Species-Level Analysis of the Human Gut Microbiome Shows Antibiotic Resistance Genes Associated With Colorectal Cancer

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.

Fecal Microbiota and Associated Volatile Organic Compounds Distinguishing No-Adenoma from High-Risk Colon Adenoma Adults

“…R. faecis, B. luti, E. rectale , and F. saccharivorans species are members of the Lachnospiraceae family and are SCFA producers that preserve gut homeostasis and protect the intestinal mucosal cells from becoming hyperplastic, dysplastic, or malignant by regulating colonic inflammation [ 35 ]. Moreover, members of the Fusicatenibacter and Roseburia genera, such as F. saccharivorans and R. faecis , are significantly reduced in CRC patients compared to healthy individuals [ 23 , 30 ]. Similarly, B. luti is depleted in CRC patients vs. healthy controls [ 25 , 36 ], consistent with its probiotic properties [ 27 ].…”

“…Members of the Lachnospiraceae family, namely, the Roseburia and Fusicatenibacter genera, were ≈2 times more abundant in NA individuals. At the species level, Roseburia faecis, Blautia luti, Fusicatenibacter saccharivorans, and Eubacterium rectale belonging to the Lachnospiraceae family, as well as Phascolarctobacterium faecium belonging to Potentially pathogenic and carcinogenic, associated with CRC [30].…”

Meta-Analysis and Validation of a Colorectal Cancer Risk Prediction Model Using Deep Sequenced Fecal Metagenomes

“…Furthermore, our study classified the species Sutterella wadsworthensis_A, Anaerotignum sp000436415, and Dialister invisus as CRC-associated bacteria, contributing to the evidence of their pathogenic role [ 46 , 47 , 48 ]. It should be noted that the genus Alistipes was consistently classified as disease-enriched across all the precancerous lesion models [ 49 ].…”

Fecal Microbiota and Associated Volatile Organic Compounds Distinguishing No Adenoma From High-Risk Colon Adenoma Adults

“…faecis, B. luti, E. rectale, and F. saccharivorans species are members of the Lachnospiraceae family and are SCFA producers that preserve gut homeostasis and protect the intestinal mucosal cells from becoming hyperplastic, dysplastic, or malignant by regulating colonic inflammation [35]. Moreover, members of the Fusicatenibacter and Roseburia genera, such as F. saccharivorans and R. faecis, are significantly reduced in CRC patients compared to healthy individuals [23,30]. Similarly, B. luti is depleted in CRC patients vs. healthy controls [25,36], consistent with its probiotic properties [27].…”