Abstract
Dysbiosis has been associated with various diseases and is of major health importance. Dysbiosis leads to microbial translocation, which is the passage of microorganisms, their fragments, or their metabolites from the intestinal lumen into the blood circulation and other sites. The aim of the study was to determine whether microbial translocation occurs in stage II/III-IV colorectal cancer (CRC) patients. The aim was also to evaluate the usefulness of blood PCR for diagnosis of such translocation and correlate the presence of toll-like receptor/vitamin D receptor (TLR/VDR) gene polymorphisms with microbial DNA fragments detected in the blood of CRC patients. Three hundred and ninety-seven CRC patients enrolled in the study. Peripheral blood DNA was analyzed using PCR for the amplification of genomic DNA encoding 16S rRNA, the β-galactosidase gene of Escherichia coli, glutamine synthase gene of Bacteroides fragilis, and 5.8S rRNA of Candida albicans. Significantly higher rates of all microbial fragments, but E. coli, detected were observed in the CRC patients (p < 0.001); such detection of all four microbial fragments was also significantly associated with the metastatic disease (p < 0.001), leading to shorter survival rates (p < 0.001). Tumor location in the right colon also significantly correlated with shorter survival (p = 0.016). Individuals with homozygous mutant alleles of TLR/VDR polymorphisms had significantly higher detection rates of microbial DNA fragments. The detection of microbial DNA fragments in CRC patients highlighted the role of these microbes in cancer development, progression, and patients’ survival.
Highlights
Intestinal dysbiosis, termed as variation in composition and diversity of the gut microbiota, has been associated with multiple metabolic and immune conditions and is considered of major public health importance [1]
A significantly shorter Overall survival (OS) was observed in patients with detectable microbial DNA fragments coding for 16S rRNA, β-galactosidase of E. coli, glutamine synthase gene of B. fragilis, and 5.8S rRNA of C. albicans (p < 0.001, p = 0.039, p < 0.001, and p < 0.001, respectively) (Figure 2E–H)
A significantly higher detection rate of DNA fragments coding for 16S rRNA, glutamine synthase gene of B. fragilis, and 5.8S rRNA of C. albicans was detected in the pool of 397 colorectal cancer (CRC) patients compared to healthy subjects, highlighting the role of these microbes in CRC development
Summary
Intestinal dysbiosis, termed as variation in composition and diversity of the gut microbiota, has been associated with multiple metabolic and immune conditions and is considered of major public health importance [1]. Dysbiosis can lead to the passage of viable microbes from the intestinal lumen through the mesenteric lymph nodes and other sites, known as microbial translocation. Examples include the quantitation of viable microbial colonies isolated from tissues distant to the gut or the intestinal administration of radioisotope-labeled microbes (or their products), followed by measurement of radioactivity in the tissues [9,10]. Blood microbial cultures are often negative, and the repetitive administration of radioisotope-labeled microbes in the human gut is not an easy task
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