Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach

It is well established that the gut-brain axis (GBA) is a bidirectional communication between the gut and the brain. This axis, critical in maintaining overall homeostasis, is regulated at the neuronal, endocrine, and immunological levels, all of which may be influenced by the gut microbiota (GM). Therefore, dysbiosis or disruption in the GM may have serious consequences including neuroinflammation due to overactivation of the immune system. Strategies to reestablish GM integrity via use of probiotics are being pursued as novel therapeutic intervention in a variety of central and peripheral diseases. The mechanisms leading to dysbiosis or efficacy of probiotics, however, are not fully evident. Here, we performed computational analysis on two major probiotics, namely <i>Lactobacillus Lacticaseibacillus rhamnosus</i> GG (formerly named <i>Lactobacillus rhamnosus</i>, <i>L. rhamnosus</i> GG) and <i>Bifidobacterium animalis</i> spp. <i>lactis (B. lactis</i> or <i>B. animalis)</i> to not only shed some light on their mechanism(s) of action but also to identify potential molecular targets for novel probiotics. Using the PubMed web page and BioCyc Database Collection platform we specifically analyzed proteins affected by metabolites of these bacteria. Our results indicate that peroxisome proliferator-activated receptors (PPARs), nuclear receptor proteins that are involved in regulation of inflammation are key mediators of the neuroactive effect of probiotics.