Digestive Diseases and Sciences ( IF 2.5 ) Pub Date : 2023-06-20 , DOI: 10.1007/s10620-023-08001-4
Flavia Genua 1 , Julia Butt 2 , Tim Waterboer 2 , David J Hughes 1
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Background
Streptococcus gallolyticus subspecies gallolyticus (SGG) and Fusobacterium (F.) nucleatum have been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology.
Methods
Immunoglobulin (Ig) A and G antibody responses to eleven proteins each of F. nucleatum and SGG were measured in plasma of controls (n = 100) and patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85). Multivariable logistic regression was used to evaluate the association of bacterial sero-positivity with colorectal neoplasia. In a cohort subset with matched data (n = 45), F. nucleatum sero-positivity was correlated with bacterial abundance in both neoplastic and matched normal tissue.
Results
IgG sero-positivity to Fn1426 of F. nucleatum was associated with an increased CRC risk (OR = 4.84; 95% CI 1.46–16.0), while IgA sero-positivity to any SGG protein or specifically Gallo0272 and Gallo1675 alone was associated with increased advanced adenoma occurrence (OR = 2.02, 95% CI 1.10–3.71; OR = 2.67, 95% CI 1.10–6.46; and OR = 6.17, 95% CI 1.61–23.5, respectively). Only F. nucleatum abundance in the normal mucosa positively correlated with the IgA response to the Fn1426 antigen (Correlation coefficient (r) = 0.38, p < 0.01).
Conclusion
Antibody responses to SGG and F. nucleatum were associated with occurrence of colorectal adenomas and CRC, respectively. Further studies are needed to clarify the role these microbes or the immune response to their antigens may have in colorectal carcinogenesis stages.
Graphical Abstract
中文翻译:
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对具核梭杆菌和没食子链球菌蛋白的抗体反应与结直肠腺瘤和结直肠癌的关联
背景
溶没食子链球菌亚种(SGG) 和具核梭杆菌 (F.)与结直肠癌发生有关。在这里,通过多重血清学评估了细菌暴露的免疫反应与结直肠肿瘤进展阶段的关系。
方法
在对照者 ( n = 100) 和结直肠癌 (CRC,n = 25)、晚期腺瘤 ( n = 82)患者的血浆中测量了免疫球蛋白 (Ig) A 和 G 抗体对具核梭菌和 SGG各 11 种蛋白质的反应,或小息肉(n = 85)。使用多变量逻辑回归评估细菌血清阳性与结直肠肿瘤的关联。在具有匹配数据的队列子集中(n = 45),具核梭杆菌血清阳性与肿瘤组织和匹配正常组织中的细菌丰度相关。
结果
具核梭菌Fn1426 的 IgG 血清阳性与 CRC 风险增加相关(OR = 4.84;95% CI 1.46–16.0),而任何 SGG 蛋白或单独的 Gallo0272 和 Gallo1675 的 IgA 血清阳性与晚期 CRC 风险增加相关。腺瘤发生(分别为 OR = 2.02,95% CI 1.10–3.71;OR = 2.67,95% CI 1.10–6.46;OR = 6.17,95% CI 1.61–23.5)。只有正常粘膜中的具核梭菌丰度与 Fn1426 抗原的 IgA 反应呈正相关(相关系数 (r) = 0.38,p < 0.01)。
结论
对 SGG 和具核梭菌的抗体反应分别与结直肠腺瘤和 CRC 的发生有关。需要进一步的研究来阐明这些微生物或对其抗原的免疫反应在结直肠癌发生阶段可能发挥的作用。