Abstract
Gut bacterial toxins are thought to contribute to the development of colorectal cancer (CRC). This study examines the presence of specific gut bacterial toxin genes in stool samples from individuals with colorectal neoplasia (adenomas and/or CRC). The presence of bacterial genes encoding genotoxic or pro-inflammatory factors (pks, tcpC, gelE, cnf-1, AMmurB, and usp) was established by PCR of stool samples from individuals from mainland US (n = 30; controls = 10, adenoma = 10, CRC = 10) and from Puerto Rico (PR) (n = 33; controls = 13; adenomas = 8; CRC = 12). Logistic regression models and multinomial logistic regression models were used to estimate the magnitude of association. Distinct bacterial gene profiles were observed in each sample cohort. In individuals with CRC, AMmurB was detected more frequently in samples from the US and gelE in samples from PR. In samples from PR, individuals with ≥2 gut bacterial toxin genes in stool had higher odds of having colorectal neoplasia (OR = 11.0, 95%: CI 1.0–637.1): however, no significant association between bacterial genes and colorectal neoplasia was observed in the US cohort. Further analyses are warranted in a larger cohort to validate these preliminary findings, but these encouraging results highlight the importance of developing bacterial markers as tools for CRC diagnosis or risk stratification.
Highlights
Sporadic, non-hereditary colorectal cancer (CRC) is a complex and multifactorial disease involving genetic, environmental, and lifestyle risk factors
PCR analyses of stool samples from both mainland US and Puerto Rico (PR) showed a higher colorectal neoplasia in both of the study groups (US and PR cohorts); the degree of the frequency of genotoxic or pro-inflammatory toxin genes detected in samples from individuals with association and the bacterial toxin genes associated varied between the two populations
Despite new insights about the relationships between the gut microbiota and CRC, no methods have been developed that use microbial species or genes as markers for the purposes of screening or risk stratification [38]. In this case-control study, we have examined the association between the presence in stool of a subset of known pro-inflammatory and/or genotoxic bacterial genes and colorectal neoplasia, in samples from two geographically and ethnically distinct populations
Summary
Non-hereditary colorectal cancer (CRC) is a complex and multifactorial disease involving genetic, environmental, and lifestyle risk factors. One of the most currently studied environmental risk factors associated with CRC is the gut microbiota [3,4]. Recent studies have reported that genotoxin-producing E. coli strains are more prevalent in CRC [8,23,24] and that CRC tissues have more mucosa-associated E. coli than seemingly healthy tissues [25]. These findings support the idea that bacteria with genotoxic and/or pro-inflammatory toxins are more abundant in CRC, but that they are in close proximity to the colonic epithelium where they can exert their pro-carcinogenic effects. Nonpathogenic; surrogate marker for Akkermansia muciniphila, a mucolytic bacterium associated with CRC [33]
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