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Bacteriocin production by mucosal bacteria in current and previous colorectal neoplasia.

ABSTRACT: BACKGROUND:Optimal therapy for colorectal carcinoma (CRC), a frequently diagnosed malignancy, does not exist. Some of colicins and microcins, ribosomally synthesized peptides by gramnegative bacteria, have shown significant biological activity specifically against different cancer cells in vitro and in vivo conditions. The aim of this prospective study was to evaluate natural colicin and microcin production by large intestinal mucosal bacteria in each stage of colorectal neoplasia and in those with a history of colorectal neoplasia. METHODS:A total of 21 patients with non-advanced adenoma (non-a-A; 16/21 with current and 5/21 with history of non-a-A), 20 patients with advanced colorectal adenoma (a-A; 11/20 with current and 9/20 with history of a-A), 22 individuals with CRC (9/22 with current and 13/22 with history of CRC) and 20 controls were enrolled. Mucosal biopsies from the caecum, transverse colon and the rectum were taken during colonoscopy in each individual. Microbiological culture followed. Production of colicins and microcins was evaluated by PCR methods. RESULTS:A total of 239 mucosal biopsies were taken. Production of colicins and microcins was significantly more frequent in individuals with non-a-A, a-A and CRC compared to controls. No significant difference in colicin and microcin production was found between patients with current and previous non-a-A, a-A and CRC. Significantly more frequent production of colicins was observed in men compared to women at the stage of colorectal carcinoma. A later onset of increased production of microcins during the adenoma-carcinoma sequence has been observed in males compared to females. CONCLUSIONS:Strains isolated from large intestinal mucosa in patients with colorectal neoplasia produce colicins and microcins more frequently compared to controls. Bacteriocin production does not differ between patients with current and previous colorectal neoplasia. Fundamental differences in bacteriocin production have been confirmed between males and females.

SUBMITTER: Kohoutova D

PROVIDER: S-EPMC6966821 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Bacteriocin production by mucosal bacteria in current and previous colorectal neoplasia.

Kohoutova Darina D Forstlova Miroslava M Moravkova Paula P Cyrany Jiri J Bosak Juraj J Smajs David D Rejchrt Stanislav S Bures Jan J

BMC cancer 20200116 1

<h4>Background</h4>Optimal therapy for colorectal carcinoma (CRC), a frequently diagnosed malignancy, does not exist. Some of colicins and microcins, ribosomally synthesized peptides by gramnegative bacteria, have shown significant biological activity specifically against different cancer cells in vitro and in vivo conditions. The aim of this prospective study was to evaluate natural colicin and microcin production by large intestinal mucosal bacteria in each stage of colorectal neoplasia and in ...[more]

PMID: 31948419

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Project description:BackgroundColorectal cancer (CRC) is the 3rd most common cancer worldwide and the Czech Republic has the 6th highest incidence of CRC worldwide. Large intestinal microbiota play in its etiopathogenesis important role. Bacteriocins are proteins, produced by bacteria from the Enterobacteriaceae family. The aim of our prospective study was to assess the colonization of large intestinal mucosa by Escherichia coli strains and to investigate their bacteriocin production.MethodsA total of 30 consecutive patients with colorectal adenoma, CRA (17 men, 13 women, aged 39-79, mean age 63?±?9), 30 patients with CRC (23 men, 7 women, aged 38-86, mean age 67?±?11) and 20 healthy controls (9 men, 11 women, age 23-84, mean age 55?±?15) were enrolled into prospective study. Mucosal biopsies were taken in the caecum, transverse colon and rectum during pancolonoscopy. Microbiological culture, isolation and identification of bacteria followed. Bacteriocin production was assessed by growth inhibition of indicator strains E. coli K12-Row, E. coli C6 (phi), and Shigella sonnei 17. Identification of bacteriocin-encoding determinants and E. coli phylogroups was performed using PCR methods.ResultsA total of 622 strains were isolated and further investigated. A significantly higher frequency of simultaneous production of colicins and microcins was revealed in the group of patients with CRC, when compared to patients with CRA, p?=?0.031. A significantly higher frequency of E. coli phylogroup D was found in patients with CRC, when compared to controls, p?=?0.044. A significantly higher prevalence of bacteriocinogeny was confirmed in patients with advanced adenoma when compared to patients with non-advanced adenoma, p?=?0.010. Increasing bacteriocinogeny was associated with an increasing stage of CRC (assessed according to TNM classification). Either E. coli phylogroup B2 or E. coli phylogroup D were isolated in biopsies of patients with right-sided CRC. A statistically higher incidence of E. coli phylogroup B2 was found in patients with right-sided CRC when compared to patients with left-sided CRC, p?=?0.028.ConclusionsLarge intestinal mucosa of patients with more advanced colorectal neoplasia is colonized with more virulent strains of E. coli and higher production of bacteriocins is observed in these patients when compared to those with less advanced colorectal neoplasia.

Project description:Objective To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis.Data sources Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries.Study selection Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events.Data extraction Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria.Results 15 randomized controlled trials (12?234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated.Conclusions Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile.Registration PROSPERO (CRD42015029598).

Dataset Information

Bacteriocin production by mucosal bacteria in current and previous colorectal neoplasia.

Publications

Bacteriocin production by mucosal bacteria in current and previous colorectal neoplasia.

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