Microbiotic effects on stress and social behavior in mice- Sierra Smith


For the final week of paper discussions, we dove into the fascinating and very new topic of the gut microbiome, and the influence of microbiotic composition on mice either under chronic subordinate colony housing situations or the offspring of dames fed a high-fat diet. In the first paper I read, Reber et al, there were fascinating findings that although supplementation with heat-killed Mycobacterium vaccae did not prevent all microbiotic changes induced by stressful housing conditions, it did have a significantly protective effect on the development of spontaneous colitis and stress-induced aggravation of pre-existing inflammatory bowel disease (colitis in mice). There was also a profound effect on proactive defensive behaviors in mice housed in CSC conditions, whereas they became defeated less easily and displayed significantly more proactive behaviors when faced with an aggressor. I was particularly excited to read about the increased Iba1 immunostaining in fear-regulatory areas of the prelimbic medial prefrontal cortex, as I spent much of my last co-op examining Iba1 microglial staining patterns in the inflammatory brains of a mucolipidosis type-4 mouse model.
Although I loved reading the Reber et al paper, I had the strongest reaction to the following paper I read, Buffington et al. I had previously heard about the relationship between gut microbiome and autism spectrum disorders in humans, but I had not read anything evidenced in mouse models like this paper demonstrated. I was particularly shocked by the finding that treatment with a specific gut bacteria, L. reuteri, found to be deficient in the offspring of high-fat diet mothers, actually rescued the observed social impairments in the offspring without L. reuteri treatment. The Buffington group was actually even able to identify a critical period for fecal transfer including L. reuteri at 4 weeks of age. At the same time, the Buffington group was able to also show that L. reuteri has no adverse effects on the offspring of mice that were fed a normal diet and who have no deficiencies in gut microbiome. I think this is an absolutely incredible result because it means that if the same principles apply in humans, it is possible to produce a supplement containing L. reuteri to overweight mothers who have a greater risk of having children with ASD-related disorders without any adverse effect on children who would otherwise not go on to develop an ASD-related disorder.
One thing I was slightly skeptical about also was how good of a model the high-fat diet dames are for ASD-related disorders in humans, as there are so many factors, both genetic and environmental, that play a role in children developing autism. I’m wondering if, since the Buffington group saw significant effects of maternal diet alone on the social behavior of the offspring, this is too profound an effect to account for the relatively small numbers of autism diagnoses made even within higher risk groups. All in all, these two papers absolutely fascinated me and I thoroughly enjoyed the opportunity to read them for the last week of paper discussions.

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