A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer’s-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics

Abstract

Background: The brain-gut-microbiome axis has emerged as an important pathway through which perturbations in the gut and/or microbial microenvironment can impact neurological function. Such alterations have been implicated in a variety of neuropsychiatric disorders, includ- ing depression, anxiety, and Alzheimer’s Disease (AD) and the use of probiotics as therapy for th- ese diseases remains promising. However, the mechanisms underlying the gut microenvironment’s influence on disease pathogenesis and therapy remain unclear. Objective: The objective of this study is to investigate the effect of a novel probiotic formula, BIOCG, on cognitive function and pathobiological mechanisms, including amyloid processing and dendritic spine dynamics, in a mouse model of AD. Methods: BIOCG was administered for 3 months to 3xTg or 3xTg; Thy1-YFP AD mice and func- tional outcomes were assessed via behavioral testing and electrophysiology. Mechanisms relevant to AD pathogenesis including dendritic spine morphology and turnover, Amyloid Precursor Pro- tein (APP) processing and microglial phenotype were also evaluated. Finally, we sequenced fecal samples following probiotic treatment to assess the impact on gut microbial composition and corre- late the changes with the above described measures. Results: Mice treated with BIOCG demonstrated preserved cognitive abilities and stronger Long- Term Potentiation (LTP), spontaneous Excitatory Postsynaptic Currents (sEPSC), and glutamate-in- duced LTPs, indicative of functional and electrophysiological effects. Moreover, we observed atten- uated AD pathogenesis, including reduced Amyloid Beta (Aβ) burden, as well as more mature den- dritic spines in the BIOCG-treated. Our finding of changes in microglial number and phenotype in the treatment group suggests that this formulation may mediate its effects via attenuation of neu- roinflammation. Sequencing data confirmed that the gut microbiome in treated mice was more varied and harbored a greater proportion of “beneficial” bacteria. Conclusion: Overall, our results indicate that treatment with BIOCG enhances microbial diversity and, through gut-brain axis interactions, attenuates neuroinflammation to produce histologic and functional improvement in AD pathogenesis.

The Impact of Probiotic Supplementation on Cognitive, Pathological and Metabolic Markers in a Transgenic Mouse Model of Alzheimer’s Disease

“…In support of these findings, we observed higher transcript levels of NSMF, a regulator of the DNA repair response ( Ju et al, 2021 ), and BDNF that is involved in neuronal survival in the whole brain extracts of the mice receiving Lab4b to the Control group. A recent study of Sun M. et al (2021) demonstrated the ability of another probiotic to increase spine densities in the cortex of 3xTg-AD mice. Our own studies have also shown beneficial effects of probiotics on neuronal health in vitro with Lab4b demonstrating an ability to prevent loss of viability in human SH-SY5Y neurones exposed to neurotoxic challenge ( Michael et al, 2019 ).…”

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