Assessment of inflammatory pathways involved in the brain-intestinal axis in western diet induced Alzheimer's pathology

This research project on assessing inflammatory pathways involved in the brain–intestinal axis in Western diet–induced Alzheimer’s pathology focuses on the gut–brain axis and on prior studies examining how dietary components and lifestyle interventions influence gastrointestinal function and neurodegenerative disease processes.

The Al-Nakkash lab has a research history investigating the effects of genistein, a soy-derived phytoestrogen, and moderate exercise across clinically relevant models including cystic fibrosis, aging, Alzheimer’s disease, and diabetic obesity. That background positions the lab to interrogate how a Western diet—characterized by high fat and sugar content—may trigger or amplify inflammatory signaling between the gut and the brain, contributing to Alzheimer’s pathology. The project emphasizes mechanistic exploration of inflammatory pathways linking intestinal physiology and central nervous system outcomes, with particular attention to sex-dependent differences in response patterns.

By integrating the lab’s expertise in gastrointestinal function, dietary bioactives such as genistein, and the role of exercise, the research aims to delineate how peripheral inflammation and gut-derived signals influence neuroinflammation, synaptic integrity, and behavioral outcomes relevant to Alzheimer’s disease. The study leverages the Al-Nakkash lab’s broader programmatic interests—including medical education research and translational outreach activities—to ensure findings inform both basic science and community health perspectives. Dr. Al-Nakkash’s team has been supported by multiple funders across federal and private sectors, reflecting sustained investment in their multi-model, multidisciplinary approach to complex disease mechanisms.

The project’s outcomes are expected to advance understanding of how Western dietary patterns contribute to neurodegenerative processes via the gut–brain axis, identify sex-specific inflammatory signatures, and point to potential dietary, pharmacologic or lifestyle interventions that could mitigate risk or progression. Findings will be relevant to clinicians, researchers, and public health practitioners seeking to reduce Alzheimer’s disease burden by addressing modifiable systemic contributors.