Buffington et al. and Reber et al.: Gut-Brain Interactions

While I have not encountered a lot of gut-brain interaction literature yet. I found each paper unique and fascinating. Reber et al felt inaccessible for me. I felt like I didn’t understand what the goal of the paper really was and why they did the tests that they did. It seems like most of their relevant information got shoved into numerous supplementary figures and their behavior was quite difficult to follow. Multiple sections of their paper were supported with data found entirely in supplementary figures, which makes it difficult to follow the same conclusions.

I have a few issues with the behavior they chose and because of this, I struggle to find driving conclusions from their work. I don’t understand why the CSC was not only the prior stressor but was also the acute stress condition both groups faced. To me, I feel like it would have made more sense to have the CSC be the prior stressor and then judge the effect on social behavior with maybe a three choice chamber test or test novelty interaction in some other way. For me, I’m just confused because half of their cohorts already experience that stressor on a daily basis and it’s what they live with, so I don’t really feel much validity from their behavioral output because the SHC groups are the only groups experiencing a novel behavioral paradigm. I think this is most evident with the trends of the first figure. There is no variability in the CSC group in the actual tests of CSC and it seems like the SHC group trends to the same pattern as the CSC which would indicate habituation of the animals. I don’t know why they didn’t do a social defeat paradigm instead. I didn’t particularly enjoy this behavioral paradigm and it seems incredibly long and was quite confusing to read about in the paper because of the negative days in addition to the positive days. They based the rest of their investigation on these reports, but I struggle to see their validity given the complexity of their paradigm and the seeming habituation of their animals that was never addressed.

Additionally, I found a lot of issues with their conclusions stemming from IBM and utilizing the M. vaccae immunization as a potential therapeutic intervention. They start by stating that anxiety and depression are more common in patients of IBM. They go on to imply that this is due to gut-imbalances. I feel that is a wildly narrow view of IBM and the effect the disease has on social health. I feel that a larger reason for the increase in anxiety and depression could be linked to the social ramifications of a disease like IBM. Shame and embarrassment are two huge emotions that can drive behavior and a lack of proper social standing and the potential for embarrassing situations would play into the development of those disorders. 

Further, they conclude that “immunization with M. vaccae may be useful in the prevention of chronic stress/repeated trauma-induced inflammation and subsequent development of somatic and mental disorders”. This to me feels like an over-stepping in translational conclusions. This is implying that giving someone probiotics or another form of bacterial immunization could just irradicate or prevent a mental disorder from developing. This does not take into consideration the large and very important role that psychosocial development and maintenance play in mental disorders. It feels irresponsible to come to that conclusion without really strong and really valid behavioral data to support so. This conclusion could instead feed into the negative stigma of mental illness. Not to discredit the potential positive effects of focusing on treating the microbiome can have on mental health, but it just seems a little unfounded of a claim in this paper. I could very easily see this sentiment be reduced down by pop-psychology to mean that “you could have prevented your mental illness from eating a healthy and diverse diet that includes probiotics”. I know it may seem extreme, but that conclusion just rubbed me the wrong way. 

I did enjoy the Buffington et al paper a lot more though. Their behavior was clean and clearly defined and visually represented well. There was a logical foundation for their research that lead had a logical path of progression that ultimately determined that obesity in mothers can cause social and behavioral deficits that can be ameliorated by treatment with deficient bacteria. The study focused specifically on L. reuteri and it’s specific role in social behaviors. And they focused on this bacteria from sequencing data done on their offspring. Overall, the paper found a relevant issue in humans with a rise in obesity and an increased risk-factor of ASD in their offspring. I found it fascinating that they were able to link this to oxytocin and find a potential neural mechanism where this bacteria could be affecting neural output and function. Finding the changes in oxytocin positive cells in PVN was intriguing. Additionally, their work with GF was incredible. Working GF mice is no easy or cheap process, and I think their ability to recover social deficits with fecal transplants is amazing. This to me is a stronger foundation for the idea that treating the gut-brain axis can be useful in treating mental disorders. That by giving mice a new “healthy and diverse” microbiome, we can positively affect their behavior. I think it would be fascinating to look at the generational effect of this phenomenon and to see how far-reaching this social deficit can be seen and to see if there are potential gene regulation or accessibility changes that could be linked to any long-term generational effect.

They also only claim that probiotics could be used to affect specific social behaviors or be used as a non-invasive treatment for those with ASD, not preventing it. I think the key here is non-invasive treatments that could potentially be dietary additions. While I don’t know much about drug compliance in ASD patients, having positive effects from probiotic-rich foods could be an easier way to treat the complex disorder in addition to other treatments. I do think though probiotic treatment does not take into consideration the economic disparities of at-risk populations. One of the easiest ways to deliver probiotics into someone is through probiotic-rich foods like keifer, kombucha, sauerkraut, kimchi, tempeh, etc.. I do feel that there is a huge consideration on translational impact of this research that’s should be considered. I think analysis considering the socio-economic link to an increase in obesity and lack of gut diversity is vital to truly understand how translational this research can be is. With this in mind, these populations at risk for obesity might not have access to healthier foods or other avenues that could introduce these beneficial probiotics. Obesity specifically is not a single-faced issue linked only to a lack of personal motivation or drive. While I don’t think this discounts the research, it is important to consider that a huge population affected by mental illness are those of poor social and economic standing who barely have access to any form of adequate mental health care. Perhaps I am considering this more with these papers because when I think of probiotics I think of expensive grocery stores and pretentious groups of people that are predominantly white. It does seem simple, the addition of probiotics to benefit mental health, but it reminds me that accessibility is still a major issue in the mental health care field.