Innate immunity and the gut microbial ecosystem

A quick-ish post following the publication of a real fact-finding paper by Larsson and colleagues* (full-text). The aim of the paper was to map out how innate immunity intersects with microbial composition along the length of the gastrointestinal tract in a mouse model.

If you are slightly adverse to mouse research I'm afraid that you won't like this study much, which basically looked at bacterial composition in twelve segments of the mouse gut corresponding to the small intestine, cecum and large intestine correlated with several hundred/thousand genes regulated by the gut microbiota.

I won't lie to you in that this is quite a complicated study to follow. My Mr Men take on it suggested a few important findings were presented:

• In the small intestine, several thousand genes were regulated by bacterial microbiota. By comparison, fewer genes were regulated in the colon than other areas thought to be due to some shielding in that part of the gut from bacterial exposure.
• Depending on whether the authors looked at wild or germ-free mice, there were some interesting differences in different parts of the gut for genes related to lipid and fatty acid metabolism and nutrient absorption and metabolism. Genes governing cholesterol biosynthesis seemed to be top of the pile when it comes to being affected by microbiota as a function of whether or not there was a loss of innate immune signalling (Myd88-deficient). 
• When it came to gut barrier function along various stretches, gut bacteria had some ability to alter the expression of some important genes according to comparisons between germ-free and wide mice. 
• Myd88-deficient mice showed alterations in the types of bacteria present, some signs of disordered antimicrobial resistance as well as being potentially more susceptible to viral infections such as norovirus.

I can't possibly do justice to the amount of data presented in this paper. Extrapolating from the mouse model to humans, this data suggests that we have an extremely important symbiotic relationship going on in our deepest, darkest recesses. A relationship between self and bacteria; where genes and environment seem to play key roles in how we metabolise our food, how we regulate our ability to take on bacteria and viruses, and ultimately how our health in other organs might just want to make reference to the gut also.

* Larsson E. et al. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut. November 2011