Week 9

The timing of this week’s papers couldn’t have been more perfect. For the last couple of weeks, I have been extensively researching the role of gut microbiota and its implications in anxiety-related disorders and depression for my literature review in another class. I truly believe that gut microbiota should be considered as an alternative paradigm for investigating neuropsychiatric disorders. The ability of these tiny microorganisms to influence brain development and behavior is so incredible! 

The Buffington paper was really well crafted and easy to read. It was surprising to see no significant difference in offspring weight between groups. One would expect MHFD offspring to be heavier considering how obesity also has a genetic link and offspring from obese parents tend to be on the heavier side. But I’m not sure if the mother rats in this experiment were physically obese or not. The finding that “GF mice that received fecal microbiota from MRD offspring at weaning 4 weeks, but not at 8 weeks showed normal social behavior” is not that surprising because gut microbiota influences function at different developmental time periods. I remember reading another paper that highlighted this critical time window - where adult rats were administered with antibiotic treatment for 6 weeks and this sustained depletion resulted in increased immobility and decreased swimming behavior in the FST (depressive-like behavior), which was further supported by a decrease in serotonin levels in the hippocampus. However, no effect was observed in the anxiety in the OFT or EPM, suggesting critical windows during development for microbial influence over anxiety circuits [1]. Another cool thing about this paper and gut microbiota in general is that a simple change in the composition of bacteria can have such vast negative or positive effects. For example, dysbiosis in L. reuteri composition led to social deficits and this could be reversed simply by treatment with the same. Another cool paper that I read showed that when GF mice were treated with “depression bacteria” collected from non-medicated MDD patients, they displayed depression-like behaviors evidenced by increased immobility time in the FST and TST as compared to controls [2]. It is crazy to see how specific the gut microbiome is and how well it interacts with the host to keep it healthy.

As for the Reber et al. paper, I found it difficult to read, perhaps because they focused on too many different kinds of bacterial species. However, the main effect that they found is pretty outstanding, especially the result wherein immunization with M. vaccae increased microglial density in the prelimbic part of the medial PFC. This highlights how gut microbiota could potentially be a therapeutic target. Out of all the papers we have read, I believe these two are the most promising because transient alterations in the gut microbiota through antibiotic treatment or consumption of probiotics, are activities that humans actively engage in, therefore the results are more likely to be translatable.

1.     Hoban AE, Moloney RD, Golubeva A V., McVey Neufeld KA, O’Sullivan O, Patterson E, Stanton C, Dinan TG, Clarke G, Cryan JF: Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat. Neuroscience 2016, 339:463–477.

2.     Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X, Zeng L, Chen J, Fan S, Du X, et al.: Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol. Psychiatry 2016, doi:10.1038/mp.2016.44.