Dr. A. Lenore Ackerman (UCLA) is a rising star in the IC/BPS research community. Her specialty is the study of the microbiome, the bacterial communities that live within our body and, to our benefit, the urinary tract. In 2023, she was the first to suggest that some patients with IC/BPS and bladder pain may be struggling with an infection caused by lactobacillus iners, a new pathogenic lactobacillus that was discovered a few years ago.
During the AUA 2024 meeting last Spring, she pondered “Could IC be really reflective of some type of infection or problem that we are not recognizing because we are still using technology that are more than 100 to 150 years old? ” Some of these patients have a history of infections and will say that the symptoms are identical but that antibiotics don’t work anymore, leaving them very confused and frustrated.
Interestingly, multiple studies have found that patients with bladder pain symptoms have elevated levels of inflammatory markers (i.e. iL6, iL8, etc.) that also happen with UTI. There is new data that shows inflammatory dysregulation pathways found in UTI are also upregulated in some IC patients which, she said “circumstantially implicates infection in some IC patients.” So what kind of bacteria could be involved?
The Urinary Biome
The microbiome are the bacterial communities living within the human body that have a symbiotic role in maintaining our health. Interestingly, they differ based upon location with different communities found in the bowel, the vagina, skin and mouth. In many instances, these have been linked to human disease.
One challenge that we face is that the urinary biome has not been studied extensively so urology researchers study the findings for the bowel to understand what could be happening in the urinary tract.
In the GI tract, the microbiome produces neurotransmitters that interact with our nervous system. They outcompete pathogens for food and the resources. They help to regulate skin health and epithelial junctions. They produce natural antimicrobial compounds (aka natural antibiotics) that can kill pathogens. They also prime our immune system. Dr. Ackerman said “We think these effects are also happening in the bladder even thought it’s different tissue.”
What happens when the microbial community changes? When the normal organisms living in the GU tract are messed up and no longer supporting normal activity? An abnormal community develops, called a dysbiotic community, aka dysbiosis.
Dr. Ackerman said “We think these communities lead to changes in epithelial integrity, maybe they allow some toxins in urine to seep into the bladder wall and cause changes there, including increased vascularity, changes neurosensitivity, general irritations of muscles, acids seeping into tissue… and maybe that’s what is leading to the symptoms that some patients are experiencing.”
What is the IC/BPS Urobiome?
Several studies have been done to study the urobiome in IC/BPS. While no “smoking gun” of a bacteria emerged in all patients, they did find that our urinary biome had less diversity and an overabundance of lactobacillus. Lactobacillus has always been considered a normal, good resident in the vagina and bladder.
Dr. Ackerman conducted her own study in her lab at UCLA. She, too, found that IC patients had less diversity of normal bacteria and more lactobacillus. But then, she looked at the data based upon the age of her patients and that’s where things started to get interesting. She said “Patients under the age of 45 are largely dominant in lactobacillus but as we get older, our microbiome changes. Patients over the age of 60 have many more bacteria.” The flaw with the early IC microbiome studies is that they included patients of all ages in their analysis.
Dr. Ackerman took it a step farther and looked at her data based upon patient phenotype and this is where the breakthrough occurred. She found that bladder wall driven patients are dominant in a newly discovered species of lactobacillus, known as lactobacillus iners. Pelvic floor driven patients had a normal biome. Patients with pain beyond their bladder had many more bacteria in their biome, including vibrio, halomonas, enterobacter and more.
Dr. Ackerman said “Lactobacillus Iners is unique because it is gram negative, it doesn’t behave like other lactobacillus to kill candida, produces minimal hydrogen peroxide and produces a toxin like gardnerella that damages cells.” She continued “Iners becomes highly enriched in the vaginal biome in patients using antibiotics.” It appears to be an opportunistic lactobacillus that grows rapidly and dominates the biome when antibiotics have killed the other good lactobacillus.
What else happens after antibiotic use? The good bacteria that normally keep fungi in check are destroyed, thus allowing fungus (candida) to grow. She said “Increased fungal levels are also found in IC/BPS and the levels go up when patients are having flares.” This was confirmed in an MAPP research study several years ago. She continued “fungal signatures correlate with bladder pain. Specifically candida increases with pain overall.”
Dr. Ackerman emphasized that much more research is needed study the urinary biome and how it changes in various diseases, including IC/BPS. We do know, for example, that patients with Hunner’s lesions have been found to have an overabundance of virus in their urine (Epstein-Barr and Polyoma). Dr. Ackerman has shown that an overabundance of lactobacillus iners and candida could be playing a role in bladder pain but not pelvic floor driven pain.
What can we do to protect our biome?
Dr. Ackerman ended her presentation with a cautionary note to the doctors who attended. She encouraged doctors to stop prescribing antibiotics without first confirming that a UTI is actually present. She said “Antibiotics are not harmless. There are systemic effects for antibiotics which might include the enrichment of species like lactobacillus iners and the over expansion of fungal species like candida. These may have long term very long term bigger consequences that we must keep in the back of our heads.”
Patients should also consume a diet rich in prebiotic and probiotic-rich foods, such as fermented vegetables, yogurt, and kefir, that can help to promote the growth of beneficial bacteria in the urobiome. Prebiotics, which are types of dietary fibre that feed the good bacteria, and probiotics, the live microorganisms themselves, work together to maintain a diverse yet balanced urobiome.
Source: Quentin Clemens MD, Henry Lai MD, A. Lenore Ackerman MD, Emerging Concepts in Interstitial Cystitis/Bladder Pain Syndrome. AUA 2024 149IC. May 5, 2024.
