Metagenomics data analysis to unravel the impact of high-fat diet on the development of affective disorders through immune-microbiome interactions

Abstract

The gut-brain axis is defined as the bidirectional communication between the brain and the microorganisms present in the gastrointestinal tract. This interaction modulates several brain functions, including behavior, through the production of neuroactive molecules and gene expression regulation. Therefore, disturbances in the gut microbiota are associated with behavior changes, immune dysregulation, neuroinflammation and microglial activation. Considering that different psychiatric disorders share common characteristics of this disturbance, such as reduced anti-inflammatory cytokines and increased pro-inflammatory cytokines, the aim of this project is to unravel how microbiota disturbances by high-fat diet influence the immune system and the central nervous system. Thus, metagenome sequencing data from fecal samples of mice groups fed with control and high-fat diets will be analyzed by bioinformatics approaches. Firstly, KneadData will be used to perform quality control on FASTQ files. Then, phylogenetics composition will be profiled by MetaPhlAn 4.0, which will be used as input for the functional analysis by HUMAnN3. Several QIIME2 plugins will be used to further investigate the metagenomes, as, for instance, machine learning algorithms to find features that best discriminate between the two diet groups or that are related to brain or behavior changes. Consequently, molecules, pathways and bacterias differentially abundant between the two groups will be obtained. Therefore, this project will help determine microorganisms and metabolites that modulate cognitive and mood functions, which is necessary to develop effective adjuvant therapies for debilitating psychiatric conditions, including Bipolar Disorder, Major Depressive Disorder and Schizophrenia. (AU)