Micro-encapsulation differentially impacts probiotic effects on brain structure and function in an elderly population – A randomised placebo-controlled trial

• Lacticaseibacillus rhamnosus affects brain connectivity in older adults. • Encapsulated and non-encapsulated probiotic differentially affect brain connectivity. • Lacticaseibacillus rhamnosus supplementation altered brain morphometry. • Brain imaging offers novel tools to assess the gut-brain axis and healthy ageing. Increasing evidence suggests that modulations of the gut-brain axis with probiotics impact healthy ageing. This double-blinded, randomised, placebo-controlled study compared effects of micro-encapsulated and non-encapsulated Lacticaseibacillus rhamnosus HN001 in 87 community-dwelling elderly (60–80 years). Resting state functional connectivity differed significantly in regions involved in visual processing and perception between the two probiotic groups (p < 0.0001). Brain morphometry was not altered. Significant time*group effects (p < 0.05) were observed for processing speed, non-significant effects were observed for short-term memory and anxiety symptoms, while other cognitive domains, depression, perceived stress, and sleep quality were unaffected. Distribution of available and stored peripheral serotonin was significantly affected (p < 0.05), while levels of γ-aminobutyric acid and glutamate in striatum and circulating brain-derived neurotrophic factor did not show significant time*group effects. Micro-encapsulated probiotics target the gut differently, which impacts the effects on brain health assessed by (functional) magnetic resonance imaging in older adults. The trial is registered at ClinicalTrials.gov under ID: NCT05801042.