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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