Bladder Cancer

A Cancer Treated With Bacteria, in an Organ Full of Them

The evidence here is emerging rather than settled, but the starting point is unusually concrete. Bladder cancer is the ninth most common cancer worldwide. The standard treatment for early-stage disease has been a live bacterium for decades, long before anyone thought about the microbiome. What's changed recently is the discovery that the bladder it's put into was never sterile either.

A treatment that predates the field

Bacillus Calmette-Guérin, usually called BCG, is a weakened strain of Mycobacterium bovis, a relative of the tuberculosis bacterium.

It was developed as a tuberculosis vaccine. It's now standard treatment for high-risk bladder cancer that hasn't invaded the muscle wall, delivered directly into the bladder through a catheter.

It doesn't kill cancer cells. It provokes a strong local immune response, and that response clears the tumour cells.

The mechanism has never been fully worked out. What is known is that the bacterium attaches to the bladder lining and triggers an inflammatory cascade that recruits immune cells to the area.

Between 30% and 50% of patients don't respond, and for them the alternative is often removal of the bladder. Predicting who will respond has been a long-standing problem.

The bladder isn't sterile either

The assumption that urine is sterile came from culture methods designed to find infections, which miss most resident organisms.

Better sequencing showed a resident bladder community. That raises an obvious question about a treatment that works by introducing a bacterium into that space.

Researchers examined 87 people, 29 with benign conditions and 58 with bladder cancer, profiling the bacteria in their urine.

The compositions differed between benign and cancerous cases. More usefully, responders to BCG had different urinary communities from non-responders.

Two Bifidobacterium species were more common among responders, and their presence was associated with longer periods free of recurrence.

Source: Differential Urinary Microbiome and Its Metabolic Footprint in Bladder Cancer Patients Following BCG Treatment

Variety inside the tumour

A separate study looked at bacteria within the tumour tissue itself rather than in urine.

Patients who responded to BCG had significantly greater bacterial richness and variety inside the tumour environment than non-responders.

Lactobacillus and other ordinary commensal organisms were enriched in responders.

The proposed explanation is that these bacteria help prime the local immune response. They influence which signalling molecules are produced and how readily the cells that present antigens to the immune system activate, which is exactly the process BCG depends on.

If that holds, the treatment isn't acting on a blank surface. It's acting on a community that either supports or blunts what it's trying to do.

Source: Microbiome and immunotherapy in bladder cancer: The missing link

Where the gut comes in

The bladder community doesn't arise independently, which is where the intestine enters the picture.

Bacteria reach the bladder from the gut and surrounding skin, so the gut is the upstream source for much of what lives there.

The gut also shapes the systemic immune response that BCG relies on, in the same way it shapes response to other immunotherapies.

That gives a practical concern. Broad-spectrum antibiotics are used frequently in bladder cancer care, for urinary infections and around procedures. Each course disturbs both communities.

Reviews of this field now flag judicious antibiotic use as something to weigh carefully, given what's known about antibiotics reducing responses to immunotherapy elsewhere.

Loss of protective organisms including Lactobacillus, Bifidobacterium and Ruminococcus, alongside enrichment of inflammatory ones, is the pattern associated with worse outcomes across both sites.

What this means for you

Blood in the urine needs prompt investigation, since it's the commonest first sign of bladder cancer and is usually caused by something less serious, and smoking is by far the largest modifiable risk factor. In addition, the research above found people who respond to standard bladder cancer immunotherapy carrying more varied bacteria in both urine and tumour tissue, with specific commensal groups enriched among responders. A varied, plant-rich diet supports the same gut bacteria this research ties to the groups found in responders, and which also seed the bladder community upstream. That's the same idea behind GutLab, everyday gut health starts with regularly feeding the microbiome a broad range of plant-rich ingredients.