Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer

Abstract

The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.

The Road to Infection: Host-Microbe Interactions Defining the Pathogenicity of Streptococcus bovis/Streptococcus equinus Complex Members

“…Additionally, 7% of non-advanced adenomas were double-positive to Pil1A-Pil1B, compared to 0% of controls ( p -value < 0.0001) (Butt et al, 2017 ). Data from a recent nested case-control study confirm previous observations that single marker panels are not sufficient to identify CRC patients and adenomas (Butt et al, 2017 , 2018 ). This is potentially due to significant heterogeneity in IgG response between patients and depends on the antigenicity of the strain triggering the immune response.…”

Colon Cancer with Streptococcus gallolyticus Aortic Valve Endocarditis: A Missing Link?

“…Follow-up of a colon cancer patient in Spain revealed that antibody response to pilus protein Gallo 2039, Gallo2178, and Gallo 2179 has been associated with an increased risk of colon cancer [13]. Antibody response to S. gallolyticus is mounted prior to emergence of malignancy in the colonic tissue [14].…”

The antibody/microbiota interface in health and disease

“…[88][89][90] A prospective study recently associated a commensal candidate, Streptococcus gallolyticus subspecies gallolyticus (SGG) with the risk to develop CRC, since anti-SGG IgG were more frequently present in individuals who developed cancer later in life (Table 2). 91 Although a causative link between the presence of such species and CRC has not been demonstrated, certain anti-commensal IgA 92 or IgG 91 reactivities might constitute potential diagnostic biomarkers for CRC. The detection of anti-commensal IgG might also offer novel opportunities for predicting immunotherapy efficacy in the treatment of cancers.…”