Bacteria may be responsible for chronic prostatitis

Editors note: Two of our blog posts on aging and the microbiome were recently shared with the website Gut Microbiota for Health. Our readers should take a look!

Link to post.

Some people suffer from an enigmatic diagnosis known as urologic chronic pelvic pain syndrome (UCPPS), also known as non-bacterial chronic prostatitis.  UCPPS’s symptoms are rather similar to urinary tract infections (UTI’s), with a conspicuous lack of a bacterial cause.  In order to diagnose UCPPS doctors must do a bacterial culture of the urine, and if no bacteria grow then the UCPPS diagnosis may be given.  While many believe that this disease may be caused by stress or hormone imbalances, a team of researchers from across the U.S. and Canada investigated if there was a bacterial cause.  As we know, much of the microbiome is unculturable, and can only be identified through genome sequencing.  These researchers hypothesized that bacteria are the true cause of UCPPS, and that UCPPS is similar to UTI, only the bacteria are unculturable, and so basic hospital screens for the bacteria fail to identify them.  The scientists recently published the results of their study in The Journal of Urology.

The researchers did genome analyses on 110 urine samples from male patients suffering from UCPPS and 115 urine samples from normal males with no UCPPS diagnosis.  The results showed that both the groups had approximately 75 bacteria in their urine, all of which would unlikely have cultured in normal hospital assays.  When they compared the types of bacteria between the groups they noticed that Burkholderia cenocepacia was highly abundant in patients with UCPPS but not the control group.  Interestingly, this species had been previously identified as a possible urologic pathogen.

The study had a number of limitations, and the authors admit as much.  For example, it is unclear there sampling procedures would adequately identify any bacteria causing biofilms, and they limited the study to bacteria so fungi and viruses went untested.  Still, it is compelling evidence for a bacterial cause to a disease that had previously been thought to not have a bacterial origin.  These findings really speak to what prominent microbiome scientist, and member of the AMI’s scientific advisory board, Rob Knight recently said in an interview with NPR:  “When you consider the number of diseases where, just over the last five years, it went from being crazy to think the microbes were involved to now being crazy to think the microbes aren't involved, it's amazing how rapidly the evidence has been accumulating.”

Strange, parasitic microbiome bacteria may responsible for inflammatory diseases

Electron micrograph of a type of Actinomyces, the genus of the natural host of TM7, discussed in the paper.

There are many bugs in the microbiome that cannot be cultivated, and thus are incredibly difficult to study using normal culturing techniques.  We only know about these bugs through DNA sequencing, and it often difficult to draw any substantial conclusions from this information.  One such group of bugs that is highly abundant in the microbiome is the bacterial phylum TM7.  TM7 has been associated with numerous inflammatory diseases, like vaginosis, inflammatory bowel diseases and periodontitis, and DNA analysis shows that this bug has the ability to create many toxins.  Studying this bug could lead to breakthroughs in microbiome diseases, but until now it was unculturable.  Recently though, a team of scientists from around the United States were able to cultivate these bacteria and in doing so learned what makes this bacteria so unique, and possibly so pathogenic.  The results were published in PNAS.

The team aimed their investigation at the oral microbiome, because TM7 is abundant in the mouth and highly associated with periodontitis.  They took samples of spit and realized that TM7 only could grow when another bacteria, Actinomyces odontolyticus, was present.  When they cultured these bacteria together in a saliva-like media they realized that the TM7 was physically attached to the surface of A. odontolyticus.  Through further experimentation they learned that TM7 could never grow on its own, and needed A. odontolyticus to replicate.  Furthermore, TM7 is parasitic, and kills A. odontolyticus when they are starved.

The researchers then investigated the pathogenicity of TM7.  They learned that TM7 can evade detection by the immune system for itself and A. odontolyticus.  They also discovered that the particular strain of TM7 they were studying was antibiotic resistant.  Furthermore, sequencing of the TM7 showed the strain had amongst the smallest genomes ever discovered, and relies on the A. odontolyticus for production of many essential molecules, like amino acids.  However, TM7’s small genome is very dense in the production of virulent molecules and toxins, perhaps necessary for its parasitic nature, which could also affect its human host.

This study raises many interesting points about pathogens in the microbiome.  DNA sequencing is a great start to defining the microbiome, but often times culture, or in this case co-culture is necessary to drill down into the true virulence of bacteria.  For instance, prior to this study A. odontolyticus was considered to be associated with many inflammatory diseases, but these researchers showed that it is likely TM7, not A. odontolyticus that is the true culprit.  Alas, the complexity of the microbiome often times reveals many more questions than answers.