Advertisement

The Sulfur Microbial Diet and Micro-managing Early-Onset Colorectal Neoplasia

  • Wade Billings
    Correspondence
    Correspondence Address correspondence to: Wade Billings, MD, Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Rotary Building, Suite 225, Indianapolis, IN 46202.
    Affiliations
    Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
    Search for articles by this author
  • Anna Krigel
    Correspondence
    Anna Krigel, MD, MS, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032.
    Affiliations
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York
    Search for articles by this author
      See “The sulfur microbial diet is associated with increased risk of early-onset colorectal cancer precursors,” by Nguyen LH, Cao Y, Hur J, et al, on page 1423.
      The incidence of colorectal cancer (CRC) and its associated mortality has increased in recent years in adults younger than 50 years of age.
      • Siegel R.L.
      • Fedewa S.A.
      • Anderson W.F.
      • et al.
      Colorectal cancer incidence patterns in the United States, 1974–2013.
      ,
      • Siegel R.L.
      • Jemal A.
      • Ward E.M.
      Increase in incidence of colorectal cancer among young men and women in the United States.
      Multiple societies have updated their CRC screening guidelines to reflect this rise, now recommending that CRC screening begin for all average-risk individuals starting at age 45 instead of age 50.
      • Davidson K.W.
      • Barry M.J.
      • et al.
      US Preventive Services Task Force
      Screening for colorectal cancer: US Preventive Services Task Force recommendation statement.
      ,
      • Wolf A.M.D.
      • Fontham E.T.H.
      • Church T.R.
      • et al.
      Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.
      While this worrisome phenomenon and the subsequent guidelines changes it has prompted have been the topic of much recent research and have even been widely covered in the lay media,
      • Krigel A.
      • Prasad V.K.
      • Lebwohl B.
      News coverage of the american cancer society’s update to colorectal cancer screening guidelines.
      early-onset CRC remains largely unexplained. Given the observed birth cohort effect in CRC incidence,
      • Siegel R.L.
      • Miller K.D.
      • Goding Sauer A.
      • et al.
      Colorectal cancer statistics, 2020.
      much attention has been paid to possible associated lifestyle and dietary risk factors.
      This issue of Gastroenterology features a study that adds an important piece to the early-onset CRC puzzle. Nguyen et al
      • Nguyen L.H.
      • Cao Y.
      • Hur J.
      • et al.
      The sulfur microbial diet is associated with increased risk of early-onset colorectal cancer precursors.
      examine the association between consumption of the sulfur microbial diet (a diet with high intake of processed meats and low intake of mixed vegetables and legumes) with increased risk of early-onset colorectal neoplasia (colorectal adenoma or serrated polyp) in women participating in the Nurses’ Health Study II. A diet high in foods with a positive association with the enrichment of sulfur-metabolizing bacteria may in turn increase the microbial production of hydrogen sulfide (H2S), which is known to be pro-carcinogenic. This group previously showed an association between the sulfur microbial diet and risk for colorectal cancer in a cohort of older men.
      • Nguyen L.H.
      • Ma W.
      • Wang D.D.
      • et al.
      Association between sulfur-metabolizing bacterial communities in stool and risk of distal colorectal cancer in men.
      In this study in a large cohort of younger women, the authors found that those in the highest quartile of sulfur microbial diet scores had increased risk of early-onset conventional adenomas on colonoscopy, although there was no association with early-onset serrated lesions. Moreover, the sulfur microbial diet was even more strongly associated with finding an adenoma with advanced histology, such as tubulovillous or villous adenomas, which carry greater malignant potential. When high intake of foods associated with the sulfur microbial diet in adolescence was separately assessed, the positive association with early-onset conventional adenomas persisted, albeit with smaller odds ratios (ORs). While the OR for the overall association with conventional adenomas was significant but modest at 1.31, the association with early-onset advanced adenomas was even stronger (OR 1.65). As such, these findings may help to explain, at least in part, the rising rates of early-onset CRC.
      This large prospective longitudinal cohort study using a validated food frequency questionnaire is similar in design as others using the same cohort,
      • Liu P.H.
      • Wu K.
      • Ng K.
      • et al.
      Association of obesity with risk of early-onset colorectal cancer among women.
      and such robust data are hard to come by in dietary studies. The population is entirely female, which may limit generalizability, but does provide meaningful insight into colorectal carcinogenesis specific to women and early-onset adenomas. Food frequency data from adolescence is included and found to be similar to reported diet through adulthood, but these data are subject to recall bias given the considerable time between the survey and the adolescent years. As with any observational study, there is potential for unmeasured confounding variables, although the authors control for a number of relevant variables in their analysis. In addition, other studies from the same cohort have used CRC as the primary end point instead of the surrogate end point of any colorectal neoplasia as was used in this study, which could affect the already modest effect size.
      • Liu P.H.
      • Wu K.
      • Ng K.
      • et al.
      Association of obesity with risk of early-onset colorectal cancer among women.
      There have been an increasing number of studies, including several using the same cohort, that have identified various lifestyle aspects as risk factors for early-onset adenoma or CRC, including obesity,
      • Liu P.H.
      • Wu K.
      • Ng K.
      • et al.
      Association of obesity with risk of early-onset colorectal cancer among women.
      ,
      • Kim N.H.
      • Jung Y.S.
      • Yang H.J.
      • et al.
      Prevalence of and risk factors for colorectal neoplasia in asymptomatic young adults (20–39 years old).
      alcohol,
      • Kim N.H.
      • Jung Y.S.
      • Yang H.J.
      • et al.
      Prevalence of and risk factors for colorectal neoplasia in asymptomatic young adults (20–39 years old).
      ,
      • Rosato V.
      • Bosetti C.
      • Levi F.
      • et al.
      Risk factors for young-onset colorectal cancer.
      Western diet,
      • Khan N.A.
      • Hussain M.
      • ur Rahman A.
      • et al.
      Dietary practices, addictive behavior and bowel habits and risk of early onset colorectal cancer: a case control study.
      ,
      • Nimptsch K.
      • Wu K.
      Is timing important? The role of diet and lifestyle during early life on colorectal neoplasia.
      , red and processed meat,
      • Aykan N.F.
      Red meat and colorectal cancer.
      ,
      • Vargas A.J.
      • Thompson P.A.
      Diet and nutrient factors in colorectal cancer risk.
      and the sulfur microbial diet.
      • Nguyen L.H.
      • Ma W.
      • Wang D.D.
      • et al.
      Association between sulfur-metabolizing bacterial communities in stool and risk of distal colorectal cancer in men.
      This study adds to the existing body of evidence that diet may be associated with early-onset colorectal neoplasia. This study not only demonstrates a link between a diet with a high sulfur microbial score and an increased risk of earlier-onset, higher-risk adenomas, but also begins to provide a mechanistic link connecting the two. Interestingly, this study found higher rates of proximal and earlier-onset adenomas in younger women, in contrast to the distal CRC risk found in older men with higher sulfur microbial diet scores.
      • Nguyen L.H.
      • Ma W.
      • Wang D.D.
      • et al.
      Association between sulfur-metabolizing bacterial communities in stool and risk of distal colorectal cancer in men.
      The authors found no link between the sulfur-microbial diet and adenomas in women over 50 years of age. These important differences add to the understanding of the complex relationship of host-microbiome and of colorectal carcinogenesis along different anatomic sites.
      • Yamauchi M.
      • Morikawa T.
      • Kuchiba A.
      • et al.
      Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum.
      The sulfur-microbial diet and its components, including processed meats, sugar-sweetened beverages, and low intake of vegetables and legumes, has concerning links to numerous negative health outcomes.
      • Soliman G.A.
      Dietary fiber, atherosclerosis, and cardiovascular disease.
      ,
      • Wolk A.
      Potential health hazards of eating red meat.
      A basic understanding of the connection between these dietary factors and early-onset CRC may be nearing the horizon, and these findings provide meaningful insight into an underlying mechanism through host-diet-microbiome relationships. Future research should further investigate the pathophysiologic link between these diets and colorectal carcinogenesis as well as how manipulation of the gut microbiome and/or its downstream effects may mitigate these risks. Counseling patients on healthy diet choices, particularly early in life, has long been common-sense practice, and now clinicians have more supporting evidence on specific dietary factors and risk of CRC to bring to the conversation.

      References

        • Siegel R.L.
        • Fedewa S.A.
        • Anderson W.F.
        • et al.
        Colorectal cancer incidence patterns in the United States, 1974–2013.
        J Natl Cancer Inst. 2017; 109: djw322
        • Siegel R.L.
        • Jemal A.
        • Ward E.M.
        Increase in incidence of colorectal cancer among young men and women in the United States.
        Cancer Epidemiol Biomarkers Prev. 2009; 18: 1695-1698
        • Davidson K.W.
        • Barry M.J.
        • et al.
        • US Preventive Services Task Force
        Screening for colorectal cancer: US Preventive Services Task Force recommendation statement.
        JAMA. 2021; 325: 1965-1977
        • Wolf A.M.D.
        • Fontham E.T.H.
        • Church T.R.
        • et al.
        Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.
        CA Cancer J Clin. 2018; 68: 250-281
        • Krigel A.
        • Prasad V.K.
        • Lebwohl B.
        News coverage of the american cancer society’s update to colorectal cancer screening guidelines.
        Mayo Clin Proc. 2020; 95: 617-618
        • Siegel R.L.
        • Miller K.D.
        • Goding Sauer A.
        • et al.
        Colorectal cancer statistics, 2020.
        CA Cancer J Clin. 2020; 70: 145-164
        • Nguyen L.H.
        • Cao Y.
        • Hur J.
        • et al.
        The sulfur microbial diet is associated with increased risk of early-onset colorectal cancer precursors.
        Gastroenterology. 2021; 161: 1423-1432
        • Nguyen L.H.
        • Ma W.
        • Wang D.D.
        • et al.
        Association between sulfur-metabolizing bacterial communities in stool and risk of distal colorectal cancer in men.
        Gastroenterology. 2020; 158: 1313-1325
        • Liu P.H.
        • Wu K.
        • Ng K.
        • et al.
        Association of obesity with risk of early-onset colorectal cancer among women.
        JAMA Oncol. 2019; 5: 37-44
        • Kim N.H.
        • Jung Y.S.
        • Yang H.J.
        • et al.
        Prevalence of and risk factors for colorectal neoplasia in asymptomatic young adults (20–39 years old).
        Clin Gastroenterol Hepatol. 2019; 17: 115-122
        • Rosato V.
        • Bosetti C.
        • Levi F.
        • et al.
        Risk factors for young-onset colorectal cancer.
        Cancer Causes Control. 2013; 24: 335-341
        • Khan N.A.
        • Hussain M.
        • ur Rahman A.
        • et al.
        Dietary practices, addictive behavior and bowel habits and risk of early onset colorectal cancer: a case control study.
        Asian Pac J Cancer Prev. 2015; 16: 7967-7973
        • Nimptsch K.
        • Wu K.
        Is timing important? The role of diet and lifestyle during early life on colorectal neoplasia.
        Curr Colorectal Cancer Rep. 2018; 14: 1-11
        • Aykan N.F.
        Red meat and colorectal cancer.
        Oncol Rev. 2015; 9: 288
        • Vargas A.J.
        • Thompson P.A.
        Diet and nutrient factors in colorectal cancer risk.
        Nutr Clin Pract. 2012; 27: 613-623
        • Yamauchi M.
        • Morikawa T.
        • Kuchiba A.
        • et al.
        Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum.
        Gut. 2012; 61: 847-854
        • Soliman G.A.
        Dietary fiber, atherosclerosis, and cardiovascular disease.
        Nutrients. 2019; 11
        • Wolk A.
        Potential health hazards of eating red meat.
        J Intern Med. 2017; 281: 106-122

      Linked Article