Brain Gut Interaction

I was very interested in going into this week's papers as through my time as a BNS student I have not encountered anything to do with the gut microbiome or the brain gut interaction. Reber et al. 2016 provided an expansive look at the effects of bacterial immunization on stress resilience in mice. However, I felt as though I left the paper with more questions than when I began reading it. Although they showed various ways in which the mice housed under the chronic stress paradigm improved in terms of proactive coping and decreased stress induced colitis, they also glazed over many behavioral paradigms looking at stress and anxiety that did not show consistent results. The connection of immunization using heat killed M. vaccae was also used to study the effects on microglia and the serotonergic system. Although this provides insight to how the effect of immunization can be used as a therapeutic or preventative measure, there was no real rhyme or reason as to why they looked at these CNS elements in particular. The tests and results seemed very disjointed from one another with no clear link or correlation between any of them. It more or less looked like a data dump with research going down as many routes as possible with this immunization hypothesis. I would have liked to have seen an in depth analysis of one of these projections as opposed to this many hypotheses and conclusions mostly being supported by previous research and not their own. 

I do think the idea of decreased variety of bacteria living in our gut, due to modernization of living style leading to less exposure to varied microbiomes, is a very prevalent issue. And it is a major cause for the increase in immune and inflammatory diseases, however I do not think their methods that the authors used were very cohesive. Another point of contention, for me, was the idea of exposure to heat killed bacteria acting as an “immunization”. This idea lends itself to thinking of it as exposure leading to immunity to the bacteria, when in fact this bacteria is necessary and causing internal transcriptional changes that are not necessarily part of the innate or adaptive immune system. Immunization is generally thought of as exposure to increase antibody production and promoting quicker immune response, however this is not the definition the paper used. Although the exposure to M. vaccae induced stress protective effects and dependence on Treg, which is related to immunity, the results differed depending on whether they were looking at anxiety effects or mRNA regulation indicating that some of the effects are not even dependent on the T cell mediated immune pathway. I also do see the brain gut interaction given their data on the effect of this bacteria on the serotonergic system and testosterone effects. This could have been expanded upon in their paper. My confusion may lie in my lack of experience with brain- gut interaction research, but I would have liked to have seen independent papers each following one of the hypotheses mentioned. 

Buffington et al. 2016 were much more convincing in their approach to studying the brain gut interaction and the effect of bacterial exposure to socially deficient offspring of mothers exposed to a High Fat Diet. The most compelling results from the paper was the ability to reverse social deficits induced by the high fat diet using exposure to mice reared with mothers on normal diet and the selective addiction of the L. reuteri bacteria. This data was robust and incredibly displayed. Taking this further they compared the effects of L. reuteri with intranasal oxytocin administration and found the effects on LTP to be quite similar. This opens the doors for therapeutics and prebiotic cocktails that would allow for both therapeutic and preventive measures of disorders such as ASD. Given that a lot of prebiotic concoctions already exist for human consumption and already existing intranasal oxytocin experiments, this would be an easy transfer to human research. One thing in this paper that was completely novel to me and quite fascinating was the idea of Germ Free mice. I did not know that it was physically possible to rear mice that did not contain any environmentally provided influence (in terms of the microbiome). This was quite astounding to me as it is hard to believe that these organisms are viable till reproductive age. This model allowed them to further test their hypothesis of missing microbes leading to social deficits. One thing that stood out to me about both papers was the use of heat killed vs live bacteria and the results from Buffington et al. that showed no changes upon heat killed L. reuteri administration. I wonder what the difference is here and why with one experiment heat killed seemed to have made a difference and in the other not? This is something I think both teams should have addressed and presented reasoning for.