Mental illness and the microbiome - Dana Walker


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. The researchers first observed decreased submissive and avoidance behaviors for mice in chronic subordinate colony housing. These mice also showed increased production of tph2 in the rostral dorsal raphe nucleus, as well as prevention of a stress-induced decrease in slc6a4. Immunization also increased microglial density in the mPFC. The next analyses focused on the composition of the gut microbiome. CSC increased the abundance of Proteobacteria, which increases the risk for colitis. However, immunization had a stabilizing effect on overall gut microbiota and helped decrease risk for stress- and chemically-induced colitis. Finally, given findings that psychosocial stress decreases regulatory T cells in mice and humans, the effects of depleting these cells in immunized mice were studied. Treating mice with anti-CD25 (depleting Treg) had no effect on behavioral coping strategies or mRNA expression. However, it did prevent the immunization from reducing anxiety and spontaneous colitis.
This study mentions kynurenine, a molecule produced by breaking down tryptophan. Immunization in this study helped stabilize kynurenine. Kynurenine can be further broken down into kynurenic acid in astrocytes or quinolinic acid (QUIN) in microglia, both of which must be balanced in the body. An excess of QUIN can be neurotoxic. An excess of KYN has been linked to schizophrenic patient, especially their cognitive symptoms. I wonder if this connection to schizophrenia could be helpful in expanding this study to different mental illnesses, as this pathway could play a role in both stress-related disorders and schizophrenia. It would be interesting to study the effects of different microbes on the different parts of this pathway, specifically whether they affect KYN, QUIN, or tryptophan at its beginning. These effects would likely all manifest differently in patients.

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