Colorectal cancer (CRC) remains one of the major causes of mortality. Hereditary cancers account for a minority of cases while environmental and lifestyle factors are the main driver of sporadic CRC. The pathogenesis of most cases of sporadic CRC is thought to involve a series of genetic mutations, progressing through an adenoma-carcinoma sequence. While CRC has been linked to individual pathogens such as (pks+) Escherichia coli, Fusobacterium nucleatum and Streptococcus gallolyticus, it is probably driven by microbial metabolites and their interaction with the host. The microbiota profiles in patients with adenomatous polyps and colorectal tumors differ from those of healthy controls. It is also noteworthy that changes in the microbiota in CRC occur throughout the colon and are not limited to the tumor itself. Moreover, similar networks of biofilm-forming bacteria are found on oral and gut mucosa in patients with CRC.
While the presence of colonic adenomatous polyps is a risk factor for developing a new CRC, another high-risk group are those who have previously had CRC. However, there are limited data on which patients are at greatest risk of developing a new CRC after the resection of a primary CRC. In particular, the potential role of the microbiome as a marker of risk of developing a new CRC has received limited attention. We and others, have shown persistence of alterations post-resection of CRC in some patients which suggests that the microbiome may have predictive value in this setting, but results have not been uniform. However, earlier studies were conflicting, relatively small, with a short interval since surgery and did not identify the relative proportions of patients for whom the microbiome either reverted toward normal or remained abnormal. Therefore, we have assessed the microbiome in patients after surgical clearance of CRC in comparison with that of apparently healthy controls, patients with adenomatous polyps and those with newly diagnosed CRC.
MATERIALS AND METHODS
Patient recruitment and sampling
The study population included 63 patients post-CRC removal who were recruited during surveillance endoscopy. Also recruited were 18 patients with a new diagnosis of CRC. For comparative analyses we included additional data previously published by us. These included an additional 75 patients with CRC giving a total of 93 patients newly diagnosed with CRC as a comparator group for patients after resection for CRC. Also included were 28 individuals who had undergone polypectomy. While controls included 58 individuals who had no previous medical condition (non-CRC). This study was conducted in accordance with the ethical principles set forth in the current version of the Declaration of Helsinki, the International Conference on Harmonization E6 Good Clinical Practice (ICH-GCP). Eligible patients were identified from case lists the day prior to endoscopy. Patients post-CRC removal were eligible for inclusion if they were undergoing surveillance endoscopy after colonic resection for CRC provided that the original diagnosis could be verified by consultation of the patients’ records, radiological data and histology reports. Only patients with sound clinical, radiological or pathological evidence of previous CRC with subsequent surgery were eligible. Patients post-CRC removal were ineligible for inclusion in this study if they suffered from a medical condition, due to which, in the opinion of the investigator, their participation could put them at increased risk of ill health (e.g. blood clotting disorder). Patients were also ineligible if they were receiving an experimental drug or were in the process of partaking in another clinical trial. Ethical approval was granted by The Clinical Research Ethics Committee of the Cork Teaching Hospitals (Cork, Ireland) under study number APC089 and is specifically applicable to the experiments reported in this paper. The study was conducted from July 2017 to January 2019. Overall, we collected data for each patient covering a range of clinical parameters including history of treatment, tumor stage, tumor location, the duration of time since surgery as well as drug treatment. Data pertaining to habitual diet were also collected using a Food Frequency Questionnaire (FFQ).
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