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

Abstract

The human gut microbiota in colorectal cancer patients have a distinct population compared to heathy counterparts. However, the activity (gene expression) of this community has not been investigated.

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

“…Moreover, the pattern of expression of n -butyrate-synthesizing genes indicates a switch in substrate specificity to favor acetone production from acetoacetyl-CoA ( Text S1 ), suggesting a limited supply for the host to metabolize. We have shown the attenuated activity of 22 n -butyrate-producing species in the CRC microbiome ( 25 ), which corroborates these data. Carnitine is important for osmotic adaptation of the microbiota, suggesting that they are under increased osmotic stress.…”

“…We observed evidence of microbial adaptation to highly acidic conditions during CRC, at the molecular ( Fig. 3A ) and phylogenetic ( 25 ) levels. The Na + -H + antiporter subsystem, which modulates H + potential across the bacterial membrane, was downregulated, implying high extracellular proton concentrations and low pH.…”

“…We also observed enhanced expression of genes conferring resistance to vancomycin and β-lactams. These data demonstrate that the CRC gut can promote expression of antibiotic resistance determinants; this may be due to the enhanced activity of microbes carrying antibiotic resistance, including ESKAPE and Enterobacteriaceae species ( 25 ).…”

“…Microbial RNA sequencing (RNA-seq) data argue that the CRC gut environment is more acidic, fluctuates in osmotic potential, and is less saturated with H 2 O 2 compared to the control gut. The aerobic microbial populations of both conditions, grown in LB over 24 h until stationary phase, were enriched with 60% to 70% of E. coli based on 16S rRNA gene sequence profiling ( 25 ) (Table 3 in Data Set S1 ) and are a well established model system known to be highly resistant to acidic conditions ( 30 ) and can survive in the mammalian stomach ( 31 ). Hence, we tested whether acidity and other environmental factors (osmotic and oxidative pressures) regulate E. coli Arg- and Lys-dependent acid resistance systems by quantifying the expression of amino acid decarboxylases, speA ( 32 ), adiA ( 33 ), and cadA ( 34 ) ( Table 2 ; Fig.…”

“…Taxonomic analysis of this microbiome revealed elevated activity of the oral cavity for Enterobacteriaceae , ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter spp. ), and other clinically relevant pathogenic species ( 25 ); the same community displayed enhanced activity of numerous specific virulence determinants. The CRC microbiota transcribed exopolysaccharide, heteropolysaccharide, and capsular polysaccharide biosynthesis genes more readily ( Fig.…”