Assessing the therapeutic effect of probiotics in mild cognitive impairment individuals

Abstract

In this study, we investigated the therapeutic potential of probiotics in individuals with mild cognitive impairment (MCI), a clinical precursor to AD. Through in vitro screening and computational docking analysis, we assessed 13 probiotic strains for their capacity to inhibit the aggregation of Aβ and tau proteins. Four strains demonstrated significant antiaggregation properties, with Lactobacillus reuteri, L. paracasei, and L. rhamnosus emerging as the most effective in preventing Aβ42 oligomerization. Notably, lysed forms of these probiotics exhibited the strongest inhibitory effects on Aβ42 aggregation, suggesting that bacterial components or secreted metabolites may be key modulators. We further evaluated the efficacy of these probiotic strains in a randomized, double-blind, placebo-controlled clinical trial involving 40 MCI participants. Subjects were randomly assigned to receive either the probiotic formulation or a placebo over a seven-month intervention period. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) at baseline and post-intervention. While both groups exhibited some cognitive changes, a statistically significant improvement in MoCA scores was observed in the probiotic group (p < 0.001), indicating enhanced cognitive function associated with probiotic intake. This study provides compelling evidence that specific Lactobacillus probiotic strains can mitigate key pathological features of AD, particularly Aβ42 aggregation, through both direct molecular interaction and modulation of gut-brain axis signalling. The clinical findings support the potential of probiotic interventions to improve cognitive function in MCI patients. These findings warrant larger, multi-centre trials to validate the efficacy of probiotics as a non-invasive, adjunctive therapeutic strategy for delaying cognitive decline and potentially altering the course of neurodegenerative diseases such as AD.

Date of Thesis submission	2025
Original language	English
Awarding Institution	Western Sydney University
Sponsors	Australian Government Research Training Program Scholarship
Supervisor	Mourad Tayebi (Supervisor), Monique David (Supervisor), Patrick Adjei (Supervisor), Seth Amanquah (Supervisor) & Slade Jensen (Supervisor)