Thursday, March 23, 2017

Buffington & Reber

I was excited to read these papers this week because my only introduction to the idea of the intestinal microbiome-host interaction was a podcast on NPR’s Science Friday years ago – on the episode, they discussed something to the effect of a study exploring the possible effect of shifting gut microbiota populations on the human serotonin systems. I don’t remember the details of the study, but the concept of fecal transfer definitely stayed with me.

The Buffington paper was blissfully straightforward. At first, I had some questions about the validity of deficient social interactions as a model of ASD-like disorder, as deficient social interaction could easily be associated with basic things like anxiety or disorientation. However, I was excited to see later in the paper that the MHFD offspring mice were also displaying repetitive and perseverant behaviors. Despite these behaviors not responding to re-introduction of L. reuteri, I was more convinced that the effects of the shifted gut microbiota of the subject mice were analogous to a disorder such as autism. I found the study’s design to be methodical, although I was confused by the difference between weighted and unweighted UniFrac distances. There were moments in the paper that I felt needed clarifying – one such moment was in the section discussing oxytocin levels in the hypothalamus of MHFD offspring: when making the distinction that the “reduction in oxytocin immunoreactivity was not due to an overall decrease in PVN neurons, since the total number of neurons was unchanged,” does the author mean to imply that the mechanism of signaling between the bacteria and the PVN is via an oxytocin-producing transcription factor? Or that the critical time point of development during which a MHFD-induced microbiome affects cell type during proliferation? Additionally, since I am inept when it comes to interpreting neurophysiological graphics, I wish there had been a better figure legend describing the AMPA/NMDA ratios in the section discussing LTP in the VTA.

Overall, I am comfortable with and fascinated by the Buffington paper’s allusion to oxytocin as the mediator of LTP in the VTA, causing dopamine circuits to be upregulated with social interaction. I hope that soon we will be able to know the mechanism by which the microbiome signals and causes change in the brain.

I found the Reber paper more difficult to understand, as it was less concise and dealt more with the system of inflammation and T cells with which I should have been more familiar. I also had trouble, at first, understanding the idea of “proactive coping mechanisms” vs “reactive coping mechanisms”, since it seemed like “proactive coping mechanisms” actually meant “acts of confidence” (for lack of better phrasing). On a small note, I found it interesting that this research group found success using heat-killed bacteria, whereas the Buffington research experienced distinct failure when taking this approach. I do understand that many bacterial vaccines are inactivated in such a way, but I wonder why there is an observed functional difference. All things considered, I’m fairly convinced by the Reber paper, despite some confusion about their seemingly inconsistent results within the CSC and EPM paradigms after treatment.

I’m sad I won’t be able to attend the make-up class – I loved reading both of these papers. I constantly find myself musing at the possibility that certain types of food cravings could be born out of need from the gut microbiome instead of the body itself, and clearly, the microbiome’s “voice” is much more far-reaching.

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