Research using lab-grown bladder sheds light on urinary tract infections

Urinary tract infections (UTIs) occur when bacteria infect the urinary system, including the urethra, bladder or kidneys.

For most people, they are an acute infection which clears up within days of antibiotic treatment.

But for some, the burning feeling when they pass urine and the constant trips to the bathroom fade away but then return weeks later. A recurrent UTI is defined as having two UTIs within six months or three within a year. And chronic UTIs occur when there is a deep-seated infection, usually in the bladder, that presents with daily symptoms that do not go away.

However, recent research involving lab-grown human bladders has increased our understanding of chronic UTIs. It is estimated that UTIs affect more than 400 million people worldwide each year. They are most common in women; more than half of adult women will have at least one in their lifetime.

Recurrent or chronic urinary infections are a particular problem for perimenopausal and post-menopausal women.

For some, the only prospect of relief comes when doctors prescribe ongoing antibiotic treatment. Most UTIs are caused by a type of Escherichia coli (E.coli) that normally lives harmlessly in the gut. Problems start when bacteria travel up the urethra into the bladder. Women have a much shorter urethra and the urethral opening is also close to the anus, making the bugs’ journey easier in women.

So why doesn’t treatment work in people with chronic UTIs?

Sometimes, bacteria from the original infection appear to survive treatment and later re-emerge. Animal studies have shown that E.coli can invade cells lining the bladder and multiply inside them, forming clusters of bacteria that are partly shielded from the immune system and some antibiotics.

But recent research using a lab-grown human “mini-bladder” suggests part of the answer may lie inside the bladder wall itself. Scientists in Switzerland and Germany have now built a 3D model of the human bladder using lining from human bladder cells. The model reproduces the lining’s multiple cell layers, its exposure to urine and aspects of a real bladder filling and emptying.

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When the researchers infected these mini-bladders, E.coli penetrated into deeper layers of tissue. They then treated the infection with fosfomycin, an antibiotic used to treat UTIs. Some bacteria survived in a temporary form without a normal cell wall. These altered bacteria were able to persist within deeper layers of bladder tissue. Once the antibiotic was removed, they returned to their usual form and restarted the infection.

The researchers also found that prolonged exposure to highly concentrated urine weakened the connections between bladder cells, making the tissue more vulnerable to bacterial invasion and reducing the effectiveness of antibiotic treatment.

The mini-bladder findings have recast UTI as a disease shaped by interactions between bacteria, bladder tissue, the immune system and the chemical and physical conditions inside the bladder.

What are the current recommendations for preventing UTIs?

Drinking more water can help. In a trial of 140 premenopausal women who drank less than 1.5 litres of fluid a day, those asked to add another 1.5 litres of water averaged 1.7 bladder infections over a year, compared with just over three infections among those who continued their usual intake.

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Cranberry juice has its advocates for reducing recurrent UTIs, although the scientific evidence for its use remains contradictory. Phage therapy is another option where bacteria-killing viruses called bacteriophages could help target bacteria persisting in bladder tissue. They have been shown to reduce clusters of harmful bacteria within bladder cells, while leaving protective bacteria such as Lactobacillus alone.

Another preventive treatment is methenamine hippurate, a non-antibiotic urinary antiseptic. Researchers are also exploring the potential of probiotics to introduce beneficial bacteria into the urinary tract to out-compete harmful microbes.

One of the treatments for recurrent UTIs with the strongest evidence is the use of a locally applied vaginal oestrogen (such as Vagifem).

It is suitable for women during and after the menopause.

mhouston@irishtimes.com