Investigating the drivers of Interstitial Cystitis and Bladder Pain Syndrome, including the role played by our microbiome ecosystems

Interstitial Cystitis and Bladder Pain Syndrome (IC/BPS) are considered a diagnosis of exclusion, meaning, there is no single test to definitively confirm the condition; instead, a diagnosis is made based on the patient's symptoms and the process of ruling out all other possible causes of the symptoms.

One exclusion criteria of IC/BPS is not obtaining a positive urine culture on tests looking for infection. However, sensitivity of urine testing is poor, so this isn't a solid criteria in my opinion.

It is estimated that IC/BPS affects up to 400,000 patients in the UK, with almost 90% being women between 40 to 70 years of age

Lets explore the condition and traditional symptom management:

What are the symptoms.

IC/BPS sufferers may differ in their exact presentation, but the overarching symptoms include, most commonly:

• Bladder pain and discomfort, or generalised pain in the lower tummy, this may be continuous or come in ‘flares’.
• Increased urgency and frequency to urinate, even when the bladder is not full.
• Waking in the night more than once to urinate. And less commonly:
• Urine leakage.
• Painful sex.

Overall the conditions are characterised by inflammation of the bladder’s lining.

In interstitial cystitis, which is the more specific clinical diagnosis, physical changes on the bladder lining may be present, known as Hunner’s lesions (inflammatory patches) or glomerulations (small haemorrhages seen during cystoscopy).

Hunner’s lesions are present in up to 10-20% of IC suffers. Whilst glomerulations are present in IC sufferers, they are also present in non sufferers, so their presence is not deemed a reliable diagnostic marker.

These conditions are often hugely distressing and emotionally taxing, whilst also being confusing for sufferers given they are often told the cause of their condition is unknown.

Prevalence and conventional treatment

About 90 percent of patients with this condition are women and the average age of onset is 40, although people of any age can be affected.

Women with this condition are more likely to have had frequent urinary tract infections and to have had previous gynaecological surgery than women without IC.

Treatment is multifaceted, but options are all based on ‘symptom management’, given the aetiology (cause/es) of the conditions is not fully understood. As a result, traditional treatment, such as pain relief, instillations, bladder distention, anti histamines, anti depressants and physical therapy, are highly variable in performance for patients.

What are the possible drivers of these conditions?

Emerging evidence is beginning to highlight several potential underlying drivers in these conditions. Current thinking is that IC and BPS are most likely multifactorial, meaning several mechanisms are likely to be involved in sufferers, lets explore these now:

Leaky bladder lining / bladder lining defects

One area of research has focused on dysfunction of the bladder lining, called the glycocalyx. The glycocalyx consists mainly of substances called mucins and glycosaminoglycans (GAGs). This layer normally protects the bladder wall from toxic effects of urine. In those with IC, this layer has been found to be ‘leaky’, and as a result causes mild to major bladder discomfort.

The question here, is what makes it ‘leaky’ in the first place? One theory is that bacteria trigger sensory pathways in the bladder, i.e. ‘inflammatory’ microbes may be causative; this aligns with the finding that many IC/BPS sufferers have previously experienced UTIs, or their symptoms start after a bladder infection. Inflammation driven by an imbalanced gut microbiome has also been considered in the research as a contributing factor to inflammatory processes in the bladder.

Immune dysfunction

Some immune dysfunction is thought to play a role in these bladder conditions. For example, a higher-than-average number of IC patients have autoimmune conditions, and when some sufferers are given immune modulating treatment such as anti histamines and steroids, symptoms improve.

Studies have found increased mast cells, T-cells, and other immune cells in the bladder walls of people with IC too (which often trigger further injury to the bladder lining, causing the ongoing cycle).

A microbial imbalance / low level infection

Recent advances in testing have highlighted the potential role of the human microbiome, particularly urinary, vaginal, and gut microbiota, in the pathophysiology and treatment of IC/BPS.

Gut microbiota

Preliminary studies find some correlation between dysbiosis in the gut and IC; the mechanics discussed lie in the gut’s ability to modulate immunity and inflammation, thereby an imbalanced gut microbiome may initiate or exacerbate bladder inflammatory processes contributing to pelvic pain.

Urinary microbiota.

Urobiomes (bladder microbial environment) of those suffering with IC have been found to have inflammatory Staphylococcus as the most prevalent and abundant bacteria, followed by common uropathogen E.coli. Other studies find altered urinary microbiota in comparison to healthy control subjects, including a heightened fungal presence in those having an IC ‘flare’, suggesting other microbes may play a role too.

Although the influence of the ‘urobiome’ remains an under-explored area of research, there is certainly evidence to imply microbial dysbiosis in IC/BPS may amplify local and systemic inflammatory responses, contributing to persistent symptoms.

Vaginal microbiota

Given the vagina’s proximity to the urethra, any pathogenic bacteria present in the vagina can be a risk factor for the health of the bladder. Many UTIs are caused by a reservoir of pathogenic bacteria in the vagina.

More studies are needed in this area of women’s health to fully understand if a connection exists, but its safe to say a healthy vaginal microbiome is an important aspect of overall gynaecological, urological and pelvic health.

I’m particularly passionate about microbial dysbiosis as a driver in IC/BPS pathogenesis. Speaking from clinic experience, in many cases of IC I investigate the microbiome of the gut, urine and vagina (which are commonly imbalanced), with a view to optimising health in these areas, and subsequently improving symptom management. Alongside other interventions, such as bladder lining healing and nervous system attention, and other bespoke needs, this can bring about positive change.

Pelvic Floor dysfunction

In nearly all sufferers of IC/BPS there is some degree of pelvic floor dysfunction. Pelvic floor muscles can carry a lot of tension causing them to become hypertonic (tight): this tightness can impact the function of the bladder and the surrounding tissues, for example, contributing to the natural inclination to urinate more frequently.

Nerve sensitivity

The bladder has a rich network of nerves (sensory, autonomic and pelvic/pudendal). In IC/ BPS, inflammation from bladder lining damage, immune activation and mast cell activity can cause these nerves to become overactive and hypersensitive, sending pain signals to the brain, even when the bladder is empty.

Hormone shifts

It's noteworthy that the most common time of onset of these conditions occurs around the time of peri-menopause and menopause in a female. Considering the bladder is lined with oestrogen receptors, the drop in this hormone will have a major impact on this organ: from reducing tissue integrity and strength to altering the protective microbial environment (specifically seeing a reduction in anti microbial properties capable of fighting off infections).

Hormonal shifts may well play a role in a woman’s susceptibility to these conditions, most likely due to the changes in tissue integrity and microbial environments.

Women also report a cyclical flare pattern in line with their period, suggesting daily shifts in hormones impact this condition too (oestrogen can increase the activation of mast calls, a key component of the inflammatory response in IC).

Summary.

In summary, research suggests IC/BPS is multifactorial, arising from a combination of immune, microbial, hormonal, bladder lining and nervous system factors. Individuals will have unique drivers, and also other confounding health factors which can contribute to the uniqueness of these conditions between sufferers.

A cascade of events

I find the microbial element of these conditions fascinating and most pertinent. I suspect in many cases, an inflammatory microbial presence impacted the bladder lining, and from here a cascade of events takes place, involving the GAG layer, immune and nervous system response, allowing these to become ‘ dysfunctional’.

Optimising microbiome sites is therefore always a key step in removing any inflammatory trigger that may be driving symptoms, as part of a wider plan to optimise health and symptom management for better quality of life in those suffering.

We hope you found this insightful.  Please see our next blog: Managing Interstitial Cystitis and Bladder Pain Syndrome symptoms: tools and avenues to consider.  

References

Lim, Y., Leslie, S. W., & O’Rourke, S. (2024). Interstitial Cystitis/Bladder Pain Syndrome [Internet]. StatPearls Publishing. Last update October 7, 2024. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.

Fallon, J., Tabansky Stern, I., Laurent, M., Birder, L., Moldwin, R. M., & Stern, J. N. H. (2023). The immune system in Interstitial Cystitis/Bladder Pain Syndrome and therapeutic agents. Continence, 8, 101057. doi:10.1016/j.cont.2023.101057.

Matthews, J. C., & Schaeffer, A. J. (2006). Patients with chronic pelvic pain: endometriosis or interstitial cystitis? European Journal of Obstetrics, Gynecology, and Reproductive Biology, 125(2), 164–173. doi:10.1016/j.ejogrb.2005.11.009. (derived from PMC3015726)

Contribution of the Microbiome to Interstitial Cystitis/Bladder Pain Syndrome: A Mini Review. Continence / European Urology Focus. (2025)(?) S2405-4569(25)00008-2.

Diagnosis of Interstitial Cystitis/Painful Bladder Syndrome in Patients With Overactive Bladder — Strategies for Differentiation. European Urology. (2006) 50(6): 1301–1310. PMC1832106.