Aging is the perhaps the greatest risk factor for the development of numerous health concerns, namely neurological diseases such as Alzheimer’s Disease (AD). Recently, certain variations in the gut microbiota have been implicated in the development of neurological disease. We hypothesize that alterations of the gut microbiome from age may cause dysregulated brain-gut communication, promoting inflammation and ultimately, disease. Indeed, our preliminary data found old mice to have a distorted gut microbiota, decreased cerebral blood flow and cognitive deficits, and distinct levels of certain brain metabolites than the young mice. The objective of this study was to examine the influence of the aging process on the brain-gut axis and how these collectively affect overall neurological function. We used a multi-disciplinary approach to address brain-gut interaction in reflection on brain physiology and cognitive function, including neuroimaging, 16s genomic sequencing of the gut microbiome, cognitive and behavioral testing, and brain metabolomic assessment.Male C57BL/6 mice were acquired from the National Institute of Aging Caloric Restriction Colony and assigned to two groups, Young (5-6 mo) and Old (18-20 mo), with 19-20 mice per group. This sample size was selected via a power analysis to ensure a comparison at a 0.05 level of significance and 90% chance of detecting a true difference in all measurements between the two groups. The Institutional Animal Care and Use Committee (IACUC) at the University of Kentucky according to NIH guidelines approved all experimental procedures. Cerebral blood flow was determined by magnetic resonance imaging (MRI) on a 7T Clinscan MR scanner in 8-10 mice per group. Fecal samples were collected from each mouse with subsequent DNA extraction for bacterial metagenomic analysis of 16S ribosomal RNA. Further, behavior and cognitive function was determined by radial arm water maze (RAWM) and novel object recognition (NOR). RAWM measured spatial working and reference memory while novel object recognition measured the behavior of mice via their affinity to explore new objects over familiar ones. Lastly, metabolomics profiling of the whole brain was assessed in a separate cohort of old and young mice (9 mice per group). Following sacrifice of the mice, their brains were sent to Metabolon (Durhan, NC) for analysis of biochemicals. Metabolon’s standard solvent extraction method was used to prepare the samples, which were then equally split for analysis via liquid chromatography/mass spectrometry (LC/MS) or gas chromatography/mass spectrometry (GC/MS). All statistical analyses were completed using GraphPad Prism (GraphPad, San Diego, CA, USA). One-tailed Student’s t-test was performed for determination of differences between groups. Levels of statistical significance were reached when p < 0.05.This experiment found many consequences of aging when comparing the old and young mice groups. Firstly, the old group demonstrated significantly reduced cerebral blood and variations in their gut micro biome. Next, the old mice demonstrated significantly compromised learning and behavioral performance in the RAWM and NOR. Lastly, the old mice saw modified metabolomic profiling of brain metabolites as markers of inflammation were significantly increased.The results of our study demonstrate the profound effects of aging, leading elderly individuals susceptible to disease. Our preliminary data indicate deleterious modifications of the gut microbiota, decreased cerebral blood flow, distorted cognitive function, and amplified markers of inflammation in old mice compared to that of young mice due to the aging process. Collectively, these modifications in the brain and gut indicate a dysfunctional brain-gut axis leading to, what we believe, increased inflammation and susceptibility to neurological disease. Remedying inflammation and modulating the gut microbiome may both be cheap yet effective treatment options in hopes to decrease the prevalence of neurological disorders. To conclude, our data indicates that age causes decreased cerebral blood flow, deleterious modifications of the gut microbiota, inhibited cognitive abilities, and amplified markers of inflammation in old mice compared to young mice. With this collective knowledge of the aging process, we can create better treatment options in hopes to manipulate and improve the brain-gut axis. In turn, this will decrease our susceptibility to neurological diseases, improving not only lifespan but the quality of life in humans.