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reported in

Table 1

. At each taxonomic level, some microbial

populations were found to be present exclusively in one or

two regions. The beta-diversity could not differentiate

between the three different areas of the prostate

( Fig. 2

).

No significant correlation between the microbial burden

(at each taxonomic level) and the extent of intraprostatic

inflammation, and the inflammatory cell density, the

prostate-specific antigen levels, and the Gleason score

was observed (data not shown).

4.

Discussion

In this study, we have characterized for the first time the

microbiome of the pathological prostate by using an

ultradeep pyrosequencing approach. Besides confirming

the presence of a local prostate-specific microbiome

[23]

,

along with the overall

nonsterile

environment of the

prostate, we were able to ascribe a certain microbiome

profile specifically to a certain histological tissue type.

Due to the unavailability of normal, healthy prostate

specimens, we used the nontumoral area selected within

the tumoral prostate specimens. If, on the one hand this is a

limit, on the other hand the comparison of matched T, PT,

and NT areas minimized interpatient confounding factors

such as diet or lifestyle, which are already known to

significantly impact microbiome composition

[5–10]

.

The similarity in the microbiome profile observed among

the areas was not surprising due to the narrow proximity of

the lesions and the field-effect. Nevertheless, we could

observe, at each taxonomic level, a gradual change in the

richness of some bacterial groups between the T and PT

region, as well as between the PT and NT region of the

prostate. Moreover, the characterization of the PT region-

associated microbiome allowed us to add on the concept

that specific microbial populations may find in the

pathological prostate niche the favorable soil to set

themselves and outcompete other species. Indeed, the

microbiome profile associated to the PT region was more

similar to the T with respect to the NT region, thus

indicating a possible role of the PCa extracellular environ-

ment in favoring the establishment of specific microbial

populations. These may in turn affect tumor growth or

progression through different mechanisms such as modu-

lation of host immune responses and extracellular matrix

composition. In this context, Alfano et al

[16]

reported that

Enterobacteriaceae

are able to modify the extracellular

matrix by secreting enzymes such as alkaline proteases and

elastases. This pilot study cannot answer the question

Table 1 – Bacterial relative abundance in prostate samples at all taxonomic levels reported as median (first quartile to the third quartile)

percentage. Only taxa with a median value >0.1 in at least one of the areas analysed are shown (statistical analysis: Friedman’s test and

Dunn’s posthoc test for T vs PT vs NT; Wilcoxon rank test for T + PT vs NT)

Taxa

T

PT

NT

Statistical significance

Phylum

Actinobacteria

82.2 (72.6–90.6)

78.1 (72.7–86.9)

75.3 (53.7–82.9)

NS

Firmicutes

10.3 (8–18.3)

11.5 (6.5–17)

15.1 (11.3–32.3)

NS

Proteobacteria

2.6 (0.66–9.2)

4.4 (2.1–8.4)

4.2 (1.8–10.5)

NS

Class

Actinobacteria

82.2 (72.6–90.6)

78.1 (72.8–86.9)

75.3 (53.7–82.9)

NS

Bacilli

9.5 (6–12.3)

10.8 (5.9–15)

14.6 (9.1–32.3)

NS

Gammaproteobacteria

0.35 (0.16–1.3)

0.83 (0.4–1.1)

0.34 (0.06–1.4)

NS

Alphaproteobacteria

0.39 (0–3.1)

2.1 (0.57–4)

0.9 (0.1–5.1)

NS

Clostridia

0.39 (0–2.7)

1 (0.36–1.6)

0.25 (0–1)

NS

Order

Actinomycetales

82.2 (72.6–90.6)

78.1 (72.8–86.9)

75.3 (53.7–82.9)

NS

Bacillales

7.56 (3.5–8.7)

8.3 (3.4–12.5)

4.9 (3.7–7.3)

NS

Clostridiales

0.39 (0–2.7)

1 (0.36–1.6)

0.25 (0–1)

NS

Lactobacillales

0.8 (0.1–2.5)

1.3 (0.9–2.6)

7.9 (0.4–19.3)

p

<

0.05 (T + PT vs NT)

Rhodobacterales

0 (0–0.65)

0.71 (0–2.4)

0 (0–0.94)

NS

Gemellales

0.85 (0.52–1.2)

0.56 (0.23–1.3)

0.89 (0.24–1.4)

NS

Family

Propionibacteriaceae

60.3 (47.5–70)

60.4 (50.3–67.9)

49.8 (45.5–62.2)

NS

Corynebacteriaceae

14.4 (7.8–25.6)

12.4 (10–20.5)

6.7 (2.8–11.7)

NS

Staphylococcaceae

7.5 (3.5–8.7)

8.2 (3.3–12.5)

4.3 (3–6)

p

<

0.05 (T + PT vs NT)

Tissierellaceae

0 (0–1.6)

0.55 (0–1.3)

0.15 (0–0.48)

NS

Rhodobacteraceae

0 (0–0.65)

0.71 (0–2.41)

0 (0–0.94)

NS

Enterobacteriaceae

0 (0–0.39)

0 (0–0.1)

0 (0–0.22)

NS

Gemellales

0.81 (0.52–1)

0.56 (0.23–1.3)

0.79 (0.23–1)

NS

Micrococcaceae

0.13 (0–0.43)

0.65 (0–1.2)

0 (0–1.3)

NS

Aerococcaceae

0.26 (0.06–0.91)

0.71 (0.12–1.4)

0 (0–0.13)

NS

Streptococcaceae

0 (0–0.21)

0.5 (0.06–1.3)

5.1 (0.27–17.4)

p

<

0.05 (T, PT vs NT)

p

<

0.05 (T + PT vs NT)

Genus

Propionibacterium

60.1 (47.3–69.6)

60.3 (48.7–67.4)

49 (42.2–61.8)

NS

Corynebacterium

14.4 (7.8–25.6)

12.4 (10–20.5)

6.7 (42.2–61.8)

NS

Staphylococcus

7.5 (3.5–8.7)

8.2 (3.3–12.5)

4.3 (3–6)

p

<

0.05 (T + PT vs NT)

Paracoccus

0 (0–0.48)

0.26 (0–1.3)

0 (0–0.33)

NS

Gemellales

0.81 (0.52–1)

0.56 (0.23–1.3)

0.79 (0.23–1)

NS

Micrococcus

0 (0–0.25)

0.24 (0–0.81)

0 (0–0.21)

NS

Streptococcus

0 (0–0.21)

0.5 (0.06–1.3)

5.16 (0.27–17.3)

p

<

0.05 (T, PT vs NT)

p

<

0.05 (T + PT vs NT)

NS = not significant; NT = nontumor; PT = peri-tumor; T = tumor.

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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