A Meta-analysis on the Association of Colibactin-producing pks+ Escherichia Coli With the Development of Colorectal Cancer

Marcianne Elaine Gaab, BS; Prim Olivette Lozano, BS; Danica Ibañez, BS; Korina Diane Manese, BS; Fatima May Riego, BS; Raphael Enrique Tiongco, RMT, MSMT; Pia Marie Albano, RMT, MSc, PhD

Disclosures

Lab Med. 2023;54(1):75-82. 

In This Article

Abstract and Introduction

Abstract

Objective: Previous studies on the association between pks+ Escherichia coli and colorectal cancer (CRC) demonstrated conflicting results. Hence, we performed a meta-analysis to obtain more precise estimates.

Methods: Related literature was obtained from PubMed, ScienceDirect, Google Scholar, and Cochrane Library. Data were then extracted, summarized, and subjected to analysis using Review Manager 5.4 by computing for the pooled odds ratios at the 95% confidence interval.

Results: Overall analysis showed that individuals carrying pks+ E coli had a greater risk of developing CRC. Subgroup analysis further showed that individuals from Western countries carrying pks+ E coli and individuals with pks+ E coli in their tissue samples had increased risk of developing CRC.

Conclusion: Results of this meta-analysis suggest that individuals with pks+ E coli have a greater risk of developing CRC. However, more studies are needed to confirm our claims.

Introduction

Colorectal cancer (CRC) is the third-most diagnosed (10%) and second-most deadly (9.4%) cancer in the world. In 2020 alone, more than 1.9 million CRC cases and more than 930,000 CRC-related deaths were reported. CRC incidence and mortality rates are mainly higher in males.[1] Furthermore, the incidence and mortality trends of CRC are increasing in developing countries rather than following the decreasing trends found in developed countries.[2]

Studies have shown that the risk of acquiring CRC increases with an unhealthy diet, alcohol consumption, obesity, and physical inactivity. A diet mainly composed of processed meat and high levels of fat with an inadequate intake of fruits, vegetables, and whole grains further increases this risk.[1,3] Other major risk factors include a family history of CRC, polyps in the colon or rectum, and inflammatory bowel disease.[4] Interestingly, evidence has shown that the body's innate intestinal microbiome is also a significant contributor to CRC development.[3,5,6]

The gut microbiota consists of microorganisms such as bacteria under the Bacteroides, Bifidobacterium, Lactobacillus, Eubacterium, Peptococcus, Fusobacterium, Clostridium, and Escherichia genera.[7,8] These microorganisms form a symbiotic relationship with the host, wherein they function to metabolize nutrients, provide and maintain the structural integrity of the gut mucosal barrier, and protect the host against pathogenic microorganisms.[9] An imbalance in the normal composition of intestinal microflora results in gut dysbiosis, which may involve a loss of beneficial microbial signal, loss of overall microbial diversity, or pathobiont expansion.[10]

Dysbiotic states, which alter the host's physiological functions, have often been associated with extraintestinal diseases.[11] Strains of Escherichia coli, mainly those belonging to the B2 phylogroup, are the predominantly isolated bacteria from the colon.[12–15] The virulence of most E coli B2 strains has been attributed to the polyketide synthase (pks) genomic island. This pks island encodes nonribosomal peptide synthases, polyketide synthases, and hybrid peptide-polyketide synthases, which synthesize a genotoxic compound called colibactin. Production of this toxin then induces double-stranded DNA breakage and activates the DNA damage checkpoint pathway, ultimately leading to cell death.[16]

Among the members of the Enterobacteriaceae family, colibactin-producing E coli B2 strains have been prevalent in CRC tissue and stool samples.[17–19] Studies have found that pks+ E coli persisted in the colon, inducing colon inflammation, epithelial damage, and cell proliferation in vivo.[15,20] In animal models, pks+ E coli enhanced tumor growth in infected mice,[17,21] suggesting its potential role in colon carcinogenesis. However, previous studies on the association between pks+ E coli and CRC demonstrated conflicting results.[17,19,22,23] Hence, this meta-analysis was conducted to obtain more precise estimates and determine whether pks+ E coli is associated with CRC development.

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