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Peng et al. Microbiome Res Rep 2024;3:5 https://dx.doi.org/10.20517/mrr.2023.47 Page 3 of 17

Table 1. Urinary or intratumor microbiota in BC patients and healthy individuals
Research Sample Cancer group Ref.
Xu et al. 2014 Urine samples from 8 UC and 6 HC Streptococcus ↑ [15]
Bučević Popović et al. 2018 Urine samples from 12 BC and 11 HC Fusobacterium ↑ [16]
Actinobaculum ↑
Wu et al. 2018 Urine samples from 29 BC and 18 HC Acinetobacter ↑ [17]
Anaerococcus ↑
Rubrobacter ↑
Sphingobacterium ↑
Pederzoli et al. 2020 29 BC tissue samples and 29 paired controls Burkholderia ↑ [18]
Mansour et al. 2020 10 BC urine samples and 14 BC tissue samples Bacteroides ↑ [19]
Akkermansia ↑
Klebsiella ↑
Clostridium sensu stricto ↑
Enterobacter ↑
Liu et al. 2019 22 BC tissue samples and 12 adjacent controls Actinobacteria ↑ [21]
Proteobacteria ↑
Firmicutes ↓
Bacteroidetes ↓
Brucellaceae ↑
Acinetobacter ↑
Anoxybacillus ↑
Parra-Grande et al. 2022 32 BC tissue samples and 26 adjacent controls Actinobacteria ↓ [22]
BC: Bladder cancer; HC: healthy controls; UC: urothelium carcinoma.

[20]
that suggests its metabolic activity and functional significance . Pederzoli et al. detected an enrichment of
Burkholderia in bladder cancer tissue compared to non-neoplastic tissue . Mansour et al. showed that the
[18]
microbiota in the mucosal tissue of bladder cancer patients was different from that in urine samples, and the
abundance order from high to low was Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and
[19]
Cyanobacteria, respectively . m o n g t h e m , Akkermansia, Bacteroides, l o s t r i d i u m s e n s u stricto,
A
C
Enterobacter, and Klebsiella, as “five suspect genera”, were significantly increased in bladder cancer tissue
compared to urine samples, indicating their potential involvement in the onset of bladder cancer. Liu et al.
found significantly decreased Firmicutes and Bacteroidetes, together with increased Proteobacteria and
Actinobacteria at the phylum level in cancer tissue . Concurrently, Cupriavidus spp, unclassified
[21]
Brucellaceae, Acinetobacter, Escherichia‐Shigella, Sphingomonas, etc. were significantly increased at genus
level in tumor tissue compared to noncancerous tissue. Although there was no statistically significant
difference in α-diversity between the two groups, the lower degree of bacterial diversity in tumor tissue
compared to noncancerous controls was apparent based on differences observed in β-diversity. Parra-
Grande et al. found that the Actinobacteria showed stark differences when comparing tumor tissue and
adjacent normal tissue and pointed out that the diversity of the microbiota in bladder cancer mucosal tissue
was lower than that of paired normal controls . Theoretically, focusing on the comparison between
[22]
intratumoral microbiota and paired tissue microbiota seems to pave the way for further causal research and
exploration of potential mechanisms.

Current studies of urinary tract microbiota are mostly based on 16S rRNA variable region sequencing,
which can detect a small number of bacteria but has limitations, such as the inability to distinguish between
[23]
live and dead bacteria or to detect nonbacterial organisms, including fungi and viruses . Sequencing based
on variable regions of 16S rRNA is sufficient to identify genera, but they are unlikely to distinguish species
precisely . Therefore, most of the current bladder cancer microbiome characterization reflects the genus
[24]
level of microbiota composition, which may not represent the true species richness of microbiota samples.
No statistically significant association was found between urinary tract infection and bladder cancer in the
[25]
past , which may need to be confirmed by further high-quality studies concentrating on specific bacterial