Gut permeability and variations in bio-available vitamin D as mechanisms of adverse cognitive development in HIV-affected & controls children - Anested Pilot Study

This multidisciplinary pilot study investigates how gut permeability and variability in bio-available vitamin D may contribute to adverse cognitive development and age-related cognitive decline, with particular attention to persons living with HIV. Backed by a $4 million NIH award, the project examines interconnected mechanisms — vitamin D deficiency, gut microbial imbalance, and inflammation — that plausibly accelerate neuronal loss and Alzheimer’s disease and related dementias (ADRD). Vitamin D acts broadly on immune function and gene regulation through the vitamin D receptor, including receptors located in brain regions key to cognition. Deficiency in vitamin D is associated with increased inflammation and oxidative stress, processes that can hasten neuronal death and progression toward ADRD. Parallel to this, age-related dysbiosis of the gut microbiome can exacerbate brain inflammation through the gut–brain axis, perturbing immune and endocrine signaling and promoting neuroinflammatory cascades.

People living with HIV often experience compromised immunity and gastrointestinal dysfunctions, creating a context in which vitamin D insufficiency and age-related microbial dysregulation might interact to compound cognitive risk. Implemented in Uganda, where Ezeamama has conducted research since 2018, the pilot study brings together expertise across MSU departments and external collaborators to characterize these pathways in a real-world, international setting. The interdisciplinary MSU team includes specialists in nursing and osteopathic medicine, biosystems and agricultural engineering, natural sciences, and translational neuroscience, and it engages regional partners such as the Uganda Society for Health Scientists and the Michigan Alzheimer’s Disease Research Center consortium.

The study aims to identify actionable targets to stabilize gut health, address the underlying contributors to vitamin D deficiency, and quantify the role of systemic and neural inflammation relative to HIV status in shaping cognitive outcomes. As a pilot, the research will generate preliminary data to clarify mechanisms linking micronutrient bioavailability and microbiome status to neurodegeneration, and to inform larger, definitive studies or interventions that could mitigate dementia risk. By integrating nutritional immunology, microbiome science, and neuroepidemiology, Ezeamama’s project seeks to elucidate modifiable biological pathways that may be especially relevant in vulnerable populations aging with HIV. The outcomes are intended to guide strategies for reducing inflammation, restoring gut balance, and ensuring adequate vitamin D bioavailability—approaches that might slow cognitive decline and reduce ADRD incidence in diverse global populations.