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

This multidisciplinary study funded by the National Institutes of Health to investigate mechanisms linking vitamin D deficiency, gut permeability and microbial imbalance, inflammation, and risk of Alzheimer’s disease and related dementias (ADRD). The project focuses on determining how variations in bio-available vitamin D and disruptions of the gut microbiome contribute to adverse cognitive development and age-related cognitive decline, and whether these processes are compounded in people living with HIV. The research seeks to clarify biological pathways by which vitamin D supports immune function and modulates gene expression through the vitamin D receptor present in many tissues, including brain regions that influence cognition.

The team will explore how insufficient vitamin D may accelerate neuronal loss and ADRD progression by increasing inflammatory and oxidative stress processes in the brain. Parallel attention will examine gut microbial imbalance, a condition that worsens with age and can influence the brain via the gut–brain axis. Changes in the gut microbiome may perturb immune and endocrine signaling, promoting systemic and neuroinflammation that can hasten cognitive impairment. Because people with HIV often experience impaired immunity and gastrointestinal dysfunction, the investigators will assess whether HIV status interacts with vitamin D deficiency and gut dysbiosis to produce a compounded risk for cognitive decline. By integrating these elements, the study aims to identify modifiable biological targets—stabilizing gut health and addressing causes of vitamin D insufficiency—that could reduce inflammatory burden and ultimately lower ADRD risk or slow cognitive deterioration. 

The project’s design leverages interdisciplinary expertise spanning epidemiology, neuroscience, microbiology, nutrition and engineering to examine how immune modulation, microbial ecology and vitamin D biology intersect to influence cognitive trajectories. The investigators aim not only to delineate mechanistic links but also to inform interventions targeted at gut stabilization and correction of vitamin D deficits, particularly among HIV-affected populations who may face compounded vulnerability. Ultimately, the research intends to generate knowledge that can guide prevention strategies to mitigate ADRD risk across aging populations and in settings where HIV prevalence and nutritional and gut-health challenges converge.