Colorectal Neoplasia and Microbiota: Does Left Equal Right?

Many studies, including our own, have shown that colorectal cancer (CRC) is related to changes in the microbiome of the colon. However, there are limitations in most studies and questions remained unanswered. Some early data showing that the microbiome in the left vs right colon are different.

The aim of this study is to investigate the microbiome (including bacteriome, virome, and fungome) of adenoma/CRC comparing the left (distal to splenic flexure) vs right side (proximal to splenic flexure) of the colon.

1. Many studies, including our own, have shown that colorectal cancer (CRC) is related to changes in the microbiome of the colon

   1. Certain bacterial phyla are more frequently presented in CRC
   2. Bacterial diversity is reduced in CRC
   3. Co-occurrence of bacterial phyla and exclusion are identified in CRC
   4. Besides bacteriome, viromes have been found associated with CRC
   5. These changes in the pattern may actually be used for diagnosis and prognosticate purposes.
2. However, there are limitations in most studies and questions remained unanswered

   1. Most studies used stool sample and data of tissue (tumor and adjacent normal tissues) may not be available
   2. Most studies take adenoma and CRC as one condition, without differentiating the findings according to tumor location
   3. Most studies have separate bacteria, virus and fungi. There is a lack of data on their interaction
   4. Most studies have identified either microbiome without correlating them with the genomic of the host
3. We know that not all CRC are the same. It has been known that rectal and colonic cancer are not the same. Furthermore, proximal (right) CRC and distal (left) CRC may not be the same.

   1. Studies have shown compare to L-CRC, patients with R-CRC are older, more female (Iaocopetta B et al. Int J Cancer 2002)
   2. Studies have also shown that the genomic make up of L-CRC and R-CRC are different. R-CRC are more likely to have family cancer syndrome (HNPCC), mostly diploid, less frequent to have loss heterozygosity, less TP53 mutations and more MSI and CIMP, and the gene expression are different (Glebov et al. Cancer Epi, Biomarker and Prevention 2003)
   3. The response to therapy might also be different in the L-CRC compare to R-CRC
   4. Recent studies show that the clinico-pathological and molecular features of early-onset (\<50 years) CRC varies according to tumor location. (Peres J et al. Am J Cancer Res 2015). In the R-CRC in this group, germline mutation is more common (MLH1, MSH2, MSH6, PMS2 and EPCAM). Adenomas tend to be larger, flatter and more likely to have high-grade dysplasia and villous histology
   5. Recent studies have also shown that the clinic-pathological and molecular feature of in the late-onset CRC (70-80 years) varies with tumor location (Brandariz et al. Oncotarget 2018). There are more sporadic MSI, more BRAF mutation and the adenoma/CRC are likely to be mucinous.
4. Studies comparing the microbiome of L-CRC vs R-CRC has not been many. There is some early data showing that the microbiome in the left vs right colon are different.

The aim of this study is to investigate the microbiome (including bacteriome, virome, and fungome) of adenoma/CRC comparing the left (distal to splenic flexure) vs right side (proximal to splenic flexure) of the colon.

Eligibility Criteria:
Inclusion Criteria:

1. \>18 years of age, with the informed consent of the study-specific colonoscopy examination method and samples collection
2. have an indication for a scheduled colonoscopy, either as an investigation of colorectal symptom or as part of a CRC screening
3. for those who are known to have either adenoma or CRC, colonoscopy is arranged for endoscopic submucosal dissection (ESD) or endoscopic mucosectomy (EMR)

Exclusion Criteria:

a. known history of coagulopathy b. recently on antithrombotics or antiplatelets c. recently on antibiotics, prebiotics, probiotics and symbiotics d. anticipated prolonged standard colonoscopy procedure at endoscopist's discretion e. consent cannot be obtained

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