TARGETING AGE-RELATED NEURODEGENERATION THROUGH GUT–BRAIN AXIS MODULATION: THE ORPHEA STUDY

The preclinical ORPHEA study evaluates an innovative synbiotic strategy combining selected probiotic strains with gamma-oryzanol (ORY) to promote healthy aging and counteract age-related cognitive decline. ORY is a multifunctional bioactive compound extracted from sustainable sources such as rice bran, a by-product of rice processing industries.
The study was conducted using the SAMP8 mouse model together with its control strain, SAMR1. SAMP8 mice exhibit accelerated senescence and spontaneously develop key features of Alzheimer's disease (AD), including progressive cognitive impairment, amyloid-beta deposition, tau hyperphosphorylation, and neuroinflammation, making them a valuable tool for investigating age-related neurodegeneration. Following two months of administration with probiotics or ORY alone, or their synbiotic combination, stool collection and behavioural assessments were performed. Multiplexed ELISA and immunohistochemistry were conducted to investigate neurodegeneration and inflammation markers, alongside AD pathological hallmarks including p-Tau, total Tau, and Aβ oligomeric forms in the hippocampus and other brain regions. Microbiota composition analysis was also performed.
Administration of the synbiotic formulation significantly improved cognitive performance. Beneficial effects were also observed with ORY alone or the probiotic mix alone, suggesting both independent and synergistic mechanisms. Histological and molecular analyses revealed modulation of key biomarkers involved in neurodegenerative pathways, indicating potential neuroprotective effects. Ongoing analyses aim to further evaluate disease-associated marker levels to elucidate the underlying mechanisms of the synbiotic intervention.
The ORPHEA study supports the hypothesis that targeting the gut-brain axis through combined nutritional and microbiota-modulating interventions represents a promising therapeutic approach to delay or mitigate neurodegenerative processes associated with aging.