Probiotic effects on brain health are both transient and sustained for several weeks after discontinuation: a randomised controlled trial

Abstract Background Modulating the gut-brain axis via probiotic supplementation has emerged as attractive strategy to promote brain health, but its long-term effects are largely unknown. Methods This study with 32 community-dwelling self-reported healthy older adults (68.0 ± 5.4 years, 21 f/11 m, without contraindications for study examinations) assesses whether probiotic effects persist after intake cessation using brain imaging, targeting function (exploratory outcome of main study, primary outcome of report) and structure, and questionnaires for psychological assessments (exploratory). The 4-6 weeks discontinuation follow-up was performed after assessing immediate effects of a six-week randomised, blinded (investigators, nurses, participants), placebo-controlled parallel trial with two different formulations of Lacticaseibacillus rhamnosus HN001 of identical appearance/taste, in autumn 2023 in Örebro, Sweden. Results Trial status: completed; participants analysed (of randomised) per group: n = 8(29) encapsulated probiotic, n = 12(31) non-encapsulated probiotic, n = 12(30) placebo; no related adverse events at discontinuation follow-up. Previously reported immediate intervention effects evoked alteration in anxiety symptom scores and distinct resting state functional connectivity patterns. While some changes persisted, others were not detectable any longer at discontinuation follow-up. Comparing both probiotic formulations, connectivity between left superior parietal lobule and right occipital/cuneal/intracalcarine/supracalcarine cortex differed significantly (seed-to-voxel analysis, T = + 7.38, cluster-size p = 0.0001 FDR-corrected, additionally correct for number of tests); levels for Hospital Anxiety and Depression Scale Total Score and its Anxiety Subscore differed significantly (time*group interaction effects); both between weeks 10-12 and week 6, but not baseline. Conclusions These findings suggest that some brain-related probiotic effects may indeed persist 4-6 weeks post-intervention cessation, especially on the level of brain function as indicated by resting state functional connectivity, suggesting longer-lasting gut-brain axis effects than previously presumed. Registration ClinicalTrials.gov NCT05801042.