Abstract & Commentary

Streptococcus bovis Group Organisms and the Association with Colon Cancer: Pinning the Tail on the Donkey

By Brian G. Blackburn, MD, Clinical Assistant Professor of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine; is Associate Editor for Infectious Disease Alert.

Dr. Blackburn reports no financial relationship to this field of study.

Synopsis: Among Streptococcus bovis-infected patients who underwent gastrointestinal evaluation, 60% had colorectal adenomas or carcinomas, which appeared to be more common than in the general population. Those infected with S. bovis biotype 1 (Streptococcus gallolyticus) were 7.3 times more likely to have colorectal adenomas or carcinomas than those infected with other S. bovis biotypes.

Source: Boleij A, et al. Clinical importance of Streptococcus gallolyticus infection among colorectal cancer patients: Systematic review and meta-analysis. Clin Infect Dis 2011;53:870-878.

The association between S. bovis group infection (particularly endocarditis) and concurrent colorectal neoplasia has been known for some time.1,2 In recent years, better delineation of the different biotypes of the S. bovis complex has occurred, with a recent proposal to re-classify the complex based on molecular characteristics.3 Using this system, Streptococcus gallolyticus subsp. gallolyticus (formerly S. bovis biotype I), commonly referred to as S. gallolyticus, appears to be emerging as the pathogen most strongly associated with colorectal neoplasia; conversely, this association may be less strong for the other three S. bovis biotypes that are regarded principally as human pathogens (S. infantarius, S. lutiensis, and S. pasteurianus). Given the heterogeneity in the nomenclature of the organisms that comprise the S. bovis complex, and this possible differential association among biotypes with colorectal neoplasia, the authors undertook a meta-analysis to better delineate this association.

The meta-analysis predominantly consisted of 11 retrospective case series. Among S. bovis-infected patients who underwent evaluation of the gastrointestinal tract, 60% had colorectal adenomas or carcinomas; more than one-quarter of these were carcinomas. Although only one study in the meta-analysis reported colorectal neoplasia rates in age-matched controls, the colorectal neoplasia prevalence rates in this study were 56% in patients with S. bovis infections, and 27% in controls; however, the absolute numbers and a statistical comparative test were not reported.

In the subset of studies that determined S. bovis biotypes, patients infected with S. gallolyticus (biotype I) were significantly more likely than patients infected with other biotypes to have colorectal neoplasia (odds ratio [OR], 7.3; 95% confidence interval [CI], 3.9-13.4). S. gallolyticus (biotype I)-infected patients were also more likely to have endocarditis than patients infected with other biotypes (OR, 16.6; 95% CI, 8.9-31.2). Conversely, patients whose S. gallolyticus infection was endocarditis were more likely to have colorectal neoplasia than those patients whose infection was not endocarditis (OR, 3.7; 95% CI, 2.0-6.8).

Commentary

Although there are some limitations to this study (including the inconsistent naming of S. bovis biotypes in the studies included in the meta-analysis, the inconsistent screening of patients for colon cancer, and the retrospective nature of the studies), these data provide evidence that patients infected with S. gallolyticus have a high prevalence of colorectal neoplasia (both adenomas and carcinomas), probably above that of the general population. This association was particularly strong for those patients who had endocarditis caused by S. gallolyticus. This association was stronger than the associations seen with other S. bovis biotypes, for which the associations with colorectal neoplasia may not have been stronger than that of the general population.

The biologic mechanism underlying this association between S. gallolyticus infection and colorectal neoplasia may be the high affinity that this organism has for binding to collagen I/IV, which is overexpressed in colorectal polyps and cancers. This likely results in a higher carriage rate of this organism in the colon of patients with these lesions, and places them at higher risk for invasive infection with S. gallolyticus. Binding to type I collagen (which is present on heart valves) may also explain the affinity this organism has for causing infectious endocarditis.

Because many clinicians are not yet familiar with the new terminology involving these organisms, increasing awareness of this new nomenclature regarding different biotypes in the S. bovis complex is an important implication of this study, as is increasing awareness of the high risk S. gallolyticus-infected patients have of a concomitant colorectal neoplasm. Systematic screening of such patients with colonoscopy might lead to earlier diagnosis of such lesions. Microbiology laboratories should also consider attempting to identify S. bovis infections to the biotype level (using molecular methods) on a more routine basis, given the important clinical ramifications an S. gallolyticus infection has compared to other biotypes and the need for infected patients to undergo colonoscopy.

References

  1. McCoy W, et al. Enterococcal endocarditis associated with carcinoma of the sigmoid; report of a case. J Med Assoc State Ala 1951;21:162-166.
  2. Hoppes WL, et al. Nonenterococcal group-D streptococcal endocarditis caused by Streptococcus bovis. Ann Intern Med 1974;81:588-593.
  3. Schlegel L, et al. Reappraisal of the taxonomy of the Streptococcus bovis/Streptococcus equinus complex and related species: Description of Streptococcus gallolyticus subsp. gallolyticus subsp. nov., S. gallolyticus subsp. macedonicus subsp. nov. and S. gallolyticus subsp. pasteurianus subsp. nov. Int J Syst Evol Microbiol 2003;53:631-645.