Going beyond probiotics: will pathogenic bacteria help us fight eczema in the future?

The human microbiome was the star of this week's science news. In seventeen papers in the journals Nature and PLoS, the Human Microbiome Consortium published the genetic sequences for virtually all the microbes that live in or on the human body. I can't be alone in feeling overwhelmed by the volume of data and analysis. It's clear that the coming years will bring much research into how our body partners with, benefits from, and combats our microbial tenants--which outnumber our cells by a factor of ten.

In a Wall Street Journal story, Michael Fischbach, a professor at the University of California, San Francisco, was quoted as saying "It's likely this work will lead to new treatments for [the inflammatory bowel disorder] Crohn's disease, new treatments for diabetes and metabolic diseases, new treatments for even other diseases, like eczema."

Considering the various locations in the body, the gut and intestines contain the majority of microbes, as you can see in this graphic. A lot of recent work has shown connection between gut flora & systemic inflammation, particularly that involved in asthma and eczema.

A graduate student who reads this blog told me about one of these microbes: Helicobacter pylori. H. pylori has long  lived in the human gut--until the twentieth century, it was apparently the most numerous microbe in the stomach. But it seems that antibiotics have since largely killed it off.

A lot of people would say this was a good thing: only about a decade ago, scientists discovered that H. pylori was the cause of stomach ulcers. But Martin Blaser, a prominent researcher at NYU who made a career out of studying H. pylori, has controversially claimed that it's not just a pathogen but can also do some good. Blaser says H. pylori used to protect us from developing allergic disease. The reason that allergic, atopic diseases are increasing in Western society, Blaser says, is that H. pylori isn't around any more.

The graduate student who wrote me gave me a link to a recent paper in which scientists prevent asthma from developing in lab mice by infecting newborn pups with H. pylori. They show that the way H. pylori is most likely working is that it stimulates the body to produce more regulatory T cells--a class of T cells that put a damper on the activity of other T cells.

In a 2008 story in the Economist, Blaser is portrayed as envisioning a future in which doctors colonize babies' digestive tracts with (presumably) non-pathogenic strains of H. pylori to protect the infants against atopic disease. Certainly a more aggressive form of probiotics than kimchi or yogurt! (Am I allowed to say "probiotics on steroids"?)

I could imagine, also, that there may be no need to use H. pylori at all. If you could arrange things so that a patient grew more Treg cells, that might have the same effect as a H. pylori infection, but a reduced risk of disease caused by the bacteria. Perhaps it will be possible to take a drug that increases the number of Treg cells. Or a patient could donate blood so that Treg cells could be extracted and grown in culture before being reinjected.

I'm excited about this area--admittedly only as speculation about what medicine may hold for us in the distant future. Whenever you're talking about altering the developing immune system, you have to be very careful. Of course, what do antihistamines and steroids do but alter the immune response?

Staph aureus throws a party in untreated eczema patches

We are not alone. Wherever we go, we carry our personal microbiological party along with us--in our gut, in our intestine, and naturally on our skin. We're crawling, even the healthiest of us, with ten bacteria, viruses, protozoa, etc. for every cell in our body.

New research has revealed an interesting difference between the skin microbiomes of patients who do and don't use pharmaceuticals to control their eczema. A recent study in the journal Genome Research finds that Staphylococcus aureus has pooped the party--it dominates the population of bacteria in untreated skin. On the skin of patients who use steroids, calcineurin inhibitors such as Protopic, or antibiotics, S. aureus shares its living quarters much more equitably with its bacterial cousins.

The authors of the paper, led by Heidi Kong and Julia Segre at NIH, used a technique called "16S ribosomal RNA bacterial gene sequencing" to catalog the bacterial population in two body locations at which eczema commonly occurs--the insides of the elbows and the backs of the knees--in 12 kids with eczema and 11 healthy controls.

(They used this type of sequencing because the method usually used to assay bacteria, which is to swab and try to grow a culture, may favor the growth of certain species over others. 16S sequencing provides a snapshot of all bacteria species present at any one time.)

S. aureus dominates flareup regions in patients who don't treat eczema. (Fig 3A.  from Kong et al.)

In the controls and the eczema patients before flareups, the bacterial populations were quite similar, with the eczema patients hosting populations in which S. aureus owned twice as much market share as it did in the controls.But during flares, the main finding was that in the patients who didn't treat their eczema (to be specific: they hadn't taken an oral antibiotic for the previous 4 weeks, or applied a topical treatment in the previous week), 90% of the bacterial population was Staphylococcus, compared to 20% for the patients who had treated their skin.

The scientists observed other shifts in the bacterial population on untreated skin, too. Several other species increased their relative numbers--especially Staphylococcus epidermidis, often thought to be a "commensal"--which I take to mean relatively harmless--species on healthy skin. It appears that S. aureus and S.epidermidis have some kind of symbiotic relationship--the two are helping each other out, or one is parasitic on the other in some way.

Very interesting research, although there's not much for an eczema patient to take away. Naively, one might think that this shows it is better to treat one's eczema than not. But there was nothing about the eczema in untreated skin being worse; the number of patients in the study is small; and there's a lot of variation (of course) among the data for the patients who treated their skin. What did they treat it with? We don't know. Could it be that applying a steroid helps keep down the S. aureus population? That would be weird indeed, because S. aureus folliculitis is a known side effect of strong steroid use. I'll go out on a limb and say that antibiotics are probably better than steroids for keeping S. aureus down in the short term.

One small frustrating point is that the 16S sequencing technique doesn't seem to provide absolute numbers. I'll exaggerate to make the point: Maybe there are 100 bacteria total in your elbow to start, 20 of which are S. aureus, and during a flare there are now 100,000 bacteria, but 90,000 of them are S. aureus. Or maybe there are 90 billion S. aureus out of 100 billion during a flare. This paper doesn't give you any idea of the scale.