The Colorectal Cancer Microbiota Alter Their Transcriptome To Adapt to the Acidity, Reactive Oxygen Species, and Metabolite Availability of Gut Microenvironments

Abstract

The human gut microbiota has the genetic potential to drive colorectal cancer onset and progression; however, the expression of this genetic potential during the disease has not been investigated. We found that microbial expression of genes that detoxify DNA-damaging reactive oxygen species, which drive colorectal cancer, is compromised in cancer.

The Colorectal Cancer Gut Environment Regulates Activity of the Microbiome and Promotes the Multidrug Resistant Phenotype of ESKAPE and Other Pathogens

“…Metatranscriptomic analyses for these genes showed their transcription was significantly greater in CRC. This suggests that these antibiotic resistance determinants are not regulated by hydrogen peroxide, and this is consistent with our observation that H 2 O 2 oxidative pressure is not a major feature of CRC, in contrast to the control gut environment ( 27 ). Expression of cls and marA was enhanced in CRC microbes in response to H 2 O 2 .…”

“…5 ). This aligns, at least in-part, with our functional metatranscriptome analyses that the gut microbiome displayed greater expression of antibiotic resistance determinants in CRC, including β-lactams and efflux pumps ( 27 ). The factors responsible for enhancing Enterobacteriaceae activity, such as nutrient availability or colonocyte invasion, are yet to be established.…”

“…2 ). This is in line with transcription of n -butyrate-metabolizing genes/pathways ( 27 ). We also found that activity of several Streptomyces species (major antibiotic-producing bacteria which control microbial community composition [ 28 ]) was diminished in CRC ( Table 1 ).…”

“…This argues that activity of specific microorganisms is regulated independently of abundance in CRC. Metatranscriptome levels of many clinically relevant bacteria, such as ESKAPE, Enterobactiaceae, and oral pathogens was significantly elevated in CRC, which is consistent with enhanced β-lactam and vancomycin resistances of this microbiome ( 27 ). Responses of aerobes of the CRC and control gut microbiota in vitro differed to environmental pressures, particularly to acid pressures.…”

“…One of the striking features of the CRC gut environment is that it differs from the control counterpart with respect to environmental acidic, osmotic, and oxidative pressures ( 27 ). We proposed that such factors may, in part, regulate expression of AB resistance genes.…”