Friday, June 15, 2012

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?

9 comments:

  1. Also influenza has been shown to have a link in possibly being preventative for airway hyperreactivity, a proxy for asthma (http://phys.org/news/2010-12-flu-infections-asthma.html gives a summary of http://www.jci.org/articles/view/44845). The key here seems to be childhood infections may tilt the immune system towards tolerance, whereas in adults they may provoke an immune response. The mechanism for this is not yet clear. Also, the paper isn't by the Blaser lab - it's from a German group (led by Anne Mueller) that is collaborating with them. But Dr. Blaser - who is known for his discovery of a protein involved in the pathogenesis of H. pylori - has a lot of interest in H. pylori and this model.

    H.P. isn't necessarily a pathogen, however - until recently it was part of the normal intestinal microbiota. While it is associated with ulcers and stomach cancer, he suggests there may be a link between the rise of antibiotics, loss of H. pylori, and the rise of other cancers (such as esophageal). So eradication of the microbiota that may have co-evolved with us may have unpredictable side effects.

    Paper: Ching et al. Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. J Clin Invest. 2011;121(1):57–69. doi:10.1172/JCI44845.

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  2. Questioning it allJune 15, 2012 at 7:45 PM

    "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"

    How careful do you think they are with the 36 vaccines they now get before 5 years old? They just figured out antibiotics/pain medications/statins etc etc etc can have all these unintended negative side effects. When do you think they will figure that out with vaccines?

    "Also influenza has been shown to have a link in possibly being preventative for airway hyperreactivity, a proxy for asthma (http://phys.org/news/2010-12-flu-infections-asthma.html gives a summary of http://www.jci.org/articles/view/44845). The key here seems to be childhood infections may tilt the immune system towards tolerance, whereas in adults they may provoke an immune response"

    Instead of all the flu vaccines- maybe kids should get some actual infections to prevent all this atopy?

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  3. In the old days, not that long ago, many kids who got actual infections died. If you go to old graveyards you can see the proof.

    Vaccines for major childhood diseases stopped that. Vaccines are one of humanity's greatest achievements. They have been shown to be safe and effective and I am not aware of any credible epidemiology showing that vaccines cause trouble other than rare adverse reactions that take a toll far, far smaller than the diseases the vaccines are designed to fight.

    A lot of people would like to blame vaccines for a bunch of problems including atopy. I think the issue is that conditions such as atopy and autism emerge in the first few years at the same time that a child's immune system is developing--at the same time that it is critical to vaccinate children to protect them from terrible diseases. So you give kids vaccinations, and in about the same time frame you notice that some of them have eczema or asthma or whatever and some people feel angry and want to find a scapegoat. They blame vaccines.

    The current understanding is that eczema is a skin barrier disease first and an allergic/auto-immune disease second. As you must know, it's influenced by genetics, early childhood therapy, geographic location, and diet. It may indeed turn out some day that scientists will show that vaccines are somehow also a factor. If that happens, we can reformulate or reschedule the vaccines to reduce the impact. It would be a terrible mistake to stop vaccinating our children.

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  4. Thanks for the links, KMO. This is a fascinating area.

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  5. Questioning it allJune 16, 2012 at 11:25 PM

    To be clear, I never suggested we discontinue vaccinating children. While I do think that vaccines do have a use in modern medicine and in our healthcare system I think we are foolish to think that with such a burden of vaccines (35+) on our systems from such a young age is not doing a lot of long term damage. I found it interesting that you had said "Whenever you're talking about altering the developing immune system, you have to be very careful" yet fail to consider this as possible cause for the absolute avalanche of immune-challenged children we have in the US today. I know you suffer from it, and your children- wait until you bring them to school and you see all the anaphylactic/eczema covered and highly allergic children there. You (and they) certainly won't be alone in itchy (and otherwise) suffering. I know personally four children that can't ever go out to eat at restaurant because of their life threatening allergies. A protein of casein, peanut or egg could kill them in minutes. No sharing lunches at school- or anywhere for that matter and an epipen in a bum bag attached at all times. Could you imagine the stress that is on them and their parents?

    "Vaccines are one of humanity's greatest achievements". We must be also open enough to consider that our understanding of immunity is changing. We are using older vaccines, while we keep piling more new ones on to the schedule without adequate studies proving they are safe when used in combination,when there can be a synergistic effect. The studies have NOT been done. Please check for yourself.

    Now, according to Scientific American, the polio vaccine (oral) is now giving more case of polio than it is preventing.

    http://www.scientificamerican.com/article.cfm?id=polios-last-act


    The death rates for most of the diseases we use the vaccines for were miniscule even before the vaccines came along, and you can find that information easily in the literature. In the West, it was our plumbing and sanitation, as well as better nutrition, and yes, antibiotics and better health care (and not even including vaccines) is what really helped us prevent most of the infections and deaths.

    Vaccines are now and have been useful for our health. We really owe it to our children to take apart and study in every which way these inoculations that could be damaging their quality of life and long term health. Like I said, these studies have NOT been done.

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  6. Thanks for your thoughtful reply. My comment was worded strongly because I wanted to make my position clear. I see anti-vaccination websites and I meet parents who don't vaccinate their kids and I am appalled.

    My initial statement that we need to be careful about monkeying with the developing immune system was aimed at the dangers of applying radically new therapies (e.g. gene therapy) without widespread, thorough testing. Vaccination isn't radical.

    But it's a valid question whether loading kids up with too many vaccines in a few sessions of multiple injections might have side effects including increasing the statistical risk of kids getting allergies.

    I don't have the time to explore this complex issue all at once, nor to expand my scope beyond eczema. You can expect me to give the topic a fair treatment though.

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  7. I can read a lot of scientific studies about this issue. What I only know for now is that probiotics can really aid digestion and can boost immune system. I've personally attest to this fact because I've been taking my daily dose of probiotics supplements for a couple of years already as advised by my doctor. So whenever there will be news saying probiotics can treat this or that, I won't be surprised. It really is a great supplement for me.

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  8. @ValerieJune: That's also been my experience. After making and eating my own home made yoghurt and kimchi since last fall, my eczema has cleared up 99%. I still almost can't believe it. I have tried *many* things: creams, eating different stuff which should aid in getting healthier skin, staying away from food with a lot of nickel in it (I have nickel allergy), steroid creams, etc. Some of the things did work somewhat, but none one of them had a lasting and good effect, compared to probiotics from home made unpasteurized yoghurt and kimchi.

    When you count the live bacteria in pills, it is in the billions, whereas in home made unpasteurized it is trillions, so this form is clearly more efficient, and cheaper. My expenses are *very* limited, the only ingredients needed being milk and vegetables, which don't cost a lot.

    R

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  9. I have had severe stomach cramps for a little over a month, along with dry mouth and vertigo when upright. The only things that have come from tests so far are low lipase and slightly high indirect bilirubins. The really curious thing is that my dogged cases of dandruff, eczema ( on face and torso), and athlete's foot, which I've had for 20 years all went into complete remission a few weeks prior to this. I used to control these symptoms with apple cider vinegar, but in the months preceding this, I had made an effort to control skin issues through lifestyle changes, more veggies and fish, less bread and sugar, and dropped ACV altogether. Because of the cramps and diarrhea, I started back on bread, etc, but my skin stuff remains MIA.

    I had thought that the skin conditions were due to Candida, and I had assumed that I was starving it out. Candida and dandruff have relationships with lipase that I am just beginning to become familiar with, but I am not clear as to what the nature of that relationship is or which direction it flows. Interestingly, there's not a lot of information about low lipase or what causes it.

    I have started taking probiotics in the last few days, which may be normalizing the stools but not doing much for the cramping so far.

    I can't find much about spontaneous remission of eczema, etc, but I would gladly take back the eczema in exchange for normal bowl movements again.

    Anyway, I figure there is some sort of connection between lipase, eczema, and my bowl issues, but I'm not clear. Some people seem to be saying that eczema is caused by bad bacteria rather than candida, so I‘m a bit confused about what kind of remedies I should be considering. I wonder what would happen if i started taking lipase supplements. Would my skin problems come back?

    Sorry for thinking out loud here. It's all pretty new to me. I live abroad, I‘m kind of stuck figuring this out on my own. I sense that the doctors back home might not be much more helpful however.

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