The impact of the Lab4 probiotic on neurodegenerative processes in a murine Alzheimer’s disease model

Introduction The gut-brain-axis is increasingly recognised as a mediator of neurodegenerative processes, with the gut microbiota emerging as a potential target for intervention. The Lab4 probiotic has demonstrated neuroprotective activity in vitro and, here, we have investigated its impact on aspects of neurodegeneration in the 3xTg Alzheimer’s disease (AD) murine model. Method Male 3xTg-AD mice were fed a high fat diet (to accelerate neurodegeneration) with or without daily Lab4 probiotic supplementation for 84 days. Endpoints included hippocampal neuronal spine density, novel object recognition, whole-brain gene expression, plasma cytokines/lipids, body weight, and faecal microbiota composition. Results Lab4 Probiotic supplementation preserved the neuronal spine density, particularly thin spines, and improved recognition memory. Gene expression analysis of whole brain extracts detected reductions in pro-inflammatory markers (IL-5 and Caspase-1) and plasma analysis revealed reduced levels of pro-inflammatory TNF- α . The probiotic also mitigated weight gain, though plasma lipid profiles were unchanged. Microbiota analysis indicated increased abundance of Blautia and decreased Muribaculaceae in probiotic-supplemented mice, alongside reduced numbers of viable yeast. Discussion These preliminary findings highlight a neuroprotective impact in 3xTg-AD mice receiving the Lab4 probiotic and warrant more extensive assessments in murine models and/or human subjects.