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relative to the assessment of a causal link as opposed to

noncausal associations among tumor and baseline/back-

ground colonization. However, the gradual difference in

microbiome, among areas, suggests at least a noncasual

correlation; of importance, it also reduces the risk of results

due to sampling artefacts. Broader studies are mandatory to

ascertain whether the described profile is associated to,

correlated with, or even responsible for the onset of the

disease.

Due to its topography, the prostate may be reached by

members of the skin and gut microbiota, which may

eventually be able or not to survive within the particular

prostate microenvironment and outcompete other

microbes. Accordingly, the prostate prokaryotes, which

have been identified, belong to both these environments.

The high abundance of

Propionibacterium

spp., which

resulted to be composed mainly by

P. acnes

, is consistent

with the observed proinflammatory role of

P. acnes

and

supports its reported association with PCa

[13,14,24]

. An

ascending urethral route is also suggested by the frequent

isolation of these species from urine

[25]

. Moreover,

previous studies have reported the presence of vaginal

P.

acnes

in cultures from healthy women and patients with

vaginosis

[26] ,

therefore also indicating a possible sexual

transmission.

Viceversa

, the presence of

Enterobacteriaceae

was restricted to the T samples.

Enterobacteriaceae

have

already been shown to be more abundant in other

inflammatory and neoplastic conditions

[27,28]

, which is

in line with a progressively increased inflammatory

environment surrounding cancer cells. Interestingly, the

higher abundance of

Corynebacteriaceae

, basically repre-

sented only by

Corynebacterium

spp

.

, in the prostate lesions

is consistent with the reported great capacity of these

species to form biofilm and adhere to extracellular matrix

components such as fibronectin, often with tissue-invasive

potential

[29]

. Moreover,

Corynebacteriaceae

have also been

previously identified as potential causal agents of urinary

tract infections or urethritis

[30]

.

Viceversa

, the almost

exclusive presence of

Streptococcus

spp

.

in NT areas

supports the concept that this member of

Lactobacillales

may belong to the normal prostate microbiome ecosystem

and may help to maintain a physiological and beneficial

relationship with the host extracellular environment. Of

relevance, members of the

Corynebacteriaceae

family, such

as

P. acnes

and

Streptococcus

strains, are known to live and

compete in other body environments such as the skin or the

oral cavity. Inverse relationships between these strains, and

to a reduced extent with other bacteria, were observed

within the same prostate region at the genera level (data not

shown), whose significance needs to be further investigated

with methods able to identify bacteria, including

Streptococci

, at the species level.

Differences in terms of microbial environment are

expected to exist among the different zones of the prostate,

especially when comparing the transition zone versus the

peripheral zone. This may be of particular relevance when

[(Fig._2)TD$FIG]

Fig. 2 – Beta diversity analysis. Principal component (PC) analysis plot of weighted UniFrac metrics for tumor (yellow dots), peri-tumor (blue dots), and

nontumor (red dots) areas of prostate samples. Multivariate analysis shows that the microbiome of the prostate is similar among the patients and that

the samples from the three prostate areas do not cluster by their overall microbiome composition. However, for some patients, nontumoral areas

appear distant from the tumor and peri-tumor samples.

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 6 2 5 – 6 3 1

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