The urinary microbiome associated with bladder cancer

Abstract

Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.

Figure 1

Microbial alpha diversity of urine samples. (a) Observed number of OTUs, (b) Simpson Index. Both alpha diversity metrics were not statistically different between cancer and healthy samples.

Figure 2

Urinary microbiota of male bladder cancer patients and healthy controls. Most abundant taxa are shown at phylum (a), class (b), order (c), family (d) and genus (e) level.

Figure 3

Microbial beta diversity. Dimensional reduction of the Bray-Curtis distance between microbiome samples, using PCoA ordination method, for bladder cancer urines and healthy controls. Data points are coloured according to age in years. Samples do not cluster according to their cancer/healthy status while a moderate clustering according to age is observed.

Figure 4

Differently abundant features between urine samples from bladder cancer patients and healthy controls. Each point represents an OTU belonging to respective genus. 94otu4042 was identified as Jonquetella anthropi, while 94otu9391 and 94otu11945 belong to family Ruminococcaceae and were identified by searching the SILVA rRNA database as Ruminococcaceae UCG-002 and Subdoligranulum, respectively. Features were considered significant if their false discovery rate-corrected p-value was less than or equal to 0.05, and the absolute value of the log2 fold change was greater than or equal to 1.