Abstract
Colorectal cancer (CRC) is the second leading cause of cancer deaths and continuously increases new cancer cases globally. Accumulating evidence links risks of CRC to antibiotic use. Long-term use and abuse of antibiotics increase the resistance of the gut microbiota; however, whether CRC is associated with antibiotic resistance in gut microbiota is still unclear. In this study, we performed a de novo assembly to metagenomic sequences in 382 CRC patients and 387 healthy controls to obtain representative species-level genome bins (rSGBs) and plasmids and analyzed the abundance variation of species and antibiotic resistance genes (ARGs). Twenty-five species and 65 ARGs were significantly enriched in the CRC patients, and among these ARGs, 12 were multidrug-resistant genes (MRGs), which mainly included acrB, TolC, marA, H-NS, Escherichia coli acrR mutation, and AcrS. These MRGs could confer resistance to fluoroquinolones, tetracyclines, cephalosporins, and rifamycin antibiotics by antibiotic efflux and inactivation. A classification model was built using the abundance of species and ARGs and achieved areas under the curve of 0.831 and 0.715, respectively. Our investigation has identified the antibiotic resistance types of ARGs and suggested that E. coli is the primary antibiotic resistance reservoir of ARGs in CRC patients, providing valuable evidence for selecting appropriate antibiotics in the CRC treatment.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide and has led to nearly 1 million deaths in 2020 only (Ferlay et al, 2021)
We discovered 696 representative species-level genome bins (rSGBs), 24,692 plasmids, and 187 antibiotic resistance genes (ARGs) in the gut microbiota, where 25 species were enriched in the CRC group, and 13 species carried ARGs, such as E. coli, A. onderdonkii, B. fragilis, A. muciniphila, and M. torques
More than 90% of species we found had been reported or cultured before, we had discovered unknown species enriched in the CRC group, such as UBA5446 sp900544295 and Anaerotignum sp000436415, with both of the species carrying ARGs
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide and has led to nearly 1 million deaths in 2020 only (Ferlay et al, 2021). Many factors are associated with an elevated risk of CRC, including genetic predisposition, colorectal polyps, inflammatory bowel disease, smoking, and alcohol intake (Wang et al, 2014). Accumulating evidence suggests that long-term, frequent, and/or combined antibiotic use could be risk factors for CRC (Wang et al, 2014; ARGs in CRC Patients Gut. Dik et al, 2016; Cao et al, 2018; Crockett and Nagtegaal, 2019; Zhang et al, 2019). It is worth noting that antibiotic use could increase the richness of antibiotic-resistance bacterial species and the abundance of antibiotic resistance genes (ARGs) in the gut microbiota (Casals-Pascual et al, 2018; Dubinsky et al, 2020). Research on drug-resistant microbiota and resistance genes may help to understand the progression of CRC
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