Probiotic Milk Drink for Gut and Brain Health in Older Adults and Caregivers

This pilot clinical trial will investigate the effects of a human-origin probiotic fermented milk (PFM) beverage on biological pathways related to gut and brain health in individuals with Alzheimer's disease and related dementias (ADRD) and their caregivers. The study is based on evidence suggesting that alterations in the gut microbiome, nutrient metabolism, and systemic inflammation may be associated with cognitive and behavioral health and may represent modifiable targets in ADRD. Participants with ADRD and their caregivers will be enrolled as patient-caregiver dyads and independently randomized to receive either the PFM intervention or a matched placebo for 30 days. The PFM contains four human-origin probiotic strains: Limosilactobacillus reuteri HL278, Lactiplantibacillus plantarum HL279, Lacticaseibacillus paracasei HL260, and Lactiplantibacillus plantarum HL82. Biological assessments will be performed before and after the intervention to characterize changes in the gut microbiome, nutrient-related measures, and systemic inflammation. Fecal microbiome composition will be evaluated using metagenomic sequencing and bioinformatics approaches to examine microbial diversity and taxonomic composition. Blood- and stool-based laboratory analyses will be used to assess selected nutrient and inflammatory biomarkers. Clinical and behavioral measures will also be evaluated to explore whether biological changes associated with the intervention are related to measures of health, quality of life, agitation, stress, or anxiety in participants with ADRD and their caregivers. Analyses will compare changes between the PFM and placebo groups and explore relationships among microbiome characteristics, nutrient-related measures, inflammatory markers, and behavioral outcomes. The study is intended to generate preliminary information regarding the biological effects and feasibility of the PFM intervention and to provide data that may inform the design of larger future clinical trials.