If You Can’t Culture It, It Doesn’t Exist

We were taught in medical school that the bladder was sterile. That’s because urine is sterile. So naturally, so is the bladder, right?

Wrong. It turns out that there are numerous organisms in the bladder, and that probiotics that might change the microbiome in the bladder may enhance effectiveness of chemotherapy for bladder cancer.

The reason we thought bladder was sterile is several-fold. For one thing, the organisms in the bladder won’t grow in culture. In the fine scientific tradition of “if you can’t culture it, then it doesn’t exist” we honor in biology, we thought urine was sterile because we couldn’t culture any bacteria out of normal urine. Now with PCR, we can detect bacteria DNA in the urine.

Of course, this begs some important questions, such as “are those scientist who claim they find m. avium paratuberculosis in the blood, and those scientist who claim they find organisms in the brain–are they actually right?”

For example, there has been a long-running theory that Crohn’s disease and perhaps ulcerative colitis is caused by Mycobacterium avium paratuberculosis(MAP). MAP, which is related to the bacteria that causes TB, causes a disease called Johne’s disease in cattle that is similar to Crohn’s disease. Johne’s disease was identified around the same time Crohn’s disease was identified–both are fairly recent diseases

Crohn’s disease is actually very similar to gastrointestinal TB, which used to be the predominant form of TB. It’s not clear why TB is mostly pulmonary now. In any case, the controversy exists because MAP is widespread in cattle and has become more and more prevalent; pasteurization does not kill MAP effectively; and people with Crohn’s disease seem to be more likely to be infected with MAP. That last point has been a point of contention though. Different groups have had different results when they have looked for MAP in people. However, there seems to be evidence that IBD responds to antibiotics.

What is clear is that like multiple sclerosis, Crohn’s disease is distributed only in countries and places where people drink milk. If you overlay the map of Crohn’s disease and the map of areas where milk is consumed, they overlap almost perfectly.

The story is similar in Alzheimer’s disease. Recently, evidence has been accumulating that beta amyloid may be involved in host defenses. For example, beta amyloid seems to possess antibacterial properties. And mice engineered to overexpress beta amyloid are highly resistant to bacteria, even when the bacteria is injected directly into the brain. The beta amyloid encapsulates the pathogens, just like traditional anti-microbial peptides (which the beta amyloids resemble biochemically) do. This is part of a number of studies suggesting that Alzheimer’s disease may be triggered by infections.

These hypotheses are intriguing, and at this point, not widely accepted. Of course, though, we have the story of h. pylori as a precedent, to teach us that even the implausible can eventually become accepted as mainstream.