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Page 10 of 17 Peng et al. Microbiome Res Rep 2024;3:5 https://dx.doi.org/10.20517/mrr.2023.47

Table 3. Urinary or intratumoral microbiota relevant to recurrent bladder cancer and response to BCG
Microbiota related to Microbiota related to BCG
Research Sample Ref.
recurrence response
Wu et al. 2018 Urine samples from 29 BC and 18 Herbaspirillum ↑ [17]
HC Gemella ↑
Bacteroides ↑
Porphyrobacter ↑
Faecalibacterium ↑
Aeromonas ↑
Zeng et al. 2020 Urine samples from 40 NMIBC Anoxybacillus ↑ [86]
Massilia ↑
Thermomonas ↑
Brachybacterium ↑
Micrococcus ↑
Nocardioides ↑
James et al. 2023 Urine samples from 29 NMIBC Aerococcus ↑ [87]
Ureaplasma ↓
Escherichia/Shigella ↓
Knorr et al. 2021 Tissue samples from 26 BC Corynebacterium ↑ [91]
Pseudomonas ↑
Knorr et al. 2022 Tissue samples from 47 BC Lactobacillus ↑ [90]
Corynebacterium ↓
Hussein et al. Urine samples from 43 BC and 10 Serraia ↑ [92]
2021 HC Brochothrix ↑
Negativicoccus ↑
Escherichia-Shigella ↑
Pseudomonas ↑
BC: Bladder cancer; BCG: Bacillus Calmette-Guérin; HC: healthy controls; NMIBC: non-muscle invasive bladder cancer; UC: urothelium carcinoma.

on Bacillus Calmette-Guérin (BCG)-treated NMIBC patients noted a higher relative abundance of
Aerococcus in urine from patients with relapse, while Ureaplasma and Escherichia/Shigella elevated in urine
from patients without relapse . A healthy gut microbiota is often characterized by high richness , but a
[88]
[87]
high richness of microbial communities in the urinary system may not be a healthy phenomenon. The
significantly increased richness of the urinary microbiome suggests a higher risk of recurrence, but whether
specific responsible bacteria can be identified to quantitatively assess this risk still needs further research
and clinical verification.

Microbiota and BCG intravesical instillation
BCG is a type of vaccine made up of an attenuated strain of Mycobacterium bovis. BCG intravesical
instillation is the gold-standard adjuvant treatment for NMIBC with a high risk of progression and induces
initial complete response rates of 55%-65% for high-risk tumors and 70%-75% for carcinoma in situ .
[89]
Although Mycobacterium bovis is not normally present in the urinary tract, its unique role described in the
treatment of bladder cancer highlights the relationship between microbes and antitumor immunity, more
precisely, the relationship between microbiota and tumor immune microenvironment.

The link between urinary microbiota and BCG response remains controversial [Table 3]. Knorr et al.
demonstrated a significantly increased abundance of Lactobacillus in BCG responders and Corynebacterium
in BCG non-responders , which contradicts their previous conclusion of the enrichment of
[90]
Corynebacterium in BCG responders . Hussein et al. reported that the abundance of Serraia, Brochothrix,
[91]
Negativicoccus, Escherichia-Shigella, and Pseudomonas was significantly increased among NMIBC patients
who responded to BCG treatment . The above evidence did not identify consistent bladder microbes that
[92]
may be associated with BCG response, but suggested that the bladder microbiota may influence the
antitumor effect of BCG. Current comprehension of underlying mechanisms of BCG in treating bladder
cancer includes direct cytotoxic effects and complicated antitumor immune responses that rely on