Friday, 25 November 2011

Gut bacteria and the immune system

Quite an interesting article by Lamous√©-Smith and colleagues* has appeared on the potential gut bacterial requirements of the immune system. The paper is open-access so readers are invited to read it at their leisure.

The basic conclusion reached from this research is that the ability of a mouse (and by proxy a human being) to mount an immune response to a specific pathogen (bacterial or viral) might be to some degree affected by the presence/absence of certain gut bacteria.

In the case of this paper, researchers undertook investigations based on two different scenarios: (a) a mouse model where antibiotics were used to disrupt the normal gastrointestinal (GI) flora and (b) a germ-free mouse model who were subsequently colonised. Under such models, mice were injected with a suspension of ovalbumin (the main protein in egg white) and an immunity stimulator, Freund's complete adjuvant. The authors then looked at the mice ability to mount an immune response to the egg white protein (ova).

They noted a few interesting observations:

  • Administration of antibiotics lead to some interesting changes in the gut microbiota. I should perhaps mention that pregnant mice were given antibiotics in their feed so the changes were noted in both mother and baby mice when born. The specific combination of antibiotics given to pregnant dams - ampicillin, streptomycin and clindamycin -  seemed to particularly deplete Firmicutes and Bacteroidetes bacterial species leaving Enterobacteriaceae to dominate. I don't like the idea of labelling bacterial species as good guys or bad guys because that is a little generalised and unfair. Having said that the Enterobacteriaceae includes things like Salmonella, E.coli, Klebsiella and few more 'pathogenic' species among their lot; if they were people, these would be the ones not to hang around with. 
  • Those offspring mice born to mothers on antibiotics seemed to show similar changes to gut flora. Additionally, antibody titer levels to ovalbumin were lower in this group when compared to a non-antibiotic exposed group when immunised at 7 days. These findings were not replicated when injected at 14 days.
  • Looking at the second mouse model where gut flora was absent, the authors reported consistently lower titer levels across age and when injections were given. This finding was kinda confirmed when germ-free mice (those with no bacterial flora) were colonised via bacteria derived from normal gut flora mice (I guess a sort of bacterial transplant!) thereafter more appropriate antibody titer levels were noted .

Appreciating that these experiments were carried out on mice and quite a small group of mice, there are some interesting things to take from this research. Already on this blog discussions have ranged from gut bacteria and a possible link to coeliac disease to the potential usefulness of bacterial transplantation for certain bowel conditions. Within these pretty diverse areas, a common theme is a potential role for the immune system in terms of clinical outcomes. What this research adds quite nicely, is that our ability to fight infection, develop immunity might be quite a bit more complex than previously thought. Our gut bacteria potentially being a mediator of immunity.

Thinking back to some findings in that other field of interest to me, autism, I do wonder about the implications of this research. On a sister blog, I recently discussed a paper looking at carbohydrate metabolism and dysbiosis in cases of autism. One of the findings from that small-ish study was that levels of Bacteroidetes were in shorter supply. Coincidence or perhaps tied into some interesting data on antibiotic use? Given the various studies suggestive of problems with immunity at least in some people with autism, I wonder if we should be looking at the gut bacteria/immune system relationship a little more closely?

Of course it easy for me to sit here and speculate, compare and contrast. Precisely how our bodies make and utilise immunity is still a source of much research and investigation.

* Lamous√©-Smith ES. et al. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS ONE. NOvember 2011

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