Friday, September 21, 2007

Commensals


So in an effort to generate some discussion of a topic I've been interested in for a while but am too busy right now (writing grant applications) to get into details... I'll throw this out there and see what happens.

Commensal microbes are generally overlooked but likely have a greater influence on our biology than the pathogenic microbes that get all the attention (and research bucks!).

Topics:
- role of commensal gut flora in obesity
- commensal viruses such as Torque Teno and the dozens (hundreds?) of papillomaviruses that can be isolated from everyone's skin... no warts, no pathology
- recent recognition that an ongoing herpes virus infection significantly impacts on the ability of mice to fight bacterial infections... raises worrying proposition that studying the immune system of "pathogen-free" mice may be as misleading as studying muscle function in a quadroplegic...
- should we devote more funding to these microbes? with limited funds should we tackle the problems (HIV, TB, malaria) or should we (also) study commensal microbes which have (likely) figured out our immune system and could probably teach us a thing or two... thi is actualy the topic I've assigned in the undergrad virology course I teach...

So... very little content... just the nidus of a (hopefully) fruitful discussion/discourse...


8 comments:

Bayman said...

Ha! Finally a real post and something interesting to rescue me from bank-induced depression...

rob said...

"http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050177&ct=1">This article recently published in PLoS Biology is the most interesting thing I have heard of in this vien. Basically after birth the sterile human gut is colonized by microbiota and due to environmental differences this is different from infant to infant. 'A chaotic colonization', I believe the paper calls it. Over time this flora converges on the flora contained in the adult, although smaller differences persist. Perhaps some of the earlier colonization events strongly influence the developing immune system?

rob said...

Wow those are HTML skillz. Thank goodness we use blogger or I would look like an idiot.
Here is the paper I was talking about.

Bayman said...

This might be a bit of a stretch, but I always found it interesting that lactose is digested much better when ingested in yogurt than in milk or other dairy products. This is thought to be a result of enhanced lactose digestion by bacterial B-galactosidase in the yogurt culture. I wonder if bacteria ingested in yogurt could have any overall impact on the constitution of the gut flora? If so, does the consumption of certain bacteria contained in yogurt therefore have any effect on susceptibility to infection or other aspects of health?
What about the effects of any bacteria contained in unpasteurized human or animal milk? (ie acidophillus)?

What happens if you raise lab animals on unpasteurized cows milk or yogurt and then challenge them with pathogens as adults?

Paper

kamel said...

Are we convinced that "commensal microbes" are, in fact, commensal? I guess not, since we're talking about them potentially having a large impact on our biology. Still, it's an interesting topic.

I've blogged before about obesity-causing viruses, that would probably have been identified as commensals before the discovery. The idea that gut flora populations can influence obesity raises a question of cause and effect. Is gastrointestinal bacteria in some way responsible for the fattening of the population, or is the diet of a fast food nation providing a fertile breeding ground for certain types of flora? In mice, at least, the answer is that 'germ free' mice are leaner than their 'microflora colonized' brethren, and when inoculated with microbiota from these conventionally raised mice they see a body fat increase. And of course we know of other ways in which gut flora behaves in a symbiotic, rather than commensal way, such as vitamin K production. Rob recently wrote a post about symbiotic gut bacteria, which of course doesn't rule out the possibility of commensal populations in there as well. Maybe the human microbiome project will provide the answer.

The funding question is a good one also. In an ideal world the money is there to fund both types of research and commensals would get their due. We might find that many of these 'commensals' aren't so neutral after all. On the other hand, trying to convince a granting agency to fund a study on a true commensal - one that has no significant harmful or helpful biological effect - might be a tad difficult, except perhaps in ARW's scenario of learning how they escape the immune system to understand it better. Of course in any funding situation you're eventually faced with a question of "Why fund 'A' when so many more people are dying of 'B'?"

Anonymous said...

I've always been fascinated by the fact that we can recognize and respond to invading pathogens very rapidly, while we "ignore" all the commensal bacteria living in our bodies (even though our body is actually made up of more bacterial cells by #). We don't have a good understanding of how our innate immune system makes the distinction, though I came across this paper, which suggests that innate immune signaling on intestinal epithelial cells differs if a bacterial product is recognized on the basolateral surface (recognizing "bad" bacteria) vs the apical ("good" bacteria) surface.

kamel said...

Anonymous,
Cool paper, and you certainly showed up Rob with your superior HTML skillz.

Bayman said...

Interesting paper, raises the issue of environmental specificity, that studying immune evasion by commensals that live in the gut for example is not be relevant to understanding TB or HIV. The best model for such diseases then might instead be commensals that live in the lung or genitourinary tract. Can any one think of any such model pathogens?

Seems it would be very useful to study a retrovirus that infects us but does not cause immunopathogenesis, although surely someone must already be doing this? SIV would be an example I guess but requires cumbersome study in primates - are there any such human or mouse pathogens under study?