0.55 and 0.67, which is below its accuracy for colorectal cancer.

    “Fecal microbiome analysis identifies patients with adenomas with reasonable levels of accuracy (area under receiver operating curves ranging from 0.55 to 0.67 in validation studies), although this is a lower value than for detection of CRC.16, 18, 186–188”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [16] Thomas, 2019, Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation, Nat Med source

      Not checked in the free run.

    • cites [18] Feng, 2015, Gut microbiome development along the colorectal adenoma-carcinoma sequence, Nat Commun source

      Not checked in the free run.

    • cites [186] Wong, 2017, Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia, Gut source

      Not checked in the free run.

    • cites [187] Baxter, 2016, Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions, Genome Med source

      Not checked in the free run.

    • cites [188] Dadkhah, 2019, Gut microbiome identifies risk for colorectal polyps, BMJ Open Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Multiple studies suggest gut microbiota can shape immunotherapy efficacy, but no evidence yet links it to immunotherapy for colorectal cancer.

    “Several studies have indicated that the gut microbiota can determine the efficacy of cancer immunotherapy, although there is no evidence for its effects on immunotherapy for CRC.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Fusobacterium nucleatum raises microRNA 21 in colorectal cancer cells through TLR4 signaling involving MYD88 and nuclear factor-kappa B, which boosts their proliferation.

    “F nucleatum induce expression of microRNA 21 by CRC cells by activating TLR4 signaling via MYD88 and nuclear factor-kappa B. This increased proliferation of the CRC cells.184”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [184] Yang, 2017, Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating Toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of microRNA-21, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This Bilophila wadsworthia increase came from a milk-fat diet shifting liver bile acid conjugation from glycocholic to taurocholic acid, which aids solubilization of the more hydrophobic milk-fat diet.

    “The Bilophila wadsworthia expansion resulted from a MF diet-induced shift in hepatic conjugation of bile acids, from glycocholic to taurocholic acid, which helps solubilize the more hydrophobic MF diet.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [174] Devkota, 2012, Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice, Nature source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Certain bacterial strains seem to disturb the gut microbiome and drive inflammation, raising the risk of inflammatory bowel disease and colon carcinogenesis.

    “Specific strains of bacteria therefore appear to disrupt the intestinal microbiome and promote inflammation to increase risk for IBD and colon carcinogenesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Measuring fecal Fusobacterium nucleatum alongside FIT doubled sensitivity for advanced adenomas, and an independent validation cohort showed a similar gain.

    “For example, addition of fecal F nucleatum quantitation to fecal immunochemical test, which has suboptimal sensitivity in detecting adenomas, doubled the sensitivity for detection of advanced adenomas. A similar improvement was observed in an independent validation cohort.186”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [186] Wong, 2017, Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia, Gut source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Changes in gut microbiota can change how well CpG-oligonucleotide immunotherapy and oxaliplatin work; antibiotic-treated or germ-free mice responded less to both.

    “Both therapies had reduced efficacy in mice given antibiotics or germ-free mice, which had lower production of cytokines and less tumor necrosis after CpG-oligonucleotide administration and reduced production of reactive oxygen species and cytotoxicity after chemotherapy compared.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [190] Iida, 2013, Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment, Science source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In colorectal cancer patients, greater consumption of fiber, marine omega-3s, vitamin D, calcium, coffee, or a plant-based low-carbohydrate diet has been linked to longer survival.

    “Higher intake of nutrients such as fiber,199 marine omega-3 fatty acid,200–202 vitamin D,203–205 or calcium,203 or coffee206, 207 or a plant-based low-carbohydrate diet207 has been associated with increased survival times of patients with CRC.”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [199] Song, 2018, Fiber intake and survival after colorectal cancer diagnosis, JAMA Oncol source

      Not checked in the free run.

    • cites [200] Cockbain, 2012, Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer, Gut source

      Not checked in the free run.

    • cites [201] Song, 2017, Marine omega-3 polyunsaturated fatty acid intake and survival after colorectal cancer diagnosis, Gut source

      Not checked in the free run.

    • cites [202] Van Blarigan, 2018, Dietary fat intake after colon cancer diagnosis in relation to cancer recurrence and survival: CALGB 89803 (Alliance), Cancer Epidemiol Biomarkers Prev source

      Not checked in the free run.

    • cites [203] Yang, 2019, Calcium intake and survival after colorectal cancer diagnosis, Clin Cancer Res source

      Not checked in the free run.

    • cites [204] Zgaga, 2014, Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer, J Clin Oncol source

      Not checked in the free run.

    • cites [205] Vaughan-Shaw, 2020, Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response, Gut source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Each year in the US, over a million people get Salmonella from food, mostly eggs, meats, dairy, and other contaminated non-animal foods.

    “More than 1 million people in the US acquire Salmonella infection annually as a foodborne illness mainly from eggs, meats, dairy, and other contaminated non-animal foods.178”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [178] Crum Cianflone, 2008, Salmonellosis and the GI tract: more than just peanut butter, Curr Gastroenterol Rep source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    Those C. elegans studies did not include colorectal cancer patients or mouse models.

    “However, no patients or mouse models of CRC were used in these studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The gut microbiota influences how cancer therapy works and how likely toxic side effects are, but human evidence remains limited.

    “In addition to affecting CRC development, the gut microbiota modulates the response to cancer therapy and susceptibility to toxic side effects, although there is only limited evidence from patients (for reviews, see 8, 189).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] Roy, 2017, Microbiota: a key orchestrator of cancer therapy, Nat Rev Cancer source

      Not checked in the free run.

    • cites [189] Alexander, 2017, Gut microbiota modulation of chemotherapy efficacy and toxicity, Nat Rev Gastroenterol Hepatol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Because many of these factors affect immunity and the microbiota, they could improve the effectiveness and lower the side effects of immunotherapies or other treatments.

    “Many of these factors have immunomodulatory and microbiota-modifying effects, so they might increase the efficacy and reduce the adverse effects of immunotherapies or other therapeutic agents.208”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [208] Song, 2018, The potential role of exercise and nutrition in harnessing the immune system to improve colorectal cancer survival, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Certain bacteria correlate with protection from immune checkpoint inhibitor-associated colitis, and fecal microbiota transplantation could be a treatment for it.

    “Moreover, specific bacteria have been associated with resistance to the development of immune checkpoint inhibitor-associated colitis,197 and fecal microbiota transplants might be used to treat this form of colitis.198”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [197] Dubin, 2016, Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis, Nat Commun source

      Not checked in the free run.

    • cites [198] Wang, 2018, Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis, Nat Med source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    Clinical studies have often been small, mostly under 100 cases, and probably lacked power to detect predictive signals among the many sequencing read counts.

    “Moreover, clinical studies have been limited by small sample sizes (mostly <100 cases), likely underpowered to identify predictive signals from hundreds to thousands of reads counts generated by high-throughput sequencing.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Whether the microbial changes found in colorectal carcinogenesis are causal or consequential remains unresolved.

    “It is not clear whether the identified microbial alterations are a cause or consequence of colorectal carcinogenesis.209”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [209] Tjalsma, 2012, A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects, Nat Rev Microbiol source

      Not checked in the free run.

72 of 72

  • The paper relies on this without support.

    Colorectal cancer-related risk factors are associated with specific changes in the intestinal microbiota, even though there is no direct evidence for this.

    “Although there is no direct evidence, CRC-related risk factors have been associated with specific changes in the intestinal microbiota.”

  • The paper relies on this without support.

    The composition of the microbiota is determined by genetic, environmental, and dietary factors.

    “The composition of microbiota is determined by genetic, environmental, and dietary factors.”

  • The paper relies on this without support.

    Fiber controls immune responses and Fusobacterium nucleatum levels.

    “Fiber regulates the immune response and levels of F nucleatum.”

  • The paper relies on this without support.

    Short-chain fatty acid-producing bacteria such as Roseburia and Lachnospira lower colorectal cancer risk.

    “SCFA-producing bacteria, such as Roseburia and Lachnospira, reduce risk of CRC.”

  • The paper relies on this without support.

    Most colorectal cancer screening methods have poor ability to detect proximal lesions.

    “Most screening methods have limited abilities to detect proximal lesions (such as the fecal immunohistochemical test, flexible sigmoidoscopy, and colonoscopy), so it is important to determine whether analyses of fecal microbiomes can improve the sensitivity of detection of proximal colon neoplasias.”

  • The paper relies on this without support.

    The intestine must maintain commensal microbes and a high load of bacterial products while responding quickly to pathogens.

    “The intestine must maintain commensal microbes and a high load of bacterial products, but swiftly respond to pathogens that threaten its integrity.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Lack of a "healthy" microbiota is associated with many forms of disease, including metabolic diseases, gastrointestinal cancer, inflammatory bowel disease, renal disease, and neurodegenerative diseases associated with aging.

    “Lack of a “healthy” microbiota is associated with many forms of disease (19–24), such as metabolic diseases (obesity, type 2 diabetes), gastrointestinal cancer, inflammatory bowel disease, and renal disease, as well as neurodegenerative diseases (NDs) associated with aging, in which the activity and composition of the gut microbiota change during the life cycle.”

    From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [23]

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Martin, 2004, Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer, Gastroenterology, 127, 80, 10.1053/j.gastro.2004.03.054 · DOI
  2. Roager, 2019, Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial, Gut, 68, 83, 10.1136/gutjnl-2017-314786 · DOI
  3. Staels, 2009, Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration, Diabetes Care, 32, S237, 10.2337/dc09-S355 · DOI
  4. Yazici, 2015, Bilophila wadsworthia is more abundant in the colonic microbiome of colorectal cancer cases compared to healthy controls, Gastroenterology, 148
  5. Yu, 2017, Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer, Gut, 66, 70, 10.1136/gutjnl-2015-309800 · DOI

Cited by

Sorted by citations

Authors
Song, M., Chan, A. T., & Sun, J.
Affiliations
  • Harvard University (US)
  • Broad Institute (US)
  • University of Illinois Chicago (US)
Corresponding author
  • Chan, Andrew T.
  • Sun, Jun
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2020-01
Volume
158
Issue
2
Pages
322-340
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2019.06.048
PMC
PMC6957737
OpenAlex
W2978077164
Cited by
752
References
217
Citations by year
2026: 66 · 2025: 124 · 2024: 155 · 2023: 140 · 2022: 125 · 2021: 106 · 2020: 32 · 2019: 2 · 2018: 2
FWCI
5.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Gastroenterology (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (NIDDK R01 DK105118, R01DK114126)
  • U.S. Department of Defense
  • University of Illinois at Chicago
  • Cancer Center, University of Illinois at Chicago
  • American Cancer Society (K99 CA215314, MRSG-17-220-01 \u2013 NEC)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
Keywords
colorectal cancer, gut microbiota, diet, environmental factors, obesity, physical activity, dietary fiber, red and processed meat, whole grains, microbiota metabolites, cancer risk, chemoprevention, cancer screening, immune pathways, metabolic pathways
MeSH terms
Gastrointestinal Microbiome, Bacteria, Colon, Feeding Behavior, Humans, Intestinal Mucosa, Mass Screening, Risk Factors, Colorectal Neoplasms, Exercise, Incidence, Early Detection of Cancer

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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