Abstract: Alzheimer’s Disease (AD) etiology remains unclear. As the gut microbiota has been linked to neurological disorders development, its role in the insurgence and progression of this disease is under close scrutiny. We present an untargeted metabolomics dataset (n=2,271) acquired from 3xTg and 5xFAD animals, complemented by shotgun metagenomics sequencing data (n=666). This public resource includes biological samples collected from 5 different tissue types, under diverse colonization conditions, and genotypic backgrounds. Systems-level analysis revealed clusters of dysregulated molecules across tissues including carnitines, bile acids, B vitamins, and neurotransmitters. This signature, coupled with microbial data, points to increased oxidative stress via mitochondrial dysfunction in AD. Molecular feature tracking via tissueMASST, a mass spectrometry search tool developed to contextualize animal findings in human data, identified the microbially-modulated phenylacetyl-carnitine across multiple human AD datasets, in which it correlates with age and cognitive decline. With more molecules left to be discovered, this public resource and its associated tools will aid future investigations in the field of Alzheimer’s Disease research.
This repository houses the data, notebooks, analyses, and figures related to the microbiome analysis of the published resource paper (Figure 6, S9) [doi info here]