Association Between Sulfur-Metabolizing Bacterial Communities in Stool and Risk of Distal Colorectal Cancer in Men.

BACKGROUND & AIMS Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H2S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men. METHODS We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study, since 1986, to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow up. First, in a subcohort of 307 healthy men, we profiled serial stool metagenomes and meta-transcriptomes and assessed diet using semi-quantitative food frequency questionnaires to identify food groups associated with 43 bacterial species involved in sulfur metabolism. We used these data to develop a sulfur microbial dietary score. We then used Cox proportional hazards modeling to evaluate adherence to this pattern among eligible individuals (n=48,246) from 1986 through 2012 with risk for incident CRC. RESULTS Foods associated with higher sulfur microbial diet scores included increased consumption of processed meats and low-calorie drinks and lower consumption of vegetables and legumes. Increased sulfur microbial diet scores were associated with risk of distal colon and rectal cancers, after adjusting for other risk factors (multivariable relative risk, highest vs lowest quartile, 1.43; 95% CI, 1.14-1.81; Ptrend=.002). In contrast, sulfur microbial diet scores were not associated with risk of proximal colon cancer (multivariable relative risk, 0.86; 95% CI, 0.65-1.14; Ptrend=.31]. CONCLUSIONS In an analysis of participants in the Health Professionals Follow-up Study, we found that long-term adherence to a dietary pattern associated with sulfur-metabolizing bacteria in stool was associated with an increased risk of distal CRC. Further studies are needed to determine how sulfur-metabolizing bacteria might contribute to CRC pathogenesis.

[1]  V. Leone,et al.  Regional Diversity of the Gastrointestinal Microbiome. , 2019, Cell host & microbe.

[2]  Tomoyoshi Soga,et al.  Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer , 2019, Nature Medicine.

[3]  P. Bork,et al.  Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation , 2019, Nature Medicine.

[4]  Paul Theodor Pyl,et al.  Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer , 2019, Nature Medicine.

[5]  M. Song,et al.  Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention. , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[6]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[7]  F. Bäckhed,et al.  Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration. , 2018, Cell host & microbe.

[8]  Curtis Huttenhower,et al.  bioBakery: a meta’omic analysis environment , 2017, Bioinform..

[9]  Markus Krummenacker,et al.  The MetaCyc database of metabolic pathways and enzymes , 2017, Nucleic acids research.

[10]  E. Rimm,et al.  Metatranscriptome of human fecal microbial communities in a cohort of adult men , 2018, Nature Microbiology.

[11]  E. Rimm,et al.  Stability of the human faecal microbiome in a cohort of adult men , 2018, Nature Microbiology.

[12]  Donna Neuberg,et al.  Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer , 2017, Science.

[13]  Arthur Brady,et al.  Strains, functions and dynamics in the expanded Human Microbiome Project , 2017, Nature.

[14]  David A. Drew,et al.  Dietary Patterns and Risk of Colorectal Cancer: Analysis by Tumor Location and Molecular Subtypes. , 2017, Gastroenterology.

[15]  N. Ellis,et al.  Race-dependent association of sulfidogenic bacteria with colorectal cancer , 2017, Gut.

[16]  Antje Chang,et al.  BRENDA in 2017: new perspectives and new tools in BRENDA , 2016, Nucleic Acids Res..

[17]  S. Ng,et al.  Understanding and Preventing the Global Increase of Inflammatory Bowel Disease. , 2017, Gastroenterology.

[18]  W. Garrett,et al.  Gut Microbiota, Inflammation, and Colorectal Cancer. , 2016, Annual review of microbiology.

[19]  W. Willett,et al.  Development and Validation of an Empirical Dietary Inflammatory Index. , 2016, The Journal of nutrition.

[20]  Amnon Amir,et al.  Preservation Methods Differ in Fecal Microbiome Stability, Affecting Suitability for Field Studies , 2016, mSystems.

[21]  R. van der Meer,et al.  Sulfide as a Mucus Barrier-Breaker in Inflammatory Bowel Disease? , 2016, Trends in molecular medicine.

[22]  Duy Tin Truong,et al.  MetaPhlAn2 for enhanced metagenomic taxonomic profiling , 2015, Nature Methods.

[23]  M. Kleerebezem,et al.  Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon , 2015, Proceedings of the National Academy of Sciences.

[24]  Herbert Tilg,et al.  Gut microbiome development along the colorectal adenoma-carcinoma sequence , 2015 .

[25]  A. Chan,et al.  Nutrients, foods, and colorectal cancer prevention. , 2015, Gastroenterology.

[26]  Jens Roat Kultima,et al.  Temporal and technical variability of human gut metagenomes , 2015, Genome Biology.

[27]  Qiang Feng,et al.  Gut microbiome development along the colorectal adenoma–carcinoma sequence , 2015, Nature Communications.

[28]  Peter B. McGarvey,et al.  UniRef clusters: a comprehensive and scalable alternative for improving sequence similarity searches , 2014, Bioinform..

[29]  Harry J. Flint,et al.  The gut microbiota, bacterial metabolites and colorectal cancer , 2014, Nature Reviews Microbiology.

[30]  H. Gaskins,et al.  Intestinal and systemic inflammatory responses are positively associated with sulfidogenic bacteria abundance in high-fat-fed male C57BL/6J mice. , 2014, The Journal of nutrition.

[31]  C. Huttenhower,et al.  Relating the metatranscriptome and metagenome of the human gut , 2014, Proceedings of the National Academy of Sciences.

[32]  N. Takahashi,et al.  Effects of pH and Lactate on Hydrogen Sulfide Production by Oral Veillonella spp , 2014, Applied and Environmental Microbiology.

[33]  M. Ebert,et al.  Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome , 2014, European Journal of Clinical Microbiology & Infectious Diseases.

[34]  Lawrence A. David,et al.  Diet rapidly and reproducibly alters the human gut microbiome , 2013, Nature.

[35]  W. Willett,et al.  A prospective study of long-term intake of dietary fiber and risk of Crohn's disease and ulcerative colitis. , 2013, Gastroenterology.

[36]  J. Gordon,et al.  Metabolic niche of a prominent sulfate-reducing human gut bacterium , 2013, Proceedings of the National Academy of Sciences.

[37]  S. Sarker.  Faculty Opinions recommendation of Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. , 2013 .

[38]  Brittany D. Needham,et al.  Modulating the innate immune response by combinatorial engineering of endotoxin , 2013, Proceedings of the National Academy of Sciences.

[39]  H. Gaskins,et al.  Microbial pathways in colonic sulfur metabolism and links with health and disease , 2012, Front. Physio..

[40]  R. Sinha,et al.  Socioeconomic status and the risk of colorectal cancer , 2012, Cancer.

[41]  C. Xiang,et al.  Human Intestinal Lumen and Mucosa-Associated Microbiota in Patients with Colorectal Cancer , 2012, PloS one.

[42]  S. O'keefe,et al.  Hydrogenotrophic microbiota distinguish native Africans from African and European Americans. , 2012, Environmental microbiology reports.

[43]  Bernard Henrissat,et al.  Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome , 2012, PLoS Comput. Biol..

[44]  K. Shaker,et al.  Myrosinase Hydrolysates of Brassica oleraceae L. Var. italica Reduce the Risk of Colon Cancer , 2012, Phytotherapy research : PTR.

[45]  Yunwei Wang,et al.  Dietary fat-induced taurocholic acid production promotes pathobiont and colitis in IL-10−/− mice , 2012, Nature.

[46]  Levi Waldron,et al.  Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum , 2012, Gut.

[47]  B. Peleteiro,et al.  Dietary patterns and colorectal cancer: systematic review and meta-analysis , 2012, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[48]  M. Kleerebezem,et al.  Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa , 2011, Nature Reviews Microbiology.

[49]  F. Bushman,et al.  Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes , 2011, Science.

[50]  A. Mellmann,et al.  Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. , 2011, The Lancet. Infectious diseases.

[51]  J. Clemente,et al.  Diet Drives Convergence in Gut Microbiome Functions Across Mammalian Phylogeny and Within Humans , 2011, Science.

[52]  J. Palmer,et al.  Dietary Patterns and the Risk of Colorectal Adenomas: the Black Women's Health Study , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[53]  H. El‐Serag,et al.  Dietary Intake and Risk of Developing Inflammatory Bowel Disease: A Systematic Review of the Literature , 2011, The American Journal of Gastroenterology.

[54]  E. Szigethy,et al.  Inflammatory bowel disease. , 2011, Pediatric clinics of North America.

[55]  D. Antonopoulos,et al.  Regional Mucosa-Associated Microbiota Determine Physiological Expression of TLR2 and TLR4 in Murine Colon , 2010, PloS one.

[56]  Ming-Jie Wang,et al.  Hydrogen sulfide induces human colon cancer cell proliferation: Role of Akt, ERK and p21 , 2010, Cell biology international.

[57]  R. Knight,et al.  The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice , 2009, Science Translational Medicine.

[58]  Rob Knight,et al.  High-fat diet determines the composition of the murine gut microbiome independently of obesity. , 2009, Gastroenterology.

[59]  F. Shanahan,et al.  Culture-independent analysis of desulfovibrios in the human distal colon of healthy, colorectal cancer and polypectomized individuals. , 2009, FEMS microbiology ecology.

[60]  A F Subar,et al.  Associations between food patterns defined by cluster analysis and colorectal cancer incidence in the NIH–AARP diet and health study , 2009, European Journal of Clinical Nutrition.

[61]  A. Velcich,et al.  The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria , 2008, Proceedings of the National Academy of Sciences.

[62]  L. Fulton,et al.  Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. , 2008, Cell host & microbe.

[63]  G. Combs,et al.  Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. , 2008, The Journal of nutritional biochemistry.

[64]  G. Ning,et al.  Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. , 2008, American journal of physiology. Gastrointestinal and liver physiology.

[65]  B. Necela,et al.  Differential expression, distribution, and function of PPAR-γ in the proximal and distal colon , 2007 .

[66]  M. Attene-Ramos,et al.  Hydrogen Sulfide Induces Direct Radical-Associated DNA Damage , 2007, Molecular Cancer Research.

[67]  B. Necela,et al.  Differential expression, distribution, and function of PPAR-gamma in the proximal and distal colon. , 2007, Physiological genomics.

[68]  F. Clavel-Chapelon,et al.  Dietary patterns and risk of colorectal tumors: a cohort of French women of the National Education System (E3N). , 2006, American journal of epidemiology.

[69]  P. Laird,et al.  Smad3 deficiency promotes tumorigenesis in the distal colon of ApcMin/+ mice. , 2006, Cancer research.

[70]  P. Tanière,et al.  Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[71]  Dae-Joong Kang,et al.  Bile salt biotransformations by human intestinal bacteria Published, JLR Papers in Press, November 18, 2005. , 2006, Journal of Lipid Research.

[72]  H. Vainio,et al.  Isothiocyanates in Cancer Prevention , 2004, Drug metabolism reviews.

[73]  W. Willett,et al.  Major dietary patterns and the risk of colorectal cancer in women. , 2003, Archives of internal medicine.

[74]  Kan Yang,et al.  Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2 , 2002, Science.

[75]  Peter D. Karp.  The MetaCyc Metabolic Pathway Database , 2002 .

[76]  F B Hu,et al.  Prospective study of major dietary patterns and colorectal cancer risk in women. , 2001, American journal of epidemiology.

[77]  R. Hughes,et al.  Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans. , 2000, The American journal of clinical nutrition.

[78]  J. Kaprio,et al.  Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. , 2000, The New England journal of medicine.

[79]  S. Lewis,et al.  Stool form scale as a useful guide to intestinal transit time. , 1997, Scandinavian journal of gastroenterology.

[80]  G A Colditz,et al.  Reproducibility and validity of a self-administered physical activity questionnaire. , 1994, International journal of epidemiology.

[81]  W. Roediger,et al.  Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. , 1993, Gastroenterology.

[82]  G A Colditz,et al.  Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. , 1992, American journal of epidemiology.

[83]  G. Macfarlane,et al.  Comparison of fermentation reactions in different regions of the human colon. , 1992, The Journal of applied bacteriology.

[84]  H. Werner,et al.  [A new butyric acid-producing bacteroides species: B. splanchnicus n. sp. (author's transl)]. , 1975, Zentralblatt fur Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene. Erste Abteilung Originale. Reihe A: Medizinische Mikrobiologie und Parasitologie.