Infections are one of the hypothesized ways by which chronic inflammation may affect the prostate. The understanding of the urinary microbiome with respect to PC patients may help to understand the relationship between the urinary microbiome and chronic inflammation in the prostate which is important in establishing strategies for PC prevention.
In the current study, the overall prevalence of significant bacteriuria in PC patients between 51–90 years was 26 (86.66%), which is in contrast (46.5%) with the findings of Heidler et al.,[15] this may be due to difference in processing method as urine test strips were used for analysis and also the grouping of samples i.e., preoperative urine culture, prostate tissue culture and postoperative urine culture. A study carried out by Koeijers et al.,[16] on urinary tract infections (UTI) in men reported a prevalence of 236 (56%). Similar trends are noticed in uropathogenic studies in India or internationally accounting for low percentages of UTI in males when compared to females. Sood and Gupta [17] in 2012 (Jaipur, Rajasthan) found 130 (37.67%), where patients with ≥ 61 years accounted for (47.28%) of total cases which tends to be similar to our study. Rangari et al.,[18] (Uttar Pradesh) reported 137 (45.66%), whereas, Prakash and Saxena [19] in 2013 (Meerut City) found 52 (35.14%) in their individual studies. In a comparative study conducted by Gupta et al.,[20] in 2014 between the Northern and Southern states of India found a prevalence of 292 (35.1%), 192 from Northern India, males accounting (for 47.40%) and 100 from Southern India, males being (43%) respectively. The notable variance could be a result of the large difference in sample size or men with PC are more likely to be prone to uropathogens and may experience uncomplicated UTIs.
In this report, identification and molecular characterization of the urinary microbiome in prostate cancer patients indicate that the urinary microbiota of most men is dominated by polymicrobial isolates 22 (85%), whereas mono microbial isolates were 4 (15%) which is in contrast with the findings of Heidler et al.,[15] (25%) mix culture and 15 (75%) pure isolates. The variability may be due to the low sample size used in their study. Thereby, indicating a high population of bacterial species in the urine of PC patients when compared to normal healthy men.
In the present study, out of 48 isolates, gram-negative organisms were most prevalent 34 (71.00%) than gram-positive organisms 14 (29.00%) which tends to be similar to the works reported in India earlier.[16, 17, 18, 19, 20] In our study we found 48 isolates in which Escherichia coli was the predominant organism 15 (31.00%) followed by Klebsiella pneumoniae 11 (23.00%), Enterococcus faecalis 9 (19.00%), Staphylococcus aureus 5 (11.00%), while the least prevalent organisms were Pseudomonas aeruginosa and Proteus vulgaris 4 (8.00%) which tend to be in correspondence with previous studies related to uropathogens.[16, 18, 19, 21] It has been reported that E. coli and Enterococcus are present in significant amounts in the seminal fluid and expressed prostatic secretion (EPS) of patients with PC compared to benign prostatic hyperplasia (BPH) which account for a significant degree of inflammation in patients with PC. [22]
Research has shown that in cases of acute prostatitis and some chronic prostatitis, bacteria are the primary etiological agents. Acute infections are predominated by E. coli strains (uropathogenic) whereas chronic prostatitis may be caused by Klebsiella, Enterococcus, Pseudomonas, E. coli and Proteus species. The effects of these infections in long term generate an inflammatory response within the prostate and result in patient morbidity and establishment of preneoplastic lesions. In bacterial prostatitis microorganisms implicated are Enterococcus sp. and E. coli additional organisms like Klebsiella sp., Proteus mirabilis, Serratia sp. and Pseudomonas sp. have been recognized,[23] which are relevant to this study. Previous studies have shown that, E. coli as the most predominant isolates among all the isolated bacteria amongst PC patients’ samples which is corresponding to our report 15 (31.25%). [16, 17, 18, 19, 20] The possible role for asymptomatic prostatic inflammation caused by infectious microorganisms and PC development are supported by several lines of evidence. E. coli outer membrane has an enzyme Phospholipase D (PLD) attached to it which usually causes BPH. If the transitional zone of prostate gland experiences repeated colonization and destruction by E. coli or PLD release leading to prostate enlargement.[24] Research has also shown that prostatic inflammation is prompt by infections of prostate with uropathogens E. coli and proinflammatory species P. acnes which may cause alterations in morphology (dysplasia and hyperplasia), a characteristic which should be taken in consideration for studies on carcinogenesis. Whereas E. coli also decrease the NKX 3.1 tumor suppressor in prostate.[25] Furthermore, pathogenic strains of E. coli which possess genomic island ‘pks’ in charge of colibactin are found to influence breaks in DNA of humans.[26] Fascinatingly, in a newly performed study examining patients of acute bacterial prostatitis (ABP) ≥ 70% of E. coli isolates were expressing colibactin whereas gene cluster cytolethal distending toxin was carried by one strain.[27] They posit that E. coli produced genotoxic toxins found in ABP could provide to ensuing carcinogenesis and probably explaining epidemiological figures which suggest greater risk for PC in patients with prostatitis history.[27] Considering these details, a possible link can be established between prostatic inflammation and PC development if E. coli continues to be an organism of specific interest.
In our study, predominant E. coli (n = 15) showed resistance to Cefotaxime (60.66%), Ciprofloxacin (46.67%) and Nitrofurantoin (6.66%). A study carried out by Sood and Gupta [17] reported E. coli (n = 214) showed resistance to Cefuroxime (66.67%), Ciprofloxacin (74.75%) and Nitrofurantoin (5.77%) and also similar findings have been noticed in other studies. [18, 19, 20, 28] The second common pathogen K. pneumoniae (n = 11) showed resistance to Ciprofloxacin (72.73%) followed by Cefotaxime, Cefuroxime (63.64%) and Nitrofurantoin (45.45%) which are in agreement with previous studies. [18, 19, 20, 28] The remaining isolates E. faecalis, S. aureus, P aeruginosa and P vulgaris showed similar resistant patterns in context to studies conducted by other researchers in India. Slight variations in the resistant percentages may be due to difference in strains of bacteria as well as the demographic conditions of the respective regions. Our findings indicate a polymicrobial population and also an urgent need to develop a restrain to resistance of these drugs or curtail their use in uncomplicated infections. Further research needs to be conducted in large sample size.