Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract.

Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.

Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer.

Fusobacterium nucleatum (F. nucleatum, Fn) is associated with the colorectal cancer (CRC). Fn-infection could induce significant levels of serum Fn-specific antibodies in human and mice. The objective of this study was to identify Fn-infection that elicit a humoral response in patients with CRC and evaluate the diagnostic performance of serum anti-Fn antibodies. In this work, we showed the mean absorbance value of anti-Fn-IgA and -IgG in the CRC group were significantly higher than those in the benign colon disease group and healthy control group (P < 0.001). The sensitivity and specificity of ELISA for the detection of anti-Fn-IgA were 36.43% and 92.71% based on the optimal cut-off. The combination of anti-Fn-IgA and carcino-embryonic antigen (CEA) was better for diagnosing CRC (Sen: 53.10%, Spe: 96.41%; AUC = 0.848). Furthermore, combining anti-Fn-IgA with CEA and carbohydrate antigen 19-9 (CA19-9) (Sen: 40.00%, Spe: 94.22%; AUC = 0.743) had the better ability to classify CRC patients with stages I-II. These results suggested that Fn-infection elicited high level of serum anti-Fn antibodies in CRC patients, and serum anti-Fn-IgA level may be a potential diagnosing biomarker for CRC. Serum anti-Fn-IgA in combination with CEA and CA19-9 increases the sensitivity of detecting early CRC.