2019 Biopsych Seminar Thursdays

            The gut-brain axis is a relatively new discovery, but it has been definitively determined that there is a symbiotic relationship between the trillions of microbes that live in our gut and our own systems. Specifically, there is evidence that large changes in the microbe populations or behavior in our gut can cause changes in the central nervous system and immune system. Symbiotically, changes in the CNS and immune system can also have impacts in our gut. There have been connections determined in a variety of diseases, antibiotic use, and mental illness related to the gut-brain axis. These two papers, by Reber  et al. and Buffington et al.,  use mice to examine the relationship between gut microbes and stress response or behavioral changes.  I first read Buffington et al.  which seemed to be the more easily understood of the two papers. The authors examined if high fat maternal diets (and that effect on gut mictobiomes...

There are hundreds of billions of bacteria living in our guts. Fortunately, our relationship with most of them is symbiotic. Specifically, bacteria in our gut can affect our nervous and immune systems, and our brains can affect the balance of microbiomes. This relationship is referred to as the brain-gut axis. Reber et al. (2016) and Buffington et al. (2016) are two studies investigating “good” bacteria in the brain-gut axis and its role in stress, and social and synaptic deficits, respectively. Featured in the paper by Reber et al., M. vaccae, bacteria found naturally in the environment was heat-killed and administered in a vaccine to mice. Researchers found that in response to stress, this vaccine promoted proactive coping behaviors, more resilience to stress, and reduced colon inflammation, compared to unvaccinated mice. The authors also point to the “old friends” hypothesis, which claims that modern day hygiene has prevented humans from being exposed to environmental organisms th...

I found that both papers brought valuable insight to our understanding of the gut-brain axis. Reber et. al showed that administration of heated Mycobacterium Vaccae induced behavioral changes associated with decreased stress response, measured by EPM, and linked these findings with associated prevention of stress induced decrease of slc6a4 and tph2 mRNA expression in the dorsal raphe nucleus (seretonin bioavailability), as well as preventive effects in colon tissue damage in acute colitis. Since glucocorticoids have been shown to increase bacterial adhesion and transition into lymph nodes, the mitigation of stress induced inflammatory changes in the gut by M. Vaccae make it a potent target for therapeutic modulation of pathobionts. I hypothesize that the presence of this probiotic induces anti-inflammatory effects not only via TGF-B signaling and Il-10 cytokine release, but also direct microbiota to microbiota communication mechanisms preventing aggravation of potential pathobionts ...

Reber et al.’s and Buffington et al.’s articles both explore a lesser-known area of research on psychiatric disorders: effects of the microbiome. However, I found Reber et al. to be more interesting and relevant to courses I’ve taken in the past. The study mentions the hypothesis that a lack of immunoregulation can contribute to increased stress-related and chronic inflammatory disorders in high-income countries. This is partially due to a lack of contact with microorganisms with which humans co-evolved. Homeostasis of the microbiome can be further altered by stressful experiences. Research has shown that probiotic treatment can have antidepressant-like or anti-inflammatory effects in animals, although it’s unclear if these effects are due to their immunoregulatory properties or their ability to prevent stress-induced diseases. Therefore, this study studied the effects of Mycobacterium vaccae on behavior and spontaneous colitis in stressed mice. Immunization had numerous effects. T...

This week we focused on two examples of research highlighting the effects of environmental differences on gut microbiota and its downstream effects on brain function and behavior. Reber and colleagues (2016) used the chronic subordinate stress to explore the effect of stress of gut microbiome and the protective role m.vaccae immunization in those alteration. Results demonstrated that m.vaccae had a protective effect to CSC induced changes in coping response, increased anxiety-like behavior, reduced serotonin expression and reduced microglial density. M.vaccae also prevented colitis resulting from stress. The protective effects of m.vaccae in anxiety-like behavior and colitis were dependent on Treg. The CSC model is especially relevant for disorders like PTSD, which are stress induced, and this research demonstrates that m.vaccae immunization protects again some stress-induced changes in both behavior and neural dynamics. The parallel is not as clear when it comes to the compromised i...

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-regulato...

This week, the papers focused on the relationship between the gut microbiome and the brain, known as the gut-brain axis as potential risk factors for stress related psychological disorders and neurodevelopmental disorders. Buffington et al found that offspring of mice who were fed high fat diets during pregnancy (MHFD) had social behavior deficits, repetitive behaviors and anxiety which are all ASD associated behaviors. The deficits in social behavior were directly related to dysbiosis of the MHFD gut, specifically the absence of lactobacillus reuteri (L.reuteri) accounted for this phenotype. What I found to be the most interesting result was that when L.reuteri was given through drinking water the MHFD social deficits were restored however their anxious and repetitive behavior were not remedied. This made me think about the MHFD model and its potential relation to the Reber et al paper. Could the microbiome dysregulation and more specifically the lack of L.reuteri ...

I really enjoyed learning about an area of neuroscience and microbiology that I don’t typically read about. The interaction between gut and brain has definitely been a hot topic in the last few years, and it’s exciting to see robust research published linking the two in development and manifestation of psychological disorders. At my last co-op, we started to work on a mouse model of Parkinson’s disease in which pathology-inducing alpha-synuclein is injected peripherally and travels (presumably via the vagus nerve) to the midbrain and cortex! This is in the context of findings that alpha synuclein aggregates can originate in the gut and induce aggregation in the cortex and midbrain. I found the Buffington et al. paper much easier to follow and digest (no pun intended), and that’s likely at least in part why I preferred this one to the Reber et al. paper. The use of heat-killed bacteria was a great way to delineate vagus /gut interactions from immune response to the bacteria. It’s ...