Of Mice & Men: My Rodent Study Disclaimer

The purpose of this post is to have a sort-of "disclaimer" to link to (if I can remember) whenever I discuss a rodent study here at the Asylum ... A small manifesto if you will, on my feelings on the utility and limitations of rodent studies in relation to human beings.   Also, I look at this post as a way to remind older readers and/or inform newer readers as to my background.  I spent roughly five years in the company of countless rats and mice, working for Big Pharma, and when I speak of rats, I'm not talking about my colleagues ;-)  My job was half analytical chemistry, half metabolism.  I worked on mostly discovery level drug candidates (a level before development) characterizing the absorption, metabolism and routes of excretion of these drugs, mostly antidepressants.  As such I've chopped the heads off of more rats than I care to recollect, opened up countless abdomens of mice to get maximum blood samples from the vena cava, removed/homogenized and analyzed countless livers, brains and intestines, observed behavior of these animals in their cages when dosed with the drugs I was giving them, etc.etc.etc.   As such, I do take somewhat personal affront to those who issue blanket dismissals of any animal studies.  As far as I'm concerned you're all a bunch of hypocrits unless you have never taken anything more than an aspirin and/or never intend to and plan to die a "natural death" feeling full pain and discomfort from whatever might befall you on this journey we call life.  I'm not going to turn this into a defense of Big Pharma, I have no affiliation, and since the days when I worked there (late 80's) I've felt our country is vastly over-medicated (and it has only gotten so so much worse since).  But I mention this because I believe my perspective is a bit unique in this regard.

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Some links about Gut Microflora

This is mostly a bookmarking post to put some links out there.

Same poop, different gut - this one deals mostly with fecal transplants to treat bacterial infections

The gut flora as a forgotten organ - mostly dealing with diseases though touts the promise of obesity relationship

The environment within: how gut microbiota may influence metabolism and body composition - An excellent review of the current understanding of the role of gut flora in inflammation, disease, obesity, etc.  The lead author is the researcher who did the fecal transplant study on obese men that demonstrated improvements in insulin sensitivity (see next link).  I recommend reading this one.  IMO, at this point, finding a bacterial solution to obesity seems to be a long-shot and lots of wishful thinking.  

Fecal Transplant Flushes Insulin Resistance  I really look forward to their upcoming publication of this work.  It will be interesting to see the magnitude of the improvements, if it persisted past 6 weeks (e.g. was there a change in the IR as triglycerides returned to "normal"?), and the long term analysis of the microflora pre & post-transplant.  

I wonder how much of this has less to do with the bacteria and more to do with flushing the gut.  We recycle proteins and lipids in our intestines, and perhaps removing cholesterol and other phospholipids tricks the body into thinking it's in a totally different state of nutrition?  If this is so, one would expect things to return basically to "normal" down the line.  

Of Mice, Men & Microflora II: Microflora & Energy Balance

Mostly based on studies like THIS (abstract only), there's a new whiff in the air around obesity researchers.  Some go so far as to call gut microflora an "unsung organ".  Some have picked up this ball and run with it to the point of making wild claims that microflora control how much energy we extract from our food and we have no control over "energy in".   

Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet.

Firstly, we have correlation here, not causation.

Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'.

Many have read this and jumped all over it to say this indicates the arrow of causation goes from microflora to obesity.   That seems reasonable until one considers what actually happened here.  Germ-free mice are smaller because they lack a major component in extraction of energy from their diet.  I discussed this in Of Mice, Men & Microflora I.  Basically, rodents are hindgut fermenters who rely on fermentation for a significant amount of energy extracted from food.  Their digestive systems are clearly different from the human digestive system.  If you colonize their guts with more bacteria that are efficient energy extractors, is it any surprise the animal gains more weight?  But this does not indicate causality because we do not know the microflora composition of the obese mice before they became obese.  My gut { pun alert } reaction on all this is that a nutrient dense intestine favors the growth of certain bacteria over others, and the direction of causality goes from hypercaloric diet to microflora + obesity.

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Of Mice, Men & Microflora I: The microflora transplant study

A while back I listened to an interview with Steven Guyenet of Whole Health Source blog where he mentioned a study where the gut bacteria were transplanted from obese mice to normal mice that had no endogenous bacteria.  The normal mice gained more weight.  Microflora differences have been identified between normal and obese humans and normal and anorexic humans.   This has led to much speculation that changes in microflora could be a causative agent in obesity.

This is one such study:   An obesity-associated gut microbiome with increased capacity for energy harvest

I look at such studies and consider them to be interesting, but of all the alternate theories out there, I'm probably most skeptical of this one as being a significant cause of obesity.  I'll deal with the energy balance aspects and some related math in future post.   This post will focus on the differences between rodent and human digestion that lead me to believe that the observations in mice may well not translate to humans.

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