Monday, April 22, 2013

Getting Schooled

In my continuing blog series, (Mis)adventures in Microbiology, I want to share the next leg of my journey into understanding the critters living on and within us.  I promise, this is related to allergy, so bear with me while I convince you that yes, there is a definite reason behind this microbiology madness.  You are reading an allergy blog, after all!

As the title implies, I'm getting schooled!  For the Spring term, I signed up for a course in Microbiology, which means I'm sharing a classroom with some of the very students I could have taught anatomy and physiology to in previous terms! 
It totally wigs my fellow students out when they ask, "So, what do you want to be...", only for me to fire back with, "Well, actually, I'm an instructor."  After the initial shock wears off, most think it's cool, but I swear I've gotten a few stink eyes, since they probably think I might ruin the curve or something silly like that.  They should have no fear, though, because I humbly admit I am clueless about microbial lifeforms.  The last time I took a course in microbiology was as an undergraduate student over 10 years ago, and I swear, I don't remember a darn thing!  I supposedly got an 'A' in the course, but clearly my interests were elsewhere... like brains and creatures with a backbone?  Microbes don't really have brains like 'us,' so I relegated that information to the category of, oh that's interesting... and didn't give it a second thought once I turned in that my final exam over 10 years ago.  How important could microbes really be, other than occasionally giving me an obnoxious case of strep throat for which I could go the the doctor and receive a full course of microbe killing pharmaceuticals.  Take that! - stupid creatures without a brain... 
Petri Dish

Ah, but my haughty attitude is crumbling before me.  Reason #1 is that I am on a quest to understand the human immune system - how does it work and what happens when something malfunctions, such as in allergy or autoimmune disorders.  It's almost painful to admit this, but as I've started out on this journey of understanding, my entire world has centered around what happens in a malfunctioning human immune system.  Yes, I know what the damn immune system is supposed to do (protect us from pathogens), but somehow I thought that the disease mechanisms were entirely a malfunction of the human.  Over time, narrow-minded me has realized that in order to understand a malfunctioning human immune system, I have to understand a properly functioning immune system.  And in order to understand a properly functioning immune system, I have to understand the very things the immune system is designed to protect us from.  Mmm, hmm... those "meaningless" microbes that I completely disregarded due to their lack of advanced computational prowess all encased in a pretty cranial package.  Perhaps there is a reason after all for why one of the National Institutes of Health, The National Institute of Allergy and Infectious Diseases, lumps 'allergy' together with 'infectious disease.'  I kid you not, I was mystified for a long time why these two things were part of the same institute!

More interesting, however, is Reason #2 for my new-found respect of the microbial world.  As I've mentioned before, I am absolutely smitten by all the fervor surrounding the critters on and within our bodies, and what it all means for human health and disease (for a nice primer on the human microbiome, please see Michael Specter's article in the New Yorker "Germs are Us").  

The game-changer for me (hence why I'm in a Microbiology class), was an article published in the Journal of Allergy and Clinical Immunology this past January - "A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis."  I'll just preface that this article is a doozy to get through and I wouldn't be surprised if this went straight over the heads of many allergists.  The studies in this article are dense with complex jargon and there is a LOT going on experimentally.

Here is a very simplified, general summary - a special strain of mouse (genetically susceptible through an IL-4 receptor mutation) that is anaphylactic to "egg" was found to harbor a significantly different microbial community in their guts than mice who do not develop an "egg" allergy in spite of the best efforts of the researchers to sensitize these poor mice to "egg" (These are called "wild-type" mice, who lack the genetic "predisposition").  This finding is interesting on its own, but it gets even better.  It turns out you can "infect" wild-type, germ-free mice (i.e. mice that are born and raised in the absence of microbes) with the microbial critters from the "poo" of mutant "egg" anaphylactic mice, and BAM! - these normal mice, who could not be sensitized to "egg" for the life of the researchers, suddenly experience anaphylaxis to "egg."

There is much more complexity to the research, but the overall conclusion is that there is likely a very complex interplay between our genes, immune system, and gut microbes that may determine food allergy.  These results imply that certain communities of gut microbes (not just the individual microbes themselves) may in fact be pathogenic - causative agents of food allergy.  The results also imply that our genes likely influence the community of gut microbes that get established in the first place.

The one glaring question at the end (for me, anyway!) - did the researchers try to "infect" the mutant "egg" anaphylactic mice with the "wild-type" microbes?  Could these genetically susceptible, "egg" allergic mice tolerate "egg" following new microbial gut flora?

This is definitely a leap over a giant chasm in our scientific understanding, but if these results hold, could it be possible to reverse food allergy in humans by "wiping" pathogenic gut microbial communities and replacing them with microbial communities known for "tolerance?"  We have so much to understand yet, but at least it's a start.

Interesting!  Nonetheless, my journey into taking Microbiology has already helped in parsing through this very dense paper, and understanding why the researchers performed certain methods the way that they did. 

To all the microbes out there - you have my utmost respect.  I acknowledge that my body is not my own, but rather an amalgamation of one part me and many parts you.  What's mine is yours if you promise to play nice :). 



  1. I missed this post, but it's fascinating! In one of our ongoing studies, we've found significant differences in the gut microbiome due to non-food related environmental alterations. It's fascinating to think of all of the seemingly unrelated things that could affect our immune system and our little symbiotic microbe friends!

    1. Thanks for you note, kcat! I'm continually amazed on a daily basis. The emerging complexity is mind-boggling. I'd always be up for hearing more about your line of research, so feel free to shoot me an email if you'd like! It's under contact. May the lab gods be ever in your favor!