PostbioticsSupplémentation postbiotique pour la santé intestinale et l'amélioration cognitive dans le trouble cognitif léger

This randomized, placebo-controlled clinical trial, known as the LpD3.5 Intervention Study in Older Adults (LISA), is designed to evaluate whether a heat-inactivated postbiotic of human origin (LpD3.5) can serve as a non-pharmacological intervention to reduce gut permeability and inflammation in older adults with mild cognitive impairment (MCI). The study will assess whether LpD3.5 supplementation can improve gut barrier function, microbiome characteristics, and health-related outcomes associated with cognitive decline. The primary objective of this study is to determine whether daily oral administration of dietary supplement-grade LpD3.5 (two capsules per day) reduces elevated gut permeability in older adults with MCI, as measured by plasma lipopolysaccharide-binding protein (LBP), a marker associated with intestinal barrier dysfunction. The secondary objective is to determine whether LpD3.5 supplementation improves gut-related factors, including fecal mucin levels and gut microbiome composition, and whether these changes are associated with reduced inflammation and improved cognitive function. Inflammatory markers in stool and blood, including calprotectin, C-reactive protein (CRP), IL-6, TNF-α, and IL-1β, as well as cognitive outcomes assessed using standardized cognitive measures, will be evaluated. Exploratory objectives include evaluating changes in blood pTau217 levels and examining potential relationships between LpD3.5 supplementation, gut permeability, microbiome alterations, inflammation, and cognitive function. The rationale for this study is based on growing evidence that age-related changes in the gut microbiome may contribute to increased intestinal permeability, chronic inflammation, and cognitive decline. Previous preclinical studies have demonstrated that heat-inactivated LpD3.5 improves gut barrier function, reduces inflammation, and enhances cognitive and metabolic outcomes in aging models. This clinical study will investigate whether these beneficial effects translate to older adults with MCI. Participants aged 60 years or older with clinically diagnosed MCI will be randomized to receive either LpD3.5 capsules or placebo capsules for 60 days, followed by a 30-day follow-up period. The study is designed to provide preliminary evidence regarding the safety, biological effects, and potential mechanisms of LpD3.5 as a dietary postbiotic intervention for improving gut health and related outcomes in older adults with MCI.