Brain - Gut Microbiome Interactions

The gut-brain-axis is starting to be more and more explored within the scientific literature for psychiatric illness. Reber et al examines the strand of bacterium M. vaccae and its effects on a stressed mouse model. To do this, they used either a chronic subordinate colony housing (CSC) or single housed control (SHC) paradigm with mice that were either injected with a heat killed M. vaccae which acted like an immunization, or vehicle. Their results included an analysis of  behavior, behavioral tests (open arm maze, light dark box, open field test, etc), microglia analysis, microbiome sequencing, Treg measures, and more. Ultimately, the study concluded that M. vaccae immunization led to proactive coping, a reduced stress response, less time in a subordinate position for mice, and reduced inflammation. I think this article highlights many benefits to a strong microbiome, however, it is only looking at one specific bacterium. I would like to see many of these measures repeated with many different bacteria. Additionally, I found it interesting that of all of the behavioral tests they did, only the elevated plus maze had significant results. While it can be difficult to measure anxiety of psychological states, if two tests are supposedly measuring the same or similar thing, I would expect to see similar results throughout the test. I wonder why it was just the elevated plus maze that showed significant results of increased anxiety in the mice without M. vaccae? Overall, I think that the microbiome, while it may not be ready as a clinical treatment for PTSD or anxiety anytime soon, can help support a healthy brain development via its connection with the vagus nerve and more. I think this article highlighted the many potential benefits of immunization, and that early exposure could prove beneficial to many individuals. I am still a bit confused on the specific role of immunization and the gut microbiome and how they are different.

Buffington et al also examined the gut brain axis with a specific focus on the offspring of mothers with a high fat diet (HFD). Initially, the offspring exhibit more antisocial behaviors and have a different/less microbiome. However, if they are housed with regular diet offspring, both their microbiome and antisocial behavior are corrected. While this definitely points to the microbiome playing a role in behavior and vice versa, I am very interested in how the change was translated or initiated from the regular mice to the MHFD offspring. Next, they examined germ-free (GF) mice and determined that a fecal transplant was only most effective at ameliorative social deficits within a certain time frame, suggesting that there is a neurodevelopment window in which the gut could exert its effects. They also examined the bacteria’s influence on oxytocin using  L. reuteri. This was very interesting to me because oxytocin has been used a lot in autism research, and the idea that this can be manipulated using a gut bacteria is incredible. Treatment with L. reuteri in the drinking water significantly improved social behavior in the MHFD offspring, which had originally had less oxytocin in the reward system. Overall, I thought that this article was extremely interesting and did a great job of tying the behavior together with the bacterial changes. Additionally, the idea that oxytocin can be replenished by a bacterial colony is exciting and could lead to future treatments. That being said, mouse models of autism are still very different from the human equivalent. While the researchers looked at social, repetitive, and anxiety like behaviors, it does not necessarily match with human autism. Additionally, autism is a spectrum, which can be hard to model in rodents. Still, I think that this article gives great insights into the gut and social behaviors in general. I am still very interested in how housing with the regular diet offspring was able to rescue both the microbiota and the social behaviors. I am also curious about the effects of too much or a ‘good’ bacteria; while we see that these amounts are beneficial, I think it is important to consider that there may be a tipping point and be aware of that if we are to introduce this clinically. Overally, it is obvious from these articles that the gut and brain are linked, and more research needs to be done into their connection and potential health and therapeutic benefits.